Nitric Oxide and the Vascular Endothelium

Part of the Handbook of Experimental Pharmacology book series (HEP, volume 176/I)

Abstract

The vascular endothelium synthesises the vasodilator and anti-aggregatory mediator nitric oxide (NO) from L-arginine. This action is catalysed by the action of NO synthases, of which two forms are present in the endothelium. Endothelial (e)NOS is highly regulated, constitutively active and generates NO in response to shear stress and other physiological stimuli. Inducible (i)NOS is expressed in response to immunological stimuli, is transcriptionally regulated and, once activated, generates large amounts of NO that contribute to pathological conditions. The physiological actions of NO include the regulation of vascular tone and blood pressure, prevention of platelet aggregation and inhibition of vascular smooth muscle proliferation. Many of these actions are a result of the activation by NO of the soluble guanylate cyclase and consequent generation of cyclic guanosine monophosphate (cGMP). An additional target of NO is the cytochrome c oxidase, the terminal enzyme in the electron transport chain, which is inhibited by NO in a manner that is reversible and competitive with oxygen. The consequent reduction of cytochrome c oxidase leads to the release of superoxide anion. This may be an NO-regulated cell signalling system which, under certain circumstances, may lead to the formation of the powerful oxidant species, peroxynitrite, that is associated with a variety of vascular diseases.

Keywords

Nitric oxide eNOS Guanylate cyclase Cytochrome c oxidase Mitochondria Free radicals 

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References

  1. Abu Soud HM, Stuehr DJ (1993) Nitric oxide synthases reveal a role for calmodulin in controlling electron transfer. Proc Natl Acad Sci USA 90:10769–10772PubMedGoogle Scholar
  2. Adak S, Wang Q, Stuehr DJ (2000) Arginine conversion to nitroxide by tetrahydrobiopterin-free neuronal nitric oxide synthase. J Biol Chem 275:33554–33561PubMedGoogle Scholar
  3. Ahn KY, Mohaupt MG, Madsen KM, et al. (1994) In situ hybridization localization of mRNA encoding inducible nitric oxide synthase in rat kidney. Am J Physiol 267:F748–F757PubMedGoogle Scholar
  4. Albina JE (1995) On the expression of nitric oxide synthase by human macrophages. Why no NO? J Leukoc Biol 58:643–649PubMedGoogle Scholar
  5. Alderton WK, Cooper CE, Knowles RG (2001) Nitric oxide synthases: structure, function and inhibition. Biochem J 357:593–615PubMedGoogle Scholar
  6. Alderton WK, Angell AD, Craig C, et al. (2005) GW274150 and GW273629 are potent and highly selective inhibitors of inducible nitric oxide synthase in vitro and in vivo. Br J Pharmacol 145:301–312PubMedGoogle Scholar
  7. Aliev G, Bodin P, Burnstock G (1998) Free radical generators cause changes in endothelial and inducible nitric oxide synthases and endothelin-1 immunoreactivity in endothelial cells from hyperlipidemic rabbits. Mol Genet Metab 63:191–197PubMedGoogle Scholar
  8. Aoyagi M, Arvai AS, Tainer JA, et al. (2003) Structural basis for endothelial nitric oxide synthase binding to calmodulin. EMBO J 22:766–775PubMedGoogle Scholar
  9. Arnet UA, McMillan A, Dinerman JL, et al. (1996) Regulation of endothelial nitric oxide synthase during hypoxia. J Biol Chem 271:15069–15073PubMedGoogle Scholar
  10. Asselbergs FW, van der Harst P, Jessurun GAJ, et al. (2005) Clinical impact of vasomotor function assessment and the role of ACE-inhibitors and statins. Vascul Pharmacol 42:125–140PubMedGoogle Scholar
  11. Ayajiki K, Kindermann M, Hecker M, et al. (1996) Intracellular pH and tyrosine phosphorylation but not calcium determine shear stress-induced nitric oxide production in native endothelial cells. Circ Res 78:750–758PubMedGoogle Scholar
  12. Azadzoi KM, Master TA, Siroky MB (2004) Effect of chronic ischemia on constitutive and inducible nitric oxide synthase expression in erectile tissue. J Androl 25:382–388PubMedGoogle Scholar
  13. Azuma H, Ishikawa M, Sekizaki S (1986) Endothelium-dependent inhibition of platelet aggregation. Br J Pharmacol 88:411–415PubMedGoogle Scholar
  14. Baek KJ, Thiel BA, Lucas S, et al. (1993) Macrophage nitric oxide synthase subunits. Purification, characterization, and role of prosthetic groups and substrate in regulating their association into a dimeric enzyme. J Biol Chem 268:21120–21129PubMedGoogle Scholar
  15. Balligand JL, Kelly RA, Marsden PA, et al. (1993) Control of cardiac muscle cell function by an endogenous nitric oxide signaling system. Proc Natl Acad Sci USA 90:347–351PubMedGoogle Scholar
  16. Barbacanne MA, Rami J, Michel JB, et al. (1999) Estradiol increases rat aorta endothelium-derived relaxing factor (EDRF) activity without changes in endothelial NO synthase gene expression: possible role of decreased endothelium-derived superoxide anion production. Cardiovasc Res 41:672–681PubMedGoogle Scholar
  17. Barbato JE, Tzeng E (2004) Nitric oxide and arterial disease. J Vasc Surg 40:187–193PubMedGoogle Scholar
  18. Barouch LA, Harrison RW, Skaf MW, et al. (2002) Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms. Nature 416:337–339PubMedGoogle Scholar
  19. Bates TE, Loesch A, Burnstock G, et al. (1995) Immunocytochemical evidence for a mitochondrially located nitric oxide synthase in brain and liver. Biochem Biophys Res Commun 213:896–900PubMedGoogle Scholar
  20. Bauer PM, Fulton D, Boo YC (2003) Compensatory phosphorylation and protein-protein interactions revealed by loss of function and gain of function mutants of multiple serine phosphorylation sites in endothelial nitric oxide synthase. J Biol Chem 278:14841–14849PubMedGoogle Scholar
  21. Bauersachs J, Fleming I, Scholz D, et al. (1997) Endothelium-derived hyperpolarizing factor, but not nitric oxide, is reversibly inhibited by brefeldin A. Hypertension 30:1598–1605PubMedGoogle Scholar
  22. Beckman JS, Beckman TW, Chen J, et al. (1990) Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 87:1620–1624PubMedGoogle Scholar
  23. Beierwaltes WH, Potter DL, Shesely EG (2002) Renal baroreceptor-stimulated renin in the eNOS knockout mouse. Am J Physiol 282:F59–F64Google Scholar
  24. Beltran B, Orsi A, Clementi E, et al. (2000) Oxidative stress and S-nitrosylation of proteins in cells. Br J Pharmacol 129:953–960PubMedGoogle Scholar
  25. Benjafield AV, Morris BJ (2000) Association analyses of endothelial nitric oxide synthase gene polymorphisms in essential hypertension. Am J Hypertens 13:994–998PubMedGoogle Scholar
  26. Berkels R, Stockklauser K, Rosen P, et al. (1997) Current status of platelet NO synthases. Thromb Res 87:51–55PubMedGoogle Scholar
  27. Bernal-Mizrachi C, Gates AC, Weng S, et al. (2005) Vascular respiratory uncoupling increases blood pressure and atherosclerosis. Nature 435:502–506PubMedGoogle Scholar
  28. Biffl WL, Moore EE, Moore FA, et al. (1996) Nitric oxide reduces endothelial expression of intercellular adhesion molecule (ICAM)-1. J Surg Res 63:328–332PubMedGoogle Scholar
  29. Blatter LA, Wier WG (1994) Nitric oxide decreases [Ca2+]i in vascular smooth muscle by inhibition of the calcium current. Cell Calcium 15:122–131PubMedGoogle Scholar
  30. Blot S, Arnal JF, Xu Y, et al. (1994) Spinal cord infarcts during long-term inhibition of nitric oxide synthase in rats. Stroke 25:1666–1673PubMedGoogle Scholar
  31. Boger RH, Bode-Boger SM, Szuba A, et al. (1998) Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation 98:1842–1847PubMedGoogle Scholar
  32. Bolotina VM, Najibi S, Palacino JJ, et al. (1994) Nitric oxide directly activates calciumdependent potassium channels in vascular smooth muscle. Nature 368:850–853PubMedGoogle Scholar
  33. Boo YC, Jo H (2003) Flow-dependent regulation of endothelial nitric oxide synthase: role of protein kinases. Am J Physiol 285:C499–C508Google Scholar
  34. Boo YC, Sorescu G, Boyd N, et al. (2002) Shear stress stimulates phosphorylation of endothelial nitric-oxide synthase at Ser1179 by Akt-independent mechanisms: role of protein kinase A. J Biol Chem 277:3388–3396PubMedGoogle Scholar
  35. Boo YC, Sorescu GP, Bauer PM, et al. (2003) Phosphorylation of eNOS at Ser635 stimulates NO production in a Ca2+-independent manner. FASEB J 17:A805Google Scholar
  36. Bouloumie A, Schini-Kerth VB, Busse R (1999) Vascular endothelial growth factor upregulates nitric oxide synthase expression in endothelial cells. Cardiovasc Res 41:773–780PubMedGoogle Scholar
  37. Boutin JA (1997) Myristoylation. Cell Commun Signal 9:15–35Google Scholar
  38. Bowen R, Haslam RJ (1991) Effects of nitrovasodilators on platelet cyclic nucleotide levels in rabbit blood; role for cyclic AMP in synergistic inhibition of platelet function by SIN-1 and prostaglandin E1. J Cardiovasc Pharmacol 17:424–433PubMedGoogle Scholar
  39. Brandes RP, Schmitz-Winnenthal FH, Feletou M, et al. (2000) An endothelium-derived hyperpolarizing factor distinct from NO and prostacyclin is a major endothelium-dependent vasodilator in resistance vessels of wild-type and endothelial NO synthase knockout mice. Proc Natl Acad Sci USA 97:9747–9752PubMedGoogle Scholar
  40. Bredt DS, Snyder SH (1990) Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc Natl Acad Sci USA 87:682–685PubMedGoogle Scholar
  41. Bredt DS, Hwang PM, Glatt CE, et al. (1991) Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase. Nature 351:714–718PubMedGoogle Scholar
  42. Brouet A, Sonveaux P, Dessy C, et al. (2001) Hsp90 and caveolin are key targets for the proangiogenic nitric oxide-mediated effects of statins. Circ Res 89:866–873PubMedGoogle Scholar
  43. Brown GC (1999) Nitric oxide and mitochondrial respiration. Biochim Biophys Acta 1411:351–369PubMedGoogle Scholar
  44. Brown GC, Cooper CE (1994) Nanomolar concentrations of nitric oxide reversibly inhibit synaptosomal respiration by competing with oxygen at cytochrome oxidase. FEBS Lett 356:295–298PubMedGoogle Scholar
  45. Bucci M, Gratton JP, Rudic RD, et al. (2000) In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation. Nat Med 6:1362–1367PubMedGoogle Scholar
  46. Busconi L, Michel T (1993) Endothelial nitric oxide synthase: N-terminal myristoylation determines subcellular localization. J Biol Chem 268:8410–8413PubMedGoogle Scholar
  47. Busse R, Mulsch A (1990) Calcium-dependent nitric oxide synthesis in endothelial cytosol is mediated by calmodulin. FEBS Lett 265:133–136PubMedGoogle Scholar
  48. Buttery LD, Springall DR, Chester AH, et al. (1996) Inducible nitric oxide synthase is present within human atherosclerotic lesions and promotes the formation and activity of peroxynitrite. Lab Invest 75:77–85PubMedGoogle Scholar
  49. Cai H, Harrison DG (2000) Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 87:840–844PubMedGoogle Scholar
  50. Cai H, Davis ME, Drummond GR, et al. (2001) Induction of endothelial NO synthase by hydrogen peroxide via a Ca2+/calmodulin-dependent protein kinase II/janus kinase 2-dependent pathway. Arterioscler Thromb Vasc Biol 21:1571–1576PubMedGoogle Scholar
  51. Cao S, Yao J, Shah V (2003) The proline-rich domain of dynamin-2 is responsible for dynamin-dependent in vitro potentiation of endothelial nitric oxide synthase activity via selective effects on reductase domain function. J Biol Chem 278:5894–5901PubMedGoogle Scholar
  52. Carr A, Frei B (2000) The role of natural antioxidants in preserving the biological activity of endothelium-derived nitric oxide. Free Radic Biol Med 28:1806–1814PubMedGoogle Scholar
  53. Caulin-Glaser T, Garcia-Cardena G, Sarrel P, et al. (1997) 17 β-Estradiol regulation of human endothelial cell basal nitric oxide release, independent of cytosolic Ca2+ mobilization. Circ Res 81:885–892PubMedGoogle Scholar
  54. Chambliss KL, Shaul PW (2002) Rapid activation of endothelial NO synthase by estrogen: evidence for a steroid receptor fast-action complex (SRFC) in caveolae. Steroids 67:413–419PubMedGoogle Scholar
  55. Chance B, Sies B, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59:527–605PubMedGoogle Scholar
  56. Charles IG, Palmer RM, Hickery MS, et al. (1993) Cloning, characterization, and expression of a cDNA encoding an inducible nitric oxide synthase from the human chondrocyte. Proc Natl Acad Sci USA 90:11419–11423PubMedGoogle Scholar
  57. Chartrain NA, Geller DA, Koty PP, et al. (1994) Molecular cloning, structure and chromosomal localization of the human inducible nitric oxide synthase gene. J Biol Chem 269:6765–6772PubMedGoogle Scholar
  58. Chen LY, Mehta JL (1996) Further evidence of the presence of constitutive and inducible nitric oxide synthase isoforms in human platelets. J Cardiovasc Pharmacol 27:154–158PubMedGoogle Scholar
  59. Chen ZP, Mitchelhill KI, Michell BJ, et al. (1999) AMP-activated protein kinase phosphorylation of endothelial NO synthase. FEBS Lett 443:285–289PubMedGoogle Scholar
  60. Choi YB, Lipton SA (2000) Redox modulation of the NMDA receptor. Cell Mol Life Sci 57:1535–1541PubMedGoogle Scholar
  61. Chowdhary S, Townend JN (1999) Role of nitric oxide in the regulation of cardiovascular autonomic control. Clin Sci (Lond) 97:5–17PubMedGoogle Scholar
  62. Cieslik K, Abrams CS, Wu KK (2001) Up-regulation of endothelial nitric-oxide synthase promoter by the phosphatidylinositol 3-kinase gamma/Janus kinase 2/MEK-1-dependent pathway. J Biol Chem 276:1211–1219PubMedGoogle Scholar
  63. Cleeter MW, Cooper JM, Darley-Usmar VM, et al. (1994) Reversible inhibition of cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, by nitric oxide. Implications for neurodegenerative diseases. FEBS Lett 345:50–54PubMedGoogle Scholar
  64. Clementi E, Brown GC, Feelisch M, et al. (1998) Persistent inhibition of cell respiration by nitric oxide: crucial role of S-nitrosylation of mitochondrial complex I and protective action of glutathione. Proc Natl Acad Sci USA 95:7631–7636PubMedGoogle Scholar
  65. Clementi E, Brown GC, Foxwell N, et al. (1999) On the mechanism by which vascular endothelial cells regulate their oxygen consumption. Proc Natl Acad Sci USA 96:1559–1562PubMedGoogle Scholar
  66. Cohen RA (2005) The endothelium-derived hyperpolarizing factor puzzle. A mechanism without a mediator? Circulation 111:724–727PubMedGoogle Scholar
  67. Cooke JP (2003) NO and angiogenesis. Atheroscler Suppl 4:53–60PubMedGoogle Scholar
  68. Cornwell TL, Pryzwansky KB, Wyatt TA, et al. (1991) Regulation of sarcoplasmic reticulum protein phosphorylation by localized cyclic GMP-dependent protein kinase in vascular smooth muscle cells. Mol Pharmacol 40:923–931PubMedGoogle Scholar
  69. Crane BR, Arvai AS, Gachhui R, et al. (1997) The structure of nitric oxide synthase oxygenase domain and inhibitor complexes. Science 278:425–431PubMedGoogle Scholar
  70. Cromheeke KM, Kockx MM, De Meyer GR, et al. (1999) Inducible nitric oxide synthase colocalizes with signs of lipid oxidation/peroxidation in human atherosclerotic plaques. Cardiovasc Res 43:744–754PubMedGoogle Scholar
  71. Cubberley RR, Alderton WK, Boyhan A, et al. (1997) Cysteine-200 of human inducible nitric oxide synthase is essential for dimerization of haem domains and for binding of haem, nitroarginine and tetrahydrobiopterin. Biochem J 323:131–146Google Scholar
  72. D’Uscio LV, Milstien S, Richardson D, et al. (2003) Long-termvitamin C treatment increases vascular tetrahydrobiopterin levels and nitric oxide synthase activity. Circ Res 92:88–95PubMedGoogle Scholar
  73. Daff S, Sagami I, Shimizu T (1999) The 42-amino acid insert in the FMN domain of neuronal nitric-oxide synthase exerts control over Ca(2+)/calmodulin-dependent electron transfer. J Biol Chem 274:30589–30595PubMedGoogle Scholar
  74. Davis ME, Grumbach IM, Fukai T, et al. (2004) Shear stress regulates endothelial nitricoxide synthase promoter activity through nuclear factor kappaB binding. J Biol Chem 279:163–168PubMedGoogle Scholar
  75. De Caterina R, Libby P, Peng HB, et al. (1995) Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J Clin Invest 96:60–68PubMedGoogle Scholar
  76. Dedio J, Konig P, Wohlfart P, et al. (2001) NOSIP, a novel modulator of endothelial nitric oxide synthase activity. FASEB J 15:79–89PubMedGoogle Scholar
  77. De Meyer GR, Kockx MM, Cromheeke KM, et al. (2000) Periadventitial inducible nitric oxide synthase expression and intimal thickening. Arterioscler Thromb Vasc Biol 20:1896–1902PubMedGoogle Scholar
  78. De Meyer GR, De Cleen DM, Cooper S, et al. (2002) Platelet phagocytosis and processing of beta-amyloid precursor protein as a mechanism of macrophage activation in atherosclerosis. Circ Res 90:1197–1204PubMedGoogle Scholar
  79. Denninger JW, Marletta MA (1999) Guanylate cyclase and the NO/cGMP signaling pathway. Biochim Biophys Acta 1411:334–350PubMedGoogle Scholar
  80. Dimmeler S, Fleming I, Fisslthaler B, et al. (1999) Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 399:601–605PubMedGoogle Scholar
  81. Ding H, Kubes P, Triggle C (2000) Potassium-and acetylcholine-induced vasorelaxation in mice lacking endothelial nitric oxide synthase. Br J Pharmacol 129:1194–1200PubMedGoogle Scholar
  82. Djordjevic S, Roberts DL, Wang M (1995) Crystallization and preliminary X-ray studies of NADPH-cytochrome P450 reductase. Proc Natl Acad Sci USA 92:3214–3218PubMedGoogle Scholar
  83. Dobrucki LW, Kalinowski L, Dobrucki IT, et al. (2001) Statin-stimulated nitric oxide release from endothelium. Med Sci Monit 7:622–627PubMedGoogle Scholar
  84. Dunphy JT, Linder ME (1998) Signalling functions of protein palmitoylation. Biochem Biophys Acta 1436:245–261PubMedGoogle Scholar
  85. Durante W, Schini VB, Scott-Burden T, et al. (1991) Platelet inhibition by an L-argininederived substance released by IL-1 beta-treated vascular smooth muscle cells. Am J Physiol 261:H2024–H2030PubMedGoogle Scholar
  86. Endres M, Laufs U, Huang Z, et al. (1998) Stroke protection by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase. Proc Natl Acad Sci USA 95:8880–8885PubMedGoogle Scholar
  87. Esaki T, Hayashi T, Muto E, et al. (1997) Expression of inducible nitric oxide synthase in T lymphocytes and macrophages of cholesterol-fed rabbits. Atherosclerosis 128:39–46PubMedGoogle Scholar
  88. Fard A, Tuck CH, Donis JA, et al. (2000) Acute elevations of plasma asymmetric dimethylarginine and impaired endothelial function in response to a high-fat meal in patients with type 2 diabetes. Arterioscler Thromb Vasc Biol 20:2039–2044PubMedGoogle Scholar
  89. Feng Y, Venema VJ, Venema RC, et al. (1999) VEGF-induced permeability increase is mediated by caveolae. Invest Ophthalmol Vis Sci 40:157–167PubMedGoogle Scholar
  90. Feron O, Saldana F, Michel JB, et al. (1998) The endothelial nitric oxide synthase-caveolin regulatory cycle. J Biol Chem 273:3125–3128PubMedGoogle Scholar
  91. Feron O, Dessy C, Moniotte S, et al. (1999) Hypercholesterolemia decreases nitric oxide production by promoting the interaction of caveolin and endothelial nitric oxide synthase. J Clin Invest 103:897–905PubMedGoogle Scholar
  92. Fichtlscherer S, Dimmeler S, Breuer S, et al. (2004) Inhibition of cytochrome P450 2C9 improves endothelium-dependent, nitric oxide-mediated vasodilatation in patients with coronary artery disease. Circulation 109:178–183PubMedGoogle Scholar
  93. Fischmann TO, Hruza A, Niu XD, et al. (1999) Structural characterization of nitric oxide synthase isoforms reveals striking active-site conservation. Nat Struct Biol 6:233–242PubMedGoogle Scholar
  94. Fisslthaler B, Dimmeler S, Hermann C, et al. (2000) Phosphorylation and activation of the endothelial nitric oxide synthase by fluid shear stress. Acta Physiol Scand 168:81–88PubMedGoogle Scholar
  95. Fisslthaler B, Benzing T, Busse R, et al. (2003) Insulin enhances the expression of the endothelial nitric oxide synthase in native endothelial cells: a dual role for Akt and AP-1. Nitric Oxide 8:253–261PubMedGoogle Scholar
  96. Fleming I (2001) Cytochrome p450 and vascular homeostasis. Circ Res 89:753–762PubMedGoogle Scholar
  97. Fleming I, Busse R (2003) Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase. Am J Physiol 284:R1–R12Google Scholar
  98. Fleming I, Fisslthaler B, Dimmeler S, et al. (2001) Phosphorylation of Thr495 regulates Ca2+/calmodulin-dependent endothelial nitric oxide synthase activity. Circ Res 88:e68–e75PubMedGoogle Scholar
  99. Fleming I, Schulz C, Fichtlscherer B, et al. (2003) AMP-activated protein kinase (AMPK) regulates the insulin-induced activation of the nitric oxide synthase in human platelets. Thromb Haemost 90:863–871PubMedGoogle Scholar
  100. Fliser D (2005) Asymmetric dimethylarginine (ADMA): the silent transition from an ‘uraemic toxin’ to a global cardiovascular risk molecule. Eur J Clin Invest 35:71–79PubMedGoogle Scholar
  101. Förstermann U, Pollock JS, Schmidt HH, et al. (1991) Calmodulin-dependent endotheliumderived relaxing factor/nitric oxide synthase activity is present in the particulate and cytosolic fractions of bovine aortic endothelial cells. Proc Natl Acad Sci USA 88:1788–1792PubMedGoogle Scholar
  102. Förstermann U, Closs EI, Pollock JS, et al. (1994) Nitric oxide synthase isozymes. Characterization, purification, molecular cloning and functions. Hypertension 23:1121–1131PubMedGoogle Scholar
  103. Freedman JE, Sauter R, Battinelli EM, et al. (1999) Deficient platelet-derived nitric oxide and enhanced hemostasis in mice lacking the NOSIII gene. Circ Res 84:1416–1421PubMedGoogle Scholar
  104. Frost MT, Wang Q, Moncada S, et al. (2005) Hypoxia accelerates nitric oxide-dependent inhibition of mitochondrial complex I in activated macrophages. Am J Physiol 288:R394–R400Google Scholar
  105. Fukuchi M, Giaid A (1999) Endothelial expression of endothelial nitric oxide synthase and endothelin-1 in human coronary artery disease. Specific reference to underlying lesion. Lab Invest 79:659–670PubMedGoogle Scholar
  106. Fulton D, Gratton JP, McCabe TJ, et al. (1999) Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature 399:597–601PubMedGoogle Scholar
  107. Fulton D, Babbitt R, Zoellner S, et al. (2004) Targeting of endothelial nitric oxide synthase to the cytoplasmic face of the golgi complex or plasma membrane regulates Akt-versus calcium-dependent mechanisms for nitric oxide release. J Biol Chem 279:30349–30357PubMedGoogle Scholar
  108. Fung HL (2004) Biochemical mechanism of nitroglycerin action and tolerance: is this old mystery solved? Annu Rev Pharmacol Toxicol 44:67–85PubMedGoogle Scholar
  109. Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376PubMedGoogle Scholar
  110. Gaboury J, Woodman RC, Granger DN, et al. (1993) Nitric oxide prevents leukocyte adherence: role of superoxide. Am J Physiol 265:H862–H867PubMedGoogle Scholar
  111. Gao S, Chen J, Brodsky SV, et al. (2004) Docking of endothelial nitric oxide synthase (eNOS) to the mitochondrial outer membrane: a pentabasic amino acid sequence in the autoinhibitory domain of eNOS targets a proteinase K-cleavable peptide on the cytoplasmic face of mitochondria. J Biol Chem 279:15968–15974PubMedGoogle Scholar
  112. Garcia-Cardena G, Oh P, Liu J, et al. (1996) Targeting of nitric oxide synthase to endothelial cell caveolae via palmitoylation: implications for nitric oxide signaling. Proc Natl Acad Sci USA 93:6448–6453PubMedGoogle Scholar
  113. Garcia-Cardena G, Fan R, Shah V, et al. (1998) Dynamic activation of endothelial nitric oxide synthase by Hsp90. Nature 392:821–824PubMedGoogle Scholar
  114. Garg UC, Hassid A (1989) Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest 83:1774–1777PubMedGoogle Scholar
  115. Gauthier TW, Davenpeck KL, Lefer AM (1994) Nitric oxide attenuates leukocyte-endothelial interaction via P-selectin in splanchnic ischemia-reperfusion. Am J Physiol 267:G562–G568PubMedGoogle Scholar
  116. Geiger J, Nolte C, Walter U (1994) Regulation of calcium mobilization and entry in human platelets by endothelium-derived factors. Am J Physiol 267:C236–C244PubMedGoogle Scholar
  117. Geller DA, Lowenstein CJ, Shapiro RA, et al. (1993) Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes. Proc Natl Acad Sci USA 90:3491–3495PubMedGoogle Scholar
  118. Gewaltig MT, Kojda G (2002) Vasoprotection by nitric oxide: mechanisms and therapeutic potential. Cardiovasc Res 55:250–260PubMedGoogle Scholar
  119. Ghafourifar P, Richter C (1997) Nitric oxide synthase activity in mitochondria. FEBS Lett 418:291–296PubMedGoogle Scholar
  120. Giulivi C, Poderoso JJ, Boveris A (1998) Production of nitric oxide by mitochondria. J Biol Chem 273:11038–11043PubMedGoogle Scholar
  121. Go YM, Park H, Maland MC, et al. (1998) Phosphatidylinositol 3-kinase β mediates shear stress-dependent activation of JNK in endothelial cells. Am J Physiol 275:H1898–H1904PubMedGoogle Scholar
  122. Go YM, Gipp JJ, Mulcahy RT, et al. (2004) H2O2-dependent activation of GCLC-ARE4 reporter occurs by mitogen-activated protein kinase pathways without oxidation of cellular glutathione or thioredoxin-1. J Biol Chem 279:5837–5845PubMedGoogle Scholar
  123. Govers R, Rabelink TJ (2001) Cellular regulation of endothelial nitric oxide synthase. Am J Physiol Renal Physiol 280:F193–F206PubMedGoogle Scholar
  124. Govers R, van der Sluijs P, van Donselaar E, et al. (2002) Endothelial nitric oxide synthase and its negative regulator caveolin-1 localize to distinct perinuclear organelles. J Histochem Cytochem 50:779–788PubMedGoogle Scholar
  125. Gow AJ, Stamler JS (1998) Reactions between nitric oxide and haemoglobin under physiological conditions. Nature 391:169–173PubMedGoogle Scholar
  126. Gratton JP, Fontana J, O’Connor DS, et al. (2000) Reconstitution of an endothelial nitric oxide synthase (eNOS), hsp90, and caveolin-1 complex in vivo. J Biol Chem 275:22268–22272PubMedGoogle Scholar
  127. Greenacre SA, Ischiropoulos H (2001) Tyrosine nitration: localization, quantification, consequences for protein function and signal transduction. Free Radic Res 34:541–581PubMedGoogle Scholar
  128. Grisham MB, Jourd’Heuil D, Wink DA (1999) Nitric oxide. I. Physiological chemistry ofnitric oxide and its metabolites: implications in inflammation. Am J Physiol 276:G315–G321PubMedGoogle Scholar
  129. Hagen T, Taylor CT, Lam F, et al. (2003) Redistribution of intracellular oxygen in hypoxia by nitric oxide: effect on HIF1α. Science 302:1975–1978PubMedGoogle Scholar
  130. Harris MB, Ju H, Venema VJ, et al. (2001) Reciprocal phosphorylation and regulation of endothelial nitric oxide synthase in response to bradykinin stimulation. J Biol Chem 276:16587–16591PubMedGoogle Scholar
  131. Hattori Y, Nakanishi N, Kasai K (2002) Statin enhances cytokine-mediated induction of nitric oxide synthesis in vascular smooth muscle cells. Cardiovasc Res 54:649–658PubMedGoogle Scholar
  132. Heitzer T, Yla-Herttuala S, Luoma J, et al. (1996) Cigarette smoking potentiates endothelial dysfunction of forearm resistance vessels in patients with hypercholesterolemia. Role of oxidized LDL. Circulation 93:1346–1353PubMedGoogle Scholar
  133. Hernandez-Perera O, Perez-Sala D, Navarro-Antolin J, et al. (1998) Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells. J Clin Invest 101:2711–2719PubMedGoogle Scholar
  134. Hess DT, Matsumoto A, Kim SO, et al. (2005) Protein S-nitrosylation: purview and parameters. Nat Rev Mol Cell Biol 6:150–166PubMedGoogle Scholar
  135. Hibbs JB, Taintor RR, Vavrin Z, et al. (1990) Synthesis of nitric oxide from a terminal guanidine nitrogen atom of L-arginine: a molecular mechanism regulating cellular proliferation that targets intracellular iron. In: Moncada S, Higgs EA (eds) Nitric oxide from L-arginine: a bioregulatory system. Elsevier, Amsterdam, pp 189–223Google Scholar
  136. Hingorani AD, Liang CF, Fatibene J, et al. (1999) A common variant of the endothelial nitric oxide synthase (Glu298Asp) is a major risk factor for coronary artery disease in the UK. Circulation 100:1515–1520PubMedGoogle Scholar
  137. Hink U, Li H, Mollnau H, et al. (2001) Mechanisms underlying endothelial dysfunction in diabetes mellitus. Circ Res 88:E14–E22PubMedGoogle Scholar
  138. Hobbs AJ, Higgs A, Moncada S (1999) Inhibition of nitric oxide synthase as a potential therapeutic target. Annu Rev Pharmacol Toxicol 39:191–220PubMedGoogle Scholar
  139. Hood JD, Meininger CJ, Ziche M, et al. (1998) VEGF upregulates ecNOS message, protein, and NO production in human endothelial cells. Am J Physiol 274:H1054–H1058PubMedGoogle Scholar
  140. Hoyer J, Köhler R, Distler A (1998) Mechanosensitive Ca2+ oscillations and STOC activation in endothelial cells. FASEB J 12:359–366PubMedGoogle Scholar
  141. Huang A, Sun D, Koller A, et al. (1998) Gender difference in flow-induced dilation and regulation of shear stress: role of estrogen and nitric oxide. Am J Physiol 275:R1571–R1577PubMedGoogle Scholar
  142. Huang A, Sun D, Carroll MA, et al. (2001) EDHF mediates flow-induced dilation in skeletal muscle arterioles of female eNOS-KO mice. Am J Physiol 280:H2462–H2469Google Scholar
  143. Huang PL, Huang Z, Mashimo H, et al. (1995) Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature 377:239–242PubMedGoogle Scholar
  144. Inoue N, Venema RC, Sayegh HS, et al. (1995) Molecular regulation of the bovine endothelial cell nitric oxide synthase by transforming growth factor-beta 1. Arterioscler Thromb Vasc Biol 15:1255–1261PubMedGoogle Scholar
  145. Ito A, Tsao PS, Adimoolam S, et al. (1999) Novel mechanism for endothelial dysfunction: dysregulation of dimethylarginine dimethylaminohydrolase. Circulation 99:3092–3095PubMedGoogle Scholar
  146. Jaffrey SR, Erdjument-Bromage H, Ferris CD, et al. (2001) Protein S-nitrosylation: a physiological signal for neuronal nitric oxide. Nat Cell Biol 3:193–197PubMedGoogle Scholar
  147. Janssens S, Flaherty D, Nong Z, et al. (1998) Human endothelial nitric oxide synthase gene transfer inhibits vascular smooth muscle cell proliferation and neointima formation after balloon injury in rats. Circulation 97:1274–1281PubMedGoogle Scholar
  148. Janssens SP, Shimouchi A, Quertermous T, et al. (1992) Cloning and expression of a cDNA encoding human endothelium-derived relaxing factor/nitric oxide synthase. J Biol Chem 267:14519–14522PubMedGoogle Scholar
  149. Jenkins DC, Charles IG, Thomsen LL, et al. (1995) Roles of nitric oxide in tumor growth. Proc Natl Acad Sci USA 92:4392–4396PubMedGoogle Scholar
  150. Jiang J, Cyr D, Babbitt RW, et al. (2003) Chaperone-dependent regulation of endothelial nitric oxide synthase intracellular trafficking by the co-chaperone/ubiquitin ligase CHIP. J Biol Chem 278:49332–49341PubMedGoogle Scholar
  151. Jobin CM, Chen H, Lin AJ, et al. (2003) Receptor-regulated dynamic interaction between endothelial nitric oxide synthase and calmodulin revealed by fluorescence resonance energy transfer in living cells. Biochemistry 42:11716–11725PubMedGoogle Scholar
  152. Kanai AJ, Pearce LL, Clemens PR, et al. (2001) Identification of a neuronal nitric oxide synthase in isolated cardiac mitochondria using electrochemical detection. Proc Natl Acad Sci USA 98:14126–14131PubMedGoogle Scholar
  153. Kanwar S, Kubes P (1995) Nitric oxide is an antiadhesive molecule for leukocytes. New Horiz 3:93–104PubMedGoogle Scholar
  154. Karantzoulis-Fegaras F, Antoniou H, Lai SL, et al. (1999) Characterization of the human endothelial nitric-oxide synthase promoter. J Biol Chem 274:3076–3093PubMedGoogle Scholar
  155. Khan BV, Harrison DG, Olbrych MT, et al. (1996) Nitric oxide regulates vascular cell adhesion molecule 1 gene expression and redox-sensitive transcriptional events in human vascular endothelial cells. Proc Natl Acad Sci USA 93:9114–9119PubMedGoogle Scholar
  156. Kilbourn RG, Jubran A, Gross SS, et al. (1990) Reversal of endotoxin-mediated shock by NG-methyl-L-arginine, an inhibitor of nitric oxide synthesis. Biochem Biophys Res Commun 172:1132–1138PubMedGoogle Scholar
  157. Kim JW, Kang KW, Oh GT, et al. (2002) Induction of hepatic inducible nitric oxide synthase by cholesterol in vivo and in vitro. Exp Mol Med 34:137–144PubMedGoogle Scholar
  158. Kimura S, Zhang GX, Nishiyama A (2005) Mitochondria-derived reactive oxygen species and vascular MAP kinases: comparison of angiotensin II and diazoxide. Hypertension 45:438–444PubMedGoogle Scholar
  159. Knowles RG, Palacios M, Palmer RMJ, et al. (1989) Formation of nitric oxide from L-arginine in the central nervous system: a transduction mechanism for stimulation of the soluble guanylate cyclase. Proc Natl Acad Sci USA 86:5159–5162PubMedGoogle Scholar
  160. Knowles RG, Salter M, Brooks SL, et al. (1990) Anti-inflammatory glucocorticoids inhibit the induction by endotoxin of nitric oxide synthase in the lung, liver and aorta of the rat. Biochem Biophys Res Commun 172:1042–1048PubMedGoogle Scholar
  161. Kobzik L, Stringer B, Balligand JL, et al. (1995) Endothelial type nitric oxide synthase in skeletal muscle fibers: mitochondrial relationships. Biochem Biophys Res Commun 211:375–381PubMedGoogle Scholar
  162. Kojda G, Cheng YC, Burchfield J, et al. (2001) Dysfunctional regulation of endothelial nitric oxide synthase (eNOS) expression in response to exercise in mice lacking one eNOS gene. Circulation 103:2839–2844PubMedGoogle Scholar
  163. Korhonen R, Lahti A, Hamalainen M, et al. (2002) Dexamethasone inhibits inducible nitric oxide synthase expression and nitric oxide production by destabilizing mRNA in lipopolysaccharide-treated macrophages. Mol Pharmacol 62:698–704PubMedGoogle Scholar
  164. Kroll J, Waltenberger J (1998) VEGF-A induces expression of eNOS and iNOS in endothelial cells via VEGF receptor-2 (KDR). Biochem Biophys Res Commun 252:743–746PubMedGoogle Scholar
  165. Kubes P (1995) Nitric oxide affects microvascular permeability in the intact and inflamed vasculature. Microcirculation 2:235–244PubMedGoogle Scholar
  166. Kubes P, Suzuki M, Granger DN (1991) Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci USA 88:4651–4655PubMedGoogle Scholar
  167. Kuhlencordt PJ, Gyurko R, Han F, et al. (2001a) Accelerated atherosclerosis, aortic aneurysm formation, and ischemic heart disease in apolipoprotein E/endothelial nitric oxide synthase double-knockout mice. Circulation 104:448–454PubMedGoogle Scholar
  168. Kuhlencordt PJ, Chen J, Han F, et al. (2001b) Genetic deficiency of inducible nitric oxide synthase reduces atherosclerosis and lowers plasma lipid peroxides in apolipoprotein E-knockout mice. Circulation 103:3099–3104PubMedGoogle Scholar
  169. Kuhlencordt PJ, Rosel E, Gerszten RE, et al. (2004) Role of endothelial nitric oxide synthase in endothelial activation: insights from eNOS knockout endothelial cells. Am J Physiol 286:C1195–C1202Google Scholar
  170. Kureishi Y, Luo Z, Shiojima I, et al. (2000) The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med 6:1004–1010PubMedGoogle Scholar
  171. Kurihara N, Alfie ME, Sigmon DH, et al. (1998) Role of nNOS in blood pressure regulation in eNOS null mutant mice. Hypertension 32:856–861PubMedGoogle Scholar
  172. Kurtz A, Wagner C (1998) Role of nitric oxide in the control of renin secretion. Am J Physiol 275:F849–F862PubMedGoogle Scholar
  173. Lablanche JM, Grollier G, Lusson JR, et al. (1997) Effect of the direct nitric oxide donors linsidomine and molsidomine on angiographic restenosis after coronary balloon angioplasty. The ACCORD Study. Angioplastic Coronaire Corvasal Diltiazem. Circulation 95:83–89PubMedGoogle Scholar
  174. Lamas S, Marsden PA, Li GK, et al. (1992) Endothelial nitric oxide synthase: molecular cloning and characterization of a distinct constitutive enzyme isoform. Proc Natl Acad Sci USA 89:6348–6352PubMedGoogle Scholar
  175. Landmesser U, Dikalov S, Price SR, et al. (2003) Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension. J Clin Invest 111:1201–1209PubMedGoogle Scholar
  176. Lane P, Gross SS (2002) Disabling a C-terminal autoinhibitory control element in endothelial nitric-oxide synthase by phosphorylation provides a molecular explanation for activation of vascular NO synthesis by diverse physiological stimuli. J Biol Chem 277:19087–19094PubMedGoogle Scholar
  177. Lane P, Hao G, Gross SS (2001) S-nitrosylation is emerging as a specific and fundamental post-translational protein modification: head-to-head comparison with O-phosphorylation. Sci STKE 86:RE1Google Scholar
  178. Lantoine F, Brunet A, Bedioui F, et al. (1995) Direct measurement of nitric oxide production in platelets: relationship with cytosolic Ca2+ concentration. Biochem Biophys Res Commun 215:842–848PubMedGoogle Scholar
  179. Laszlo F, Whittle BJR, Moncada S (1994) Time-dependent enhancement or inhibition of endotoxin-induced vascular injury in rat intestine by nitric oxide synthase inhibitors. Br J Pharmacol 111:1309–1315PubMedGoogle Scholar
  180. Laufs U, Fata VL, Liao JK (1997) Inhibition of 3-hydroxy-methylglutaryl (HMG)-CoA reductase blocks hypoxia-mediated down-regulation of endothelial nitric oxide synthase. J Biol Chem 272:31725–31729PubMedGoogle Scholar
  181. Leibovich SJ, Polverini PJ, Fong TW, et al. (1994) Production of angiogenic activity by human monocytes requires an L-arginine/nitric oxide-synthase-dependent effector mechanism. Proc Natl Acad Sci USA 91:4190–4194PubMedGoogle Scholar
  182. Leiper JM, Santa Maria J, Chubb A, et al. (1999) Identification of two human dimethylarginine dimethylaminohydrolases with distinct tissue distributions and homology with microbial arginine deiminases. Biochem J 343:209–214PubMedGoogle Scholar
  183. Leopold JA, Loscalzo J (2005) Oxidative enzymopathies and vascular disease. Arterioscler Thromb Vasc Biol 25:1332–1340PubMedGoogle Scholar
  184. Levine GN, Frei B, Koulouris SN, et al. (1996) Ascorbic acid reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation 93:1107–1113PubMedGoogle Scholar
  185. Lin MI, Fulton D, Babbitt R, et al. (2003) Phosphorylation of threonine 497 in endothelial nitric oxide synthase coordinates the coupling of L-arginine metabolism to efficient nitric oxide production. J Biol Chem 278:44719–44726PubMedGoogle Scholar
  186. Liu J, Garcia Cardena G, Sessa WC (1995) Biosynthesis and palmitoylation of endothelial nitric oxide synthase: mutagenesis of palmitoylation sites, cysteines-15 and/or-26, argues against depalmitoylation-induced translocation of the enzyme. Biochemistry 34:12333–12340PubMedGoogle Scholar
  187. Liu J, Hughes TE, Sessa WC (1997) The first 35 amino acids and fatty acylation sites determine the molecular targeting of endothelial nitric oxide synthase into the golgi region of cells: a green fluorescent protein study. J Cell Biol 137:1525–1535PubMedGoogle Scholar
  188. Lopez-Ongil S, Hernandez-Perera O, Navarro-Antolin J, et al. (1998) Role of reactive oxygen species in the signalling cascade of cyclosporine A-mediated up-regulation of eNOS in vascular endothelial cells. Br J Pharmacol 124:447–454PubMedGoogle Scholar
  189. Lu JL, Schmiege LM 3rd, Kuo L, et al. (1996) Downregulation of endothelial constitutive nitric oxide synthase expression by lipopolysaccharide. Biochem Biophys Res Commun 225:1–5PubMedGoogle Scholar
  190. Lu TM, Ding YA, Charng MJ, et al. (2003) Asymmetrical dimethylarginine: a novel risk factor for coronary artery disease. Clin Cardiol 26:458–464PubMedGoogle Scholar
  191. Luckhoff A, Pohl U, Mulsch A, et al. (1988) Differential role of extra-and intracellular calcium in the release of EDRF and prostacyclin from cultured endothelial cells. Br J Pharmacol 95:189–196PubMedGoogle Scholar
  192. Luo Z, Fujio Y, Kureishi Y, et al. (2000) Acute modulation of endothelial Akt/PKB activity alters nitric oxide-dependent vasomotor activity in vivo. J Clin Invest 106:493–499PubMedGoogle Scholar
  193. Luoma JS, Stralin P, Marklund SL, et al. (1998) Expression of extracellular SOD and iNOS in macrophages and smooth muscle cells in human and rabbit atherosclerotic lesions: colocalization with epitopes characteristic of oxidized LDL and peroxynitrite-modified proteins. Arterioscler Thromb Vasc Biol 18:157–167PubMedGoogle Scholar
  194. Luscher TF, Tanner FC, Tschudi MR, et al. (1993) Endothelial dysfunction in coronary artery disease. Annu Rev Med 44:395–418PubMedGoogle Scholar
  195. MacNaul KL, Hutchinson NI (1993) Differential expression of iNOS and cNOS mRNA in human vascular smooth muscle cells and endothelial cells under normal and inflammatory conditions. Biochem Biophys Res Commun 196:1330–1334PubMedGoogle Scholar
  196. Malinski T, Radomski MW, Taha Z, et al. (1993) Direct electrochemical measurement of nitric oxide released from human platelets. Biochem Biophys Res Commun 194:960–965PubMedGoogle Scholar
  197. Mann GE, Yudilevich DL, Sobrevia L (2003) Regulation of amino acid and glucose transporters in endothelial and smooth muscle cells. Physiol Rev 83:183–252PubMedGoogle Scholar
  198. Mannick JB, Hausladen A, Liu L, et al. (1999) Fas-induced caspase denitrosylation. Science 284:651–654PubMedGoogle Scholar
  199. Marrero MB, Venema VJ, Ju H, et al. (1999) Endothelial nitric oxide synthase interactions with G-protein-coupled receptors. Biochem J 343:335–340PubMedGoogle Scholar
  200. Marsden PA, Shappert KT, Chen HS, et al. (1992) Molecular cloning and characterization of human endothelial nitric oxide synthase. FEBS Lett 307:287–293PubMedGoogle Scholar
  201. Marsden PA, Heng HH, Scherer SW, et al. (1993) Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J Biol Chem 268:17478–17488PubMedGoogle Scholar
  202. Massberg S, Sausbier M, Klatt P, et al. (1999) Increased adhesion and aggregation of platelets lacking cyclic guanosine 3′,5′-monophosphate kinase I. J Exp Med 189:1255–1264PubMedGoogle Scholar
  203. Massion PB, Feron O, Dessy C, et al. (2003) Nitric oxide and cardiac function: ten years after, and continuing. Circ Res 93:388–398PubMedGoogle Scholar
  204. Matsumura M, Kakishita H, Suzuki M, et al. (2001) Dexamethasone suppresses iNOS gene expression by inhibiting NF-κB in vascular smooth muscle cells. Life Sci 69:1067–1077PubMedGoogle Scholar
  205. Mattson DL, Bellehumeur TG (1996) Neural nitric oxide synthase in the renal medulla and blood pressure regulation. Hypertension 28:297–303PubMedGoogle Scholar
  206. Mattson DL, Lu S, Cowley AW Jr (1997) Role of nitric oxide in the control of the renal medullary circulation. Clin Exp Pharmacol Physiol 24:587–590PubMedGoogle Scholar
  207. Maxwell AJ (2002) Mechanisms of dysfunction of the nitric oxide pathway in vascular diseases. Nitric Oxide 6:101–124PubMedGoogle Scholar
  208. McCabe TJ, Fulton D, Roman LJ, et al. (2000) Enhanced electron flux and reduced calmodulin dissociation may explain “calcium-independent” eNOS activation by phosphorylation. J Biol Chem 275:6123–6128PubMedGoogle Scholar
  209. Mete A, Connolly S (2003) Inhibitors of the NOS enzymes: a patent review. I Drugs 6:57–65PubMedGoogle Scholar
  210. Michel T, Gordon K, Busconi L (1993) Phosphorylation and subcellular translocation of endothelial nitric oxide synthase. Proc Natl Acad Sci USA 90:6252–6256PubMedGoogle Scholar
  211. Michell BJ, Chen Z, Tiganis T, et al. (2001) Coordinated control of endothelial NO synthase phosphorylation by protein kinase C and the cAMP-dependent protein kinase. J Biol Chem 276:17625–17628PubMedGoogle Scholar
  212. Mitchell JA, Förstermann U, Warner TD, et al. (1991) Endothelial cells have a particulate enzyme system responsible for EDRF formation: measurement by vascular relaxation. Biochem Biophys Res Commun 176:1417–1423PubMedGoogle Scholar
  213. Miyamoto Y, Saito Y, Kajiyama N, et al. (1998) Endothelial nitric oxide synthase gene is positively associated with essential hypertension. Hypertension 32:3–8PubMedGoogle Scholar
  214. Moncada S (1989) Introduction. In: Moncada S, Higgs EA (eds) Nitric oxide from L-arginine: a bioregulatory system. Elsevier, Amsterdam, pp 1–4Google Scholar
  215. Moncada S (2006) Adventures in vascular biology: a tale of two mediators. Phil Trans Roy Soc B 361:735–759Google Scholar
  216. Moncada S, Erusalimsky JD (2002) Does nitric oxide modulate mitochondrial energy generation and apoptosis? Nat Rev Mol Cell Biol 3:214–220PubMedGoogle Scholar
  217. Moncada S, Higgs EA (2006) The discovery of nitric oxide and its role in vascular biology. Br J Pharmacol 147:S193–S201PubMedGoogle Scholar
  218. Moncada S, Palmer RM, Higgs EA (1989) Biosynthesis of nitric oxide from L-arginine. A pathway for the regulation of cell function and communication. Biochem Pharmacol 38:1709–1715PubMedGoogle Scholar
  219. Moncada S, Palmer RMJ, Higgs EA (1991) Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev 43:109–142PubMedGoogle Scholar
  220. Moroi M, Zhang L, Yasuda T, et al. (1998) Interaction of genetic deficiency of endothelial nitric oxide, gender, and pregnancy in vascular response to injury in mice. J Clin Invest 101:1225–1232PubMedGoogle Scholar
  221. Morris SM Jr, Billiar TR (1994) New insights into the regulation of inducible nitric oxide synthesis. Am J Physiol 266:E829–E839PubMedGoogle Scholar
  222. Mueller CF, Laude K, McNally JS, et al. (2005) Redox mechanisms in blood vessels. Arterioscler Thromb Vasc Biol 25:274–278PubMedGoogle Scholar
  223. Munzel T, Kurz S, Heitzer T, et al. (1996) New insights into mechanisms underlying nitrate tolerance. Am J Cardiol 77:24C–30CPubMedGoogle Scholar
  224. Muruganandam A, Mutus B (1994) Isolation of nitric oxide synthase from human platelets. Biochim Biophys Acta 1200:1–6PubMedGoogle Scholar
  225. Nagareddy PR, Xia Z, McNeill JH, et al. (2005) Increased expression of iNOS is associated with endothelial dysfunction and impaired pressor responsiveness in streptozotocin-induced diabetes. Am J Physiol Heart Circ Physiol 289:H2144–H2152PubMedGoogle Scholar
  226. Nakane M, Schmidt HH, Pollock JS, et al. (1993) Cloned human brain nitric oxide synthase is highly expressed in skeletal muscle. FEBS Lett 316:175–180PubMedGoogle Scholar
  227. Nakayama T, Soma M, Takahashi Y, et al. (1997) Association analysis of CA repeat polymorphism of the endothelial nitric oxide synthase gene with essential hypertension in Japanese. Clin Genet 51:26–30PubMedGoogle Scholar
  228. Nathan C, Xie QW (1994) Nitric oxide synthases: roles, tolls and controls. Cell 78:915–918PubMedGoogle Scholar
  229. Navarro J, Sanchez A, Saiz J, et al. (1994) Hormonal, renal and metabolic alterations during hypertension induced by chronic inhibition of NO in rats. Am J Physiol 267:R1516–R1521PubMedGoogle Scholar
  230. Navarro-Antolin J, Rey-Campos J, Lamas S (2000) Transcriptional induction of endothelial nitric oxide gene by cyclosporine A. A role for activator protein-1. J Biol Chem 275:3075–3080PubMedGoogle Scholar
  231. Nedvetsky PI, Sessa WC, Schmidt HH (2002) There’s NO binding like NOS binding: protein-protein interactions in NO/cGMP signaling. Proc Natl Acad Sci USA 99:16510–16512PubMedGoogle Scholar
  232. Neunteufl T, Heher S, Katzenschlager R, et al. (2000) Late prognostic value of flow-mediated dilation in the brachial artery of patients with chest pain. Am J Cardiol 86:207–210PubMedGoogle Scholar
  233. Nishida CR, Ortiz de Montellano PR (1999) Autoinhibition of endothelial nitric-oxide synthase. Identificationof an electrontransfer control element. J Biol Chem 274:14692–14698PubMedGoogle Scholar
  234. Nishida K, Harrison DG, Navas JP, et al. (1992) Molecular cloning and characterization of the constitutive bovine aortic endothelial cell nitric oxide synthase. J Clin Invest 90:2092–2096PubMedGoogle Scholar
  235. Nisoli E, Clementi E, Paolucci C, et al. (2003) Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide. Science 299:896–899PubMedGoogle Scholar
  236. Nisoli E, Tonello C, Cardile A, et al. (2005) Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science 310:314–317PubMedGoogle Scholar
  237. Ohashi Y, Kawashima S, Hirata K, et al. (1998) Hypotension and reduced nitric oxide-elicited vasorelaxation in transgenic mice overexpressing endothelial nitric oxide synthase. J Clin Invest 102:2061–2071PubMedGoogle Scholar
  238. Ortiz PA, Garvin JL (2003) Cardiovascular and renal control in NOS-deficient mouse models. Am J Physiol 284:R628–R638Google Scholar
  239. Ortiz PA, Hong NJ, Garvin JL (2001) NO decreases thick ascending limb chloride absorption by reducing Na+-K+-2Cl-cotransporter activity. Am J Physiol 281:F819–F825Google Scholar
  240. Palacios-Callender M, Quintero M, Hollis VS, et al. (2004) Endogenous NO regulates superoxide production at low oxygen concentrations by modifying the redox state of cytochrome c oxidase. Proc Natl Acad Sci USA 101:7630–7635PubMedGoogle Scholar
  241. Pallone TL, Mattson DL (2002) Role of nitric oxide in regulation of the renal medulla in normal and hypertensive kidneys. Curr Opin Nephrol Hypertens 11:93–98PubMedGoogle Scholar
  242. Palmer RM, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327:524–526PubMedGoogle Scholar
  243. Palmer RM, Ashton DS, Moncada S (1988) Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 333:664–666PubMedGoogle Scholar
  244. Palmer RMJ, Moncada S (1989) A novel citrulline-forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells. Biochem Biophys Res Commun 158:348–352PubMedGoogle Scholar
  245. Papapetropoulos A, Garcia-Cardena G, Madri JA, et al. (1997) Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells. J Clin Invest 100:3131–3139PubMedGoogle Scholar
  246. Paulus WJ, Shah AM (1999) NO and cardiac diastolic function. Cardiovasc Res 43:595–606PubMedGoogle Scholar
  247. Pelligrino DA, Ye S, Tan F, et al. (2000) Nitric oxide-dependent pial arteriolar dilation in the female rat: effects of chronic estrogen depletion and repletion. Biochem Biophys Res Commun 269:165–171PubMedGoogle Scholar
  248. Perez-Mato I, Castro C, Ruiz FA, et al. (1999) Methionine adenosyltransferase S-nitrosylation is regulated by the basic and acidic amino acids surrounding the target thiol. J Biol Chem 274:17075–17079PubMedGoogle Scholar
  249. Persichini T, Mazzone V, Polticelli F, et al. (2005) Mitochondrial type I nitric oxide synthase physically interacts with cytochrome c oxidase. Neurosci Lett 384:254–259PubMedGoogle Scholar
  250. Petroff MG, Kim SH, Pepe S, et al. (2001) Endogenous nitric oxide mechanisms mediate the stretch dependence of Ca2+ release in cardiomyocytes. Nat Cell Biol 3:867–873PubMedGoogle Scholar
  251. Pfeifer A, Klatt P, Massberg S, et al. (1998) Defective smooth muscle regulation in cGMP kinase I-deficient mice. EMBO J 17:3045–3051PubMedGoogle Scholar
  252. Poderoso JJ, Carreras MC, Lisdero C, et al. (1996) Nitric oxide inhibits electron transfer and increases superoxide radical production in rat heart mitochondria and submitochondrial particles. Arch Biochem Biophys 328:85–92PubMedGoogle Scholar
  253. Pollock JS, Förstermann U, Mitchell JA, et al. (1991) Purification and characterization of particulate endothelium-derived relaxing factor synthase from cultured and native bovine aortic endothelial cells. Proc Natl Acad Sci USA 88:10480–10484PubMedGoogle Scholar
  254. Pollock JS, Klinghofer V, Förstermann U, et al. (1992) Endothelial nitric oxide synthase is myristoylated. FEBS Lett 309:402–404PubMedGoogle Scholar
  255. Prabhakar P, Cheng V, Michel T (2000) A chimeric transmembrane domain directs endothelial nitric oxide synthase palmitoylation and targeting to plasmalemmal caveolae. J Biol Chem 275:19416–19421PubMedGoogle Scholar
  256. Pritchard KA Jr, Ackerman AW, Gross ER, et al. (2001) Heat shock protein 90 mediates the balance of nitric oxide and superoxide anion from endothelial nitric oxide synthase. J Biol Chem 276:17621–17624PubMedGoogle Scholar
  257. Quintero M, Colombo S, Godfrey A, Moncada S (2006) Mitochondria as signaling organelles in the vascular endothelium. Proc Natl Acad Sci USA 103:5379–5384PubMedGoogle Scholar
  258. Radomski MW, Palmer RMJ, Moncada S (1987a) Comparative pharmacology of endothelium-derived relaxing factor, nitric oxide and prostacyclin in platelets. Br J Pharmacol 92:181–187PubMedGoogle Scholar
  259. Radomski MW, Palmer RMJ, Moncada S (1987b) The role of nitric oxide and cGMP in platelet adhesion to vascular endothelium. Biochem Biophys Res Commun 148:1482–1489PubMedGoogle Scholar
  260. Radomski MW, Palmer RMJ, Moncada S (1987c) The anti-aggregating properties of vascular endothelium: interactions between prostacyclin and nitric oxide. Br J Pharmacol 92:639–646PubMedGoogle Scholar
  261. Radomski MW, Palmer RMJ, Moncada S (1990a) Glucocorticoids inhibit the expression of an inducible, but not the constitutive, nitric oxide synthase in vascular endothelial cells. Proc Natl Acad Sci USA 87:10043–10047PubMedGoogle Scholar
  262. Radomski MW, Palmer RMJ, Moncada S (1990b) An L-arginine/nitric oxide pathway present in human platelets regulates aggregation. Proc Natl Acad Sci USA 87:5193–5197PubMedGoogle Scholar
  263. Radomski MW, Palmer RMJ, Moncada S (1990c) Characterization of the L-arginine:nitric oxide pathway in human platelets. Br J Pharmacol 101:325–328PubMedGoogle Scholar
  264. Rajagopalan S, Kurz S, Munzel T, et al. (1996) Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. J Clin Invest 97:1916–1923PubMedGoogle Scholar
  265. Raman CS, Li H, Martasek P, Kral V, et al. (1998) Crystal structure of constitutive endothelial nitric oxide synthase: a paradigm for pterin function involving a novel metal center. Cell 95:939–950PubMedGoogle Scholar
  266. Randiramboavonjy V, Schrader J, Busse R, et al. (2004) Insulin induces the release of vasodilator compounds from platelets by a nitric oxide-G-kinase-VAMP-3-dependent pathway. J Exp Med 199:347–356Google Scholar
  267. Rao GH, Krishnamurthi S, Raij L, et al. (1990) Influence of nitric oxide on agonist-mediated calcium mobilization in platelets. Biochem Med Metab Biol 43:271–275PubMedGoogle Scholar
  268. Razani B, Engelman JA, Wang XB, et al. (2001) Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. J Biol Chem 276:38121–38138PubMedGoogle Scholar
  269. Reddy KG, Nair RN, Sheehan HM, et al. (1994) Evidence that selective endothelial dysfunction may occur in the absence of angiographic or ultrasound atherosclerosis in patients with risk factors for atherosclerosis. J Am Coll Cardiol 23:833–843PubMedGoogle Scholar
  270. Rees DD, Palmer RMJ, Moncada S (1989) Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci USA 86:3375–3378PubMedGoogle Scholar
  271. Rees DD, Higgs EA, Moncada S (2000) Nitric oxide and the vessel wall. In: Colman RW, Hirsch J, Marder VJ, Clowes AW, George NJ (eds) Hemostasis and thrombosis. Lippincott Williams and Wilkins, Philadelphia, pp 673–682Google Scholar
  272. Robinson LJ, Michel T (1995) Mutagenesis of palmitoylation sites in endothelial nitric oxide synthase identifies a novel motif for dual acylation and subcellular targeting. Proc Natl Acad Sci USA 92:11776–11780PubMedGoogle Scholar
  273. Robinson LJ, Busconi L, Michel T (1995) Agonist-modulated palmitoylation of endothelial nitric oxide synthase. J Biol Chem 270:995–998PubMedGoogle Scholar
  274. Rosenkranz-Weiss P, Sessa WC, Milstien S, et al. (1994) Regulation of nitric oxide synthesis by proinflammatory cytokines in human umbilical vein endothelial cells. Elevations in tetrahydrobiopterin levels enhance endothelial nitric oxide synthase specific activity. J Clin Invest 93:2236–2243PubMedGoogle Scholar
  275. Russell KS, Haynes MP, Caulin-Glaser T, et al. (2000) Estrogen stimulates heat shock protein 90 binding to endothelial nitric oxide synthase in human vascular endothelial cells. Effects on calcium sensitivity and NO release. J Biol Chem 275:5026–5030PubMedGoogle Scholar
  276. Salerno JC, Harris DE, Irizarry K, et al. (1997) An autoinhibitory control element defines calcium-regulated isoforms of nitric oxide synthase. J Biol Chem 272:29769–29777PubMedGoogle Scholar
  277. Santolini J, Meade AL, Stuehr DJ (2001) Differences in three kinetic parameters underpin the unique catalytic profiles of nitric-oxide synthases I, II, and III. J Biol Chem 276:48887–48898PubMedGoogle Scholar
  278. Saura M, Zaragoza C, Cao W, et al. (2002) Smad2 mediates transforming growth factor-beta induction of endothelial nitric oxide synthase expression. Circ Res 91:806–813PubMedGoogle Scholar
  279. Sausbier M, Schubert R, Voigt V, et al. (2000) Mechanisms of NO/cGMP-dependent vasorelaxation. Circ Res 87:825–830PubMedGoogle Scholar
  280. Schachinger V, Britten MB, Zeiher AM (2000) Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation 101:1899–1906PubMedGoogle Scholar
  281. Schlossmann J, Hofmann F (2005) cGMP-dependent protein kinases in drug discovery. Drug Discov Today 10:627–634PubMedGoogle Scholar
  282. Schlossmann J, Ammendola A, Ashman K, et al. (2000) Regulation of intracellular calcium by a signalling complex of IRAG, IP3 receptor and cGMP kinase Iβ. Nature 404:197–201PubMedGoogle Scholar
  283. Schmidt H, Hofmann H, Schindler U, et al. (1996) No NO from NO synthase. Proc Natl Acad Sci USA 93:14492–14497PubMedGoogle Scholar
  284. Schneider MP, Erdmann J, Delles C, et al. (2000) Functional gene testing of the Glu298Asp polymorphism of the endothelial NO synthase. J Hypertens 18:1767–1773PubMedGoogle Scholar
  285. Schwarz UR, Walter U, Eigenthaler M (2001) Taming platelets with cyclic nucleotides. Biochem Pharmacol 62:1153–1161PubMedGoogle Scholar
  286. Schweizer M, Richter C (1994) Nitricoxide potently and reversibly deenergizes mitochondria at low oxygen tension. Biochem Biophys Res Commun 204:169–175PubMedGoogle Scholar
  287. Scotland RS, Chauhan S, Vallance PJ, et al. (2001) An endothelium-derived hyperpolarizing factor-like factor moderates myogenic constriction of mesenteric resistance arteries in the absence of endothelial nitric oxide synthase-derived nitric oxide. Hypertension 38:833–839PubMedGoogle Scholar
  288. Scotland RS, Morales-Ruiz M, Chen Y, et al. (2002) Functional reconstitution of endothelial nitric oxide synthase reveals the importance of serine 1179 in endothelium-dependent vasomotion. Circ Res 90:904–910PubMedGoogle Scholar
  289. Scotland RS, Madhani M, Chauhan S, et al. (2005) Investigation of vascular responses in endothelial nitric oxide synthase/cyclooxygenase-1 double-knockout mice. Key role for endothelium-derived hyperpolarizing factor in the regulation of blood pressure in vivo. Circulation 111:796–803PubMedGoogle Scholar
  290. Sessa WC (2004) eNOS at a glance. J Cell Sci 117:2427–2429PubMedGoogle Scholar
  291. Sessa WC, Harrison JK, Barber CM, et al. (1992) Molecular cloning and expression of a cDNA encoding endothelial cell nitric oxide synthase. J Biol Chem 267:15274–15276PubMedGoogle Scholar
  292. Shaul PA, Smart EJ, Robinson LJ, et al. (1996) Acylation targets endothelial nitric-oxide synthase to plasmalemmal caveolae. J Biol Chem 271:6518–6522PubMedGoogle Scholar
  293. Sherman PA, Laubach VE, Reep BR, et al. (1993) Purification and cDNA sequence of an inducible nitric oxide synthase from a human tumor cell line. Biochemistry 32:11600–11605PubMedGoogle Scholar
  294. Shesely EG, Maeda N, Kim HS, et al. (1996) Elevated blood pressures in mice lacking endothelial nitric oxide synthase. Proc Natl Acad Sci USA 93:13176–13181PubMedGoogle Scholar
  295. Shimasaki Y, Yasue H, Yoshimura M, et al. (1998) Association of the missense Glu298Asp variant of the endothelial nitric oxide synthase gene with myocardial infarction. J Am Coll Cardiol 31:1506–1510PubMedGoogle Scholar
  296. Siddhanta U, Wu C, Abu-Soud HM, et al. (1996) Hemeiron reduction and catalysis by a nitric oxide synthase heterodimer containing one reductase and two oxygenase domains. J Biol Chem 271:7309–7312PubMedGoogle Scholar
  297. Silacci P, Formentin K, Bouzourene K, et al. (2000) Unidirectional and oscillatory shear stress differentially modulate NOS III gene expression. Nitric Oxide 4:47–56PubMedGoogle Scholar
  298. Simon DI, Stamler JS, Loh E, et al. (1995) Effect of nitric oxide synthase inhibition on bleeding time in humans. J Cardiovasc Pharmacol 26:339–342PubMedGoogle Scholar
  299. Simoncini T, Hafezi-Moghadam A, Brazil DP, et al. (2000) Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase. Nature 407:538–541PubMedGoogle Scholar
  300. Slater TF (1972) Free radical mechanisms in tissue injury. Pion, LondonGoogle Scholar
  301. Solzbach U, Hornig B, Jeserich M, et al. (1997) Vitamin C improves endothelial dysfunction of epicardial coronary arteries in hypertensive patients. Circulation 96:1513–1519PubMedGoogle Scholar
  302. Sowa G, Liu J, Papapetropoulos A, et al. (1999) Trafficking of endothelial nitric oxide synthase in living cells. J Biol Chem 274:22524–22531PubMedGoogle Scholar
  303. Stagliano NE, Zhao W, Prado R, et al. (1997) The effect of nitric oxide synthase inhibition on acute platelet accumulation and hemodynamic depression in a rat model of thromboembolic stroke. J Cereb Blood Flow Metab 17:1182–1190PubMedGoogle Scholar
  304. Stamler JS, Hausladen A (1998) Oxidative modifications in nitrosative stress. Nat Struct Biol 5:247–249PubMedGoogle Scholar
  305. Stamler JS, Simon DI, Osborne JA, et al. (1992) S-nitrosylation of proteins with nitric oxide: synthesis and characterization of biologically active compounds. Proc Natl Acad Sci USA 89:444–448PubMedGoogle Scholar
  306. Stauss HM, Godecke A, Mrowka R, et al. (1999) Enhanced blood pressure variability in eNOS knock-out mice. Hypertension 33:1359–1363PubMedGoogle Scholar
  307. Stauss HM, Nafz B, Mrowka R, et al. (2000) Blood pressure control in eNOS knock-out mice: comparison with other species under NO blockade. Acta Physiol Scand 168:155–160PubMedGoogle Scholar
  308. Stemerman MB (1981) Vascular injury: platelets and smooth muscle cell response. Philos Trans R Soc Lond B Biol Sci 294:217–224PubMedGoogle Scholar
  309. Stroes E, Kastelein J, Cosentino F, et al. (1997) Tetrahydrobiopterin restores endothelial function in hypercholesterolemia. J Clin Invest 99:41–46PubMedGoogle Scholar
  310. Stuehr D, Pou S, Rosen GM (2001) Oxygen reduction by nitric oxide synthases. J Biol Chem 276:14533–14536PubMedGoogle Scholar
  311. Sun D, Huang A, Smith CJ, et al. (1999) Enhanced release of prostaglandins contributes to flow-induced arteriolar dilation in eNOS knockout mice. Circ Res 85:288–293PubMedGoogle Scholar
  312. Sun J, Liao JK (2002) Functional interaction of endothelial nitric oxide synthase with a voltage-dependent anion channel. Proc Natl Acad Sci USA 99:13108–13113PubMedGoogle Scholar
  313. Taddei S, Virdis A, Mattei P, et al. (1996) Defective L-arginine-nitric oxide pathway in offspring of essential hypertensive patients. Circulation 94:1298–1303PubMedGoogle Scholar
  314. Tai SC, Robb GB, Marsden PA (2004) Endothelial nitric oxide synthase: a new paradigm for gene regulation in the injured blood vessel. Arterioscler Thromb Vasc Biol 24:405–412PubMedGoogle Scholar
  315. Tiefenbacher CP, Chilian WM, Mitchell M, et al. (1996) Restoration of endothelium-dependent vasodilation after reperfusion injury by tetrahydrobiopterin. Circulation 94:1423–1429PubMedGoogle Scholar
  316. Ting HH, Timimi FK, Boles KS, et al. (1996) Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus. J Clin Invest 97:22–28PubMedGoogle Scholar
  317. Tracy RP (2002) Diabetes and atherothrombotic disease: linked through inflammation? Semin Vasc Med 2:67–73PubMedGoogle Scholar
  318. Trovati M, Massucco P, Mattiello L, et al. (1996) The insulin-induced increase of guanosine-3′,5′-cyclic monophosphate in human platelets is mediated by nitric oxide. Diabetes 45:768–770PubMedGoogle Scholar
  319. Turrens JF (2003) Mitochondrial formation of reactive oxygen species. J Physiol 552:335–344PubMedGoogle Scholar
  320. Uematsu M, Ohara Y, Navas JP, et al. (1995) Regulation of endothelial cell nitric oxide synthase mRNA expression by shear stress. Am J Physiol 269:C1371–C1378PubMedGoogle Scholar
  321. Uwabo J, Soma M, Nakayama T, et al. (1998) Association of a variable number of tandem repeats in the endothelial constitutive nitric oxide synthase gene with essential hypertension in Japanese. Am J Hypertens 11:125–128PubMedGoogle Scholar
  322. Vallance P, Moncada S (1993) Role of endogenous nitric oxide in septic shock. New Horiz 1:77–86PubMedGoogle Scholar
  323. Vallance P, Collier J, Moncada S (1989) Nitric oxide synthesized from L-arginine mediates endothelium-dependent dilatation in human veins in vivo. Cardiovasc Res 23:1053–1057PubMedGoogle Scholar
  324. Vallance P, Leone A, Calver A, et al. (1992) Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 339:572–575PubMedGoogle Scholar
  325. van der Zee R, Murohara T, Luo Z, et al. (1997) Vascular endothelial growth factor/vascular permeability factor augments nitric oxide release from quiescent rabbit and human vascular endothelium. Circulation 95:1030–1037PubMedGoogle Scholar
  326. van Geel PP, Pinto YM, Buikema H, et al. (1998) Is the A1166C polymorphism of the angiotensin II type 1 receptor involved in cardiovascular disease? Eur Heart J 19:G13–G17PubMedGoogle Scholar
  327. Varenne O, Pislaru S, Gillijns H, et al. (1998) Local adenovirus-mediated transfer of human endothelial nitric oxide synthase reduces luminal narrowing after coronary angioplasty in pigs. Circulation 98:919–926PubMedGoogle Scholar
  328. Vasquez-Vivar J, Kalyanaraman B, Martasek P, et al. (1998) Superoxide generation by endothelial nitric oxide synthase: the influence of cofactors. Proc Natl Acad Sci USA 95:9220–9225PubMedGoogle Scholar
  329. Venema RC, Venema VJ, Ju H, et al. (2003) Novel complexes of guanylate cyclase with heat shock protein 90 and nitric oxide synthase. Am J Physiol 285:H669–H678Google Scholar
  330. Viner RI, Williams TD, Schoneich C (1999) Peroxynitrite modification of protein thiols: oxidation, nitrosylation, and S-glutathiolation of functionally important cysteine residue(s) in the sarcoplasmic reticulum Ca-ATPase. Biochemistry 38:12408–12415PubMedGoogle Scholar
  331. Virdis A, Schiffrin EL (2003) Vascular inflammation: a role in vascular disease in hypertension? Curr Opin Nephrol Hypertens 12:181–187PubMedGoogle Scholar
  332. Vodovotz Y, Chesler L, Chong H, et al. (1999) Regulation of transforming growth factor β1 by nitric oxide. Cancer Res 59:2142–2149PubMedGoogle Scholar
  333. von der Leyen HE, Dzau VJ (2001) Therapeutic potential of nitric oxide synthase gene manipulation. Circulation 103:2760–2765PubMedGoogle Scholar
  334. Vouldoukis I, Riveros-Moreno V, Dugas B, et al. (1995) The killing of Leishmania major by human macrophages is mediated by nitric oxide induced after ligation of the Fc epsilon RII/CD23 surface antigen. Proc Natl Acad Sci USA 92:7804–7808PubMedGoogle Scholar
  335. Wagner AH, Kohler T, Ruckschloss U, et al. (2000a) Improvement of nitric oxide-dependent vasodilatation by HMG-CoA reductase inhibitors through attenuation of endothelial superoxide anion formation. Arterioscler Thromb Vasc Biol 20:61–69PubMedGoogle Scholar
  336. Wagner C, Godecke A, Ford M, et al. (2000b) Regulation of renin gene expression in kidneys of eNOS-and nNOS-deficient mice. Pflugers Arch 439:567–572PubMedGoogle Scholar
  337. Walker G, Pfeilshifter J, Kunz D (1997) Mechanisms of suppression of inducible nitric oxide synthase (iNOS) expression in interferon (IFN)-γ-stimulated RAW 264.7 cells by dexamethasone. Evidence for glucocorticoid-induced degradation of iNOS protein by calpain as a key step in post-transcriptional regulation. J Biol Chem 272:16679–16687PubMedGoogle Scholar
  338. Wallerath T, Gath I, Aulitzky WE, et al. (1997) Identification of the NO synthase isoforms expressed in human neutrophil granulocytes, megakaryocytes and platelets. Thromb Haemost 77:163–167PubMedGoogle Scholar
  339. Wang X, Wang J, Trudinger B (2003) Gene expression of nitric oxide synthase by human umbilical vein endothelial cells: the effect of fetal plasma from pregnancy with umbilical placental vascular disease. Br J Obstet Gynaecol 110:53–58Google Scholar
  340. Wang XL, Wang J (2000) Endothelial nitric oxide synthase gene sequence variations and vascular disease. Mol Genet Metab 70:241–251PubMedGoogle Scholar
  341. Wattanapitayakul SK, Mihm MJ, Young AP, et al. (2001) Therapeutic implications of human endothelial nitric oxide synthase gene polymorphism. Trends Pharmacol Sci 22:361–368PubMedGoogle Scholar
  342. Wedgwood S, Mitchell CJ, Fineman JR, et al. (2003) Developmental differences in the shear stress-induced expression of endothelial NO synthase: changing role of AP-1. Am J Physiol Lung Cell Mol Physiol 284:L650–L662PubMedGoogle Scholar
  343. Wei CC, Wang ZQ, Meade AL, et al. (2002) Why do nitric oxide synthases use tetrahydrobiopterin? J Inorg Biochem 91:6618–6624Google Scholar
  344. Weiner CP, Lizasoain I, Baylis SA, et al. (1994) Induction of calcium-dependent nitric oxide synthases by sex hormones. Proc Natl Acad Sci USA 91:5212–5216PubMedGoogle Scholar
  345. Werner ER, Gorren AC, Heller R, et al. (2003) Tetrahydrobiopterin and nitric oxide: mechanistic and pharmacological aspects. Exp Biol Med 228:1291–1302Google Scholar
  346. White KA, Marletta MA (1992) Nitric oxide synthase is a cytochrome P-450 type hemoprotein. Biochemistry 31:6627–6631PubMedGoogle Scholar
  347. Whittle BJR (1997) Nitric oxide—a mediator of inflammation or mucosal defence. Eur J Gastroenterol Hepatol 9:1026–1032PubMedGoogle Scholar
  348. Wilcox JN, Subramanian RR, Sundell CL, et al. (1997) Expression of multiple isoforms of nitric oxide synthase in normal and atherosclerotic vessels. Arterioscler Thromb Vasc Biol 17:2479–2488PubMedGoogle Scholar
  349. Xie QW, Cho HJ, Calaycay J, et al. (1992) Cloning and characterization of inducible nitric oxide synthase from mouse macrophages. Science 256:225–228PubMedGoogle Scholar
  350. Xu HL, Galea E, Santizo RA, et al. (2001) The key role of caveolin-1 in estrogen-mediated regulation of endothelial nitric oxide synthase function in cerebral arterioles in vivo. J Cereb Blood Flow Metab 21:907–913PubMedGoogle Scholar
  351. Xu KY, Huso DL, Dawson TM, et al. (1999) Nitric oxide synthase in cardiac sarcoplasmic reticulum. Proc Natl Acad Sci USA 96:657–662PubMedGoogle Scholar
  352. Xu L, Eu JP, Meissner G, et al. (1998) Activation of the cardiac calcium release channel (ryanodine receptor) by poly-S-nitrosylation. Science 279:234–237PubMedGoogle Scholar
  353. Yang Y, Loscalzo J (2005) S-nitrosoprotein formation and localization in endothelial cells. Proc Natl Acad Sci USA 102:117–122PubMedGoogle Scholar
  354. Yeh DC, Duncan JA, Yamashita S, et al. (1999) Depalmitoylation of endothelial nitric oxide synthase by acyl-protein thioesterase 1 is potentiated by Ca2+-calmodulin. J Biol Chem 274:33148–33154PubMedGoogle Scholar
  355. Zabel U, Kleinschnitz C, Oh P, et al. (2002) Calcium-dependent membrane association sensitizes soluble guanylyl cyclase to nitric oxide. Nat Cell Biol 4:307–311PubMedGoogle Scholar
  356. Zembowicz A, Tang JL, Wu KK (1995) Transcriptional induction of endothelial nitric oxide synthase type III by lysophosphatidylcholine. J Biol Chem 270:17006–17010PubMedGoogle Scholar
  357. Zhang R, Min W, Sessa WC (1995) Functional analysis of the human endothelial nitric oxide synthase promoter. Sp1 and GATA factors are necessary for basal transcription in endothelial cells. J Biol Chem 270:15320–15326PubMedGoogle Scholar
  358. Zhao G, Bernstein RD, Hintze TH (1999) Nitric oxide and oxygen utilization: exercise, heart failure and diabetes. Coron Artery Dis 10:315–320PubMedGoogle Scholar
  359. Zhao YY, Liu Y, Stan RV, et al. (2002) Defects in caveolin-1 cause dilated cardiomyopathy and pulmonary hypertension in knockout mice. Proc Natl Acad Sci USA 99:11375–11380PubMedGoogle Scholar
  360. Ziche M, Morbidelli L (2000) Nitric oxide and angiogenesis. J Neurooncol 50:139–148PubMedGoogle Scholar
  361. Ziche M, Morbidelli L, Masini E, et al. (1994) Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P. J Clin Invest 94:2036–2044PubMedGoogle Scholar
  362. Ziche M, Morbidelli L, Choudhuri R, et al. (1997) Nitric oxide synthase lies downstream from vascular endothelial growth factor-induced but not basic fibroblast growth factor-induced angiogenesis. J Clin Invest 99:2625–2634PubMedGoogle Scholar
  363. Ziegler T, Silacci P, Harrison VJ, et al. (1998) Nitric oxide synthase expression in endothelial cells exposed to mechanical forces. Hypertension 32:351–355PubMedGoogle Scholar
  364. Zimmermann K, Optiz N, Dedio J, et al. (2002) NOSTRIN: a protein modulating nitric oxide release and subcellular distribution of endothelial nitric oxide synthase. Proc Natl Acad Sci USA 99:17167–17172PubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  1. 1.The Wolfson Institute for Biomedical ResearchUniversity College LondonLondonUK

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