Heart Failure Reviews

, Volume 8, Issue 1, pp 107–115

The Nitric Oxide-Endothelin-1 Connection



Nitric oxide (NO) and endothelin-1 (ET-1) are endothelium-derived mediators that play important roles in vascular homeostasis. This review is focused on the role and reciprocal interactions between NO and ET-1 in health and diseases associated with endothelium dysfunction. We will also discuss the clinical significance of NO donors and drugs that antagonize ET receptors.

nitric oxide endothelin vascular tone cardiovascular system receptor antagonist heart failure 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Cooke M, John P, Dzau M, Victor J. Nitric oxide synthase: Role in the genesis of vascular disease. Annu Rev Medicine 1997;48:489-509.Google Scholar
  2. 2.
    Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987;327:524-526.Google Scholar
  3. 3.
    Moncada S, Radomski MW, Palmer RM. Endotheliumderived relaxing factor. Identification as nitric oxide and role in the control of vascular tone and platelet function. Biochem Pharmacol 1988;37:2495-2501.Google Scholar
  4. 4.
    Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980;288:373-376.Google Scholar
  5. 5.
    Marletta MA. Nitric oxide synthase: Aspects concerning structure and catalysis. Cell 1994;78:927-930.Google Scholar
  6. 6.
    Knowles RG, Palacios M, Palmer RM, Moncada S. Formation of nitric oxide from L-arginine in the central nervous system: A transduction mechanism for stimulation of the soluble guanylate cyclase. Proceedings of the National Academy of Sciences of the United States of America 1989;86:5159-5162.Google Scholar
  7. 7.
    Bredt DS, Snyder SH. Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proceedings of the National Academy of Sciences of the United States of America 1990;87:682-685.Google Scholar
  8. 8.
    Moncada S, Higgs EA. Endogenous nitric oxide: Physiology, pathology and clinical relevance. Eur J Clin Invest 1991;21:361-374.Google Scholar
  9. 9.
    Forstermann U, Schmidt HH, Pollock JS, Sheng H, Mitchell JA, Warner TD, Nakane M, Murad F. Isoforms of nitric oxide synthase. Characterization and purification from different cell types. Biochem Pharmacol 1991;42:1849-1857.Google Scholar
  10. 10.
    Moncada S, Palmer RM, Higgs EA. Nitric oxide: Physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991;43:109-142.Google Scholar
  11. 11.
    Pollock JS, Forstermann U, Mitchell JA, Warner TD, Schmidt HH, Nakane M, Murad F. Purification and characterization of particulate endothelium-derived relaxing factor synthase from cultured and native bovine aortic endothelial cells. Proc Natl Acad Sci USA 1991;88:10480-10484.Google Scholar
  12. 12.
    Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA 1987;84:9265-9269.Google Scholar
  13. 13.
    Palmer RM, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 1988;333:664-666.Google Scholar
  14. 14.
    Marletta MA, Yoon PS, Iyengar R, Leaf CD, Wishnok JS. Macrophage oxidation of L-arginine to nitrite and nitrate: Nitric oxide is an intermediate. Biochem 1988;27:8706-8711.Google Scholar
  15. 15.
    Szabo C, Thiemermann C. Regulation of the expression of the inducible isoform of nitric oxide synthase. Adv Pharmacol 1995;34:113-153.Google Scholar
  16. 16.
    Radomski MW, Salas E. Nitric oxide-biological mediator, modulator and factor of injury: Its role in the pathogenesis of atherosclerosis. Atherosclerosis 1995;118 (suppl):S69-S80.Google Scholar
  17. 17.
    Schulz R, Smith JA, Lewis MJ, Moncada S. Nitric oxide synthase in cultured endocardial cells of the pig. Br J Pharmacol 1991;104:21-24.Google Scholar
  18. 18.
    Balligand JL, Kobzik L, Han X, Kaye DM, Belhassen L, O Hara DS, Kelly RA, Smith TW, Michel T. Nitric oxidedependent parasympathetic signaling is due to activation of constitutive endothelial (type III) nitric oxide synthase in cardiac myocytes. J Biol Chem 1995;270:14582-14586.Google Scholar
  19. 19.
    Schulz R, Nava E, Moncada S. Induction and potential biological relevance of a Ca(2+)-independent nitric oxide synthase in the myocardium. Br J Pharmacol 1992;105:575-580.Google Scholar
  20. 20.
    Balligand JL, Ungureanu Longrois D, Simmons WW, Pimental D, Malinski TA, Kapturczak M, Taha Z, Lowenstein CJ, Davidoff AJ, Kelly RA. Cytokine-inducible nitric oxide synthase (iNOS) expression in cardiac myocytes. Characterization and regulation of iNOS expression and detection of iNOS activity in single cardiac myocytes in vitro. J Biol Chem 1994;269:27580-27588.Google Scholar
  21. 21.
    Cooke JP, Rossitch E, Andon NA, Loscalzo J, Dzau VJ. Flow activates an endothelial potassium channel to release an endogenous nitrovasodilator. J Clin Invest 1991;88:1663-1671.Google Scholar
  22. 22.
    Radomski MW, Palmer RM, Moncada S. Comparative pharmacology of endothelium-derived relaxing factor, nitric oxide and prostacyclin in platelets. Br J Pharmacol 1987;92:181-187.Google Scholar
  23. 23.
    Radomski MW, Palmer RM, Moncada S. Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. Lancet 1987;2:1057-1058.Google Scholar
  24. 24.
    Radomski MW, Palmer RM, Moncada S. The role of nitric oxide and cGMP in platelet adhesion to vascular endothelium. Biochem Biophys Res Commun 1987;148:1482-1489.Google Scholar
  25. 25.
    Radomski MW, Palmer RM, Moncada S. The antiaggregating properties of vascular endothelium: Interactions between prostacyclin and nitric oxide. Br J Pharmacol 1987;92:639-646.Google Scholar
  26. 26.
    Taddei S, Virdis A, Ghiadoni L, Salvetti A. Vascular effects of endothelin-1 in essential hypertension: Relationship with cyclooxygenase-derived endothelium-dependent contracting factors and nitric oxide. J Cardiovasc Pharmacol 2000;35(4):S37-S40.Google Scholar
  27. 27.
    Kojda G, Kottenberg K. Regulation of basal myocardial function by NO. Cardiovasc Res 1999;41:514-523.Google Scholar
  28. 28.
    Hickey KA, Rubanyi G, Paul RJ, Highsmith RF. Characterization of a coronary vasoconstrictor produced by cultured endothelial cells. Am J Physiol 1985;248:C550-C556.Google Scholar
  29. 29.
    O'Brien RF, Robbins RJ, McMurtry IF. Endothelial cells in culture produce a vasoconstrictor substance. J Cell Physiol 1987;132:263-270.Google Scholar
  30. 30.
    Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988;332:411-415.Google Scholar
  31. 31.
    Kedzierski RM, Yanagisawa M. Endothelin system: The double-edged sword in health and disease. Annu Rev Pharmacol Toxicol 2001;41:851-876.Google Scholar
  32. 32.
    Inoue A, Yanagisawa M, Kimura S, Kasuya Y, Miyauchi T, Goto K, Masaki T. The human endothelin family: Three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Natl Acad Sci USA 1989;86:2863-2867.Google Scholar
  33. 33.
    Denault JB, Claing A, DOrleans-Juste P, Sawamura T, Kido T, Masaki T, Leduc R. Processing of proendothelin-1 by human furin convertase. FEBS Lett 1995;362:276-280.Google Scholar
  34. 34.
    Kimura S, Kasuya Y, Sawamura T, Shinimi O, Sugita Y, Yanagisawa M, Goto K, Masaki T. Conversion of big endothelin-1 to 21-residue endothelin-1 is essential for expression of full vasoconstrictor activity: Structure-activity relationships of big endothelin-1. J Cardiovasc Pharmacol 1989;13 (suppl. 5):S5-S7Google Scholar
  35. 35.
    Matsumura Y, Hisaki K, Takaoka M, Morimoto S. Phosphoramidon, a metalloproteinase inhibitor, suppresses the hypertensive effect of big endothelin-1. Eur J Pharmacol 1990;185:103-106.Google Scholar
  36. 36.
    Shimada K, Takahashi M, Tanzawa K. Cloning and functional expression of endothelin-converting enzyme from rat endothelial cells. J Biol Chem 1994;269:18275-18278.Google Scholar
  37. 37.
    Xu D, Emoto N, Giaid A, Slaughter C, Kaw S, deWit D, Yanagisawa M. ECE-1: A membrane-bound metalloprotease that catalyzes the proteolytic activation of big endothelin-1. Cell 1994;78:473-485.Google Scholar
  38. 38.
    Emoto N, Yanagisawa M. Endothelin-converting enzyme-2 is a membrane-bound, phosphoramidon-sensitive metalloprotease with acidic pH optimum. J Biol Chem 1995;270:15262-15268.Google Scholar
  39. 39.
    Korth P, Bohle RM, Corvol P, Pinet F. Cellular distribution of endothelin-converting enzyme-1 in human tissues. J Histochem Cytochem 1999;47:447-462.Google Scholar
  40. 40.
    Schweizer A, Valdenaire O, Nelbock P, Deuschle U, Dumas-Milne-Edwards JB, Stumpf JG, Loffler BM. Human endothelin-converting enzyme (ECE-1): Three isoforms with distinct subcellular localizations. Biochem J 1997;328 (pt. 3):871-877.Google Scholar
  41. 41.
    Valdenaire O, Lepailleur-Enouf D, Egidy G, Thouard A, Barret A, Vranckx R, Tougard C, Michel J-B. A fourth isoform of endothelin-converting enzyme (ECE-1) is generated from an additional promoter: Molecular cloning and characterization. Eur J Biochem 1999;264:341-349.Google Scholar
  42. 42.
    Fernandez-Patron C, Radomski MW, Davidge ST. Vascular matrix metalloproteinase-2 cleaves big endothelin-1 yielding a novel vasoconstrictor. Circ Res 1999;85:906-911.Google Scholar
  43. 43.
    Fernandez-Patron C, Zouki C, Whittal R, Chan JS, Davidge ST, Filep JG. Matrix metalloproteinases regulate neutrophil-endothelial cell adhesion through generation of endothelin-1 [1-32]. FASEB J 2001;15:2230-2240.Google Scholar
  44. 44.
    Inoue A, Yanagisawa M, Takuwa Y, Mitsui Y, Kobayashi M, Masaki T. The human preproendothelin-1 gene. Complete nucleotide sequence and regulation of expression. J Biol Chem 1989;264:14954-14959.Google Scholar
  45. 45.
    Lee ME, Bloch KD, C lifford JA, Quertermous T. Functional analysis of the endothelin-1 gene promoter. Evidence for an endothelial cell-specific cis-acting sequence. The Journal of Biological Chemistry 1990;265:10446-10450.Google Scholar
  46. 46.
    Kawana M, Lee ME, Quertermous EE, Quertermous T. Cooperative interaction of GATA-2 and AP1 regulates transcription of the endothelin-1 gene. Mol Cell Biol 1995;15:4225-4231.Google Scholar
  47. 47.
    Arai H, Hori S, Aramori I, Ohkubo H, Nakanishi S. Cloning and expression of a cDNA encoding an endothelin receptor. Nature 1990;348:730-732.Google Scholar
  48. 48.
    Sakurai T, Yanagisawa M, Takuwa Y, Miyazaki H, Kimura S, Goto K, Masaki T. Cloning of a cDNA encoding a nonisopeptide-selective subtype of the endothelin receptor. Nature 1990;348:732-735.Google Scholar
  49. 49.
    Takuwa Y, Kasuya Y, Takuwa N, Kudo M, Yanagisawa M, Goto K, Masaki T, Yamashita K. Endothelin receptor is coupled to phospholipase C via a pertussis toxininsensitive guanine nucleotide-binding regulatory protein in vascular smooth muscle cells. J Clin Invest 1990;85:653-658.Google Scholar
  50. 50.
    Griendling KK, Tsuda T, Alexander RW. Endothelin stimulates diacylglycerol accumulation and activates protein kinase C in cultured vascular smooth muscle cells. J Biol Chem 1989;264:8237-8240.Google Scholar
  51. 51.
    Simonson MS, Dunn MJ. Cellular signaling by peptides of the endothelin gene family. FASEB J 1990;4:2989-3000.Google Scholar
  52. 52.
    Haynes WG, Webb DJ. Endothelin as a regulator of cardiovascular function in health and disease. J Hypertens 1998;16:1081-1098.Google Scholar
  53. 53.
    Haynes WG, Webb DJ. Contribution of endogenous generation of endothelin-1 to basal vascular tone. Lancet 1994;344:852-854.Google Scholar
  54. 54.
    Haynes WG, Ferro CJ, O Kane KP, Somerville D, Lomax CC, Webb DJ. Systemic endothelin receptor blockade decreases peripheral vascular resistance and blood pressure in humans. Circulation 1996;93:1860-1870.Google Scholar
  55. 55.
    Woods M, Mitchell JA, Wood EG, Barker S, Walcot NR, Rees GM, Warner TD. Endothelin-1 is induced by cytokines in human vascular smooth muscle cells: Evidence for intracellular endothelin-converting enzyme. Molecular Pharmacology 1999;55:902-909.Google Scholar
  56. 56.
    Wagner OF, Christ G, Wojta J, Vierhapper H, Parzer S, Nowotny PJ, Schneider B, Waldhausl W, Binder BR. Polar secretion of endothelin-1 by cultured endothelial cells. J Biol Chem 1992;267:16066-16068.Google Scholar
  57. 57.
    Wright CE, Fozard JR. Regional vasodilation is a prominent feature of the haemodynamic response to endothelin in anaesthetized, spontaneously hypertensive rats. Eur J Pharmacol 1988;155:201-203.Google Scholar
  58. 58.
    de Nucci G, Thomas R, D Orleans-Juste P, Antunes E, Walder C, Warner TD, Vane JR. Pressor effects of circulating endothelin are limited by its removal in the pulmonary circulation and by the release of prostacyclin and endothelium-derived relaxing factor. Proc Natl Acad Sci USA 1988;85:9797-9800.Google Scholar
  59. 59.
    Haynes WG, Strachan FE, Webb DJ. Endothelin ETA and ETB receptors cause vasoconstriction of human resistance and capacitance vessels in vivo. Circulation 1995;92:357-363.Google Scholar
  60. 60.
    Miyauchi T, Masaki T. Pathophysiology of endothelin in the cardiovascular system. Annu Rev Physiol 1999;61:391-415.Google Scholar
  61. 61.
    Cardillo C, Kilcoyne CM, Cannon RO, Panza JA. Interactions between nitric oxide and endothelin in the regulation of vascular tone of human resistance vessels in vivo. Hypertension 2000;35:1237-1241.Google Scholar
  62. 62.
    Carville C, Adnot S, Sediame S, Benacerraf S, Castaigne A, Calvo F, de Cremou P, Dubois-Rande JL. Relation between impairment in nitric oxide pathway and clinical status in patients with congestive heart failure. J Cardiovasc Pharmacol 1998;32:562-570.Google Scholar
  63. 63.
    Treasure CB, Vita JA, Cox DA, Fish RD, Gordon JB, Mudge GH, Colucci WS, Sutton MG, Selwyn AP, Alexander RW. Endothelium-dependent dilation of the coronary microvasculature is impaired in dilated cardiomyopathy. Circulation 1990;81:772-779.Google Scholar
  64. 64.
    Drexler H, Hayoz D, Munzel T, Just H, Zelis R, Brunner HR. Endothelial function in congestive heart failure. Am Heart J 1993;126:761-764.Google Scholar
  65. 65.
    Arimura K, Egashira K, Nakamura R, Ide T, Tsutsui H, Shimokawa H, Takeshita A. Increased inactivation of nitric oxide is involved in coronary endothelial dysfunction in heart failure. Am J Physiol Heart Circ Physiol 2001;280:H68-H75.Google Scholar
  66. 66.
    Yoshizumi M, Perrella MA, Burnett JC, Lee ME. Tumor necrosis factor downregulates an endothelial nitric oxide synthase mRNA by shortening its half-life. Circ Res 1993;73:205-209.Google Scholar
  67. 67.
    de Belder AJ, Radomski MW, Why HJ, Richardson PJ, Bucknall CA, Salas E, Martin JF, Moncada S. Nitric oxide synthase activities in human myocardium. Lancet 1993;341:84-85.Google Scholar
  68. 68.
    Miyauchi T, Yanagisawa M, Tomizawa T, Sugishita Y, Suzuki N, Fujino M, Ajisaka R, Goto K, Masaki T. Increased plasma concentrations of endothelin-1 and big endothelin-1 in acute myocardial infarction. Lancet 1989;2:53-54.Google Scholar
  69. 69.
    McMurray JJ, Ray SG, Abdullah I, Dargie HJ, Morton JJ. Plasma endothelin in chronic heart failure. Circulation 1992;85:1374-1379.Google Scholar
  70. 70.
    Rodeheffer RJ, Lerman A, Heublein DM, Burnett JC. Increased plasma concentrations of endothelin in congestive heart failure in humans. Mayo Clin Proc 1992;67:719- 724.Google Scholar
  71. 71.
    Wei C, Lerman A, Rodeheffer R, McGregor C, Brandt R, W right S, Heublein D, Kao P, Edwards W, Burnett J, Jr. Endothelin in human congestive heart failure. Circulation 1994;89:1580-1586.Google Scholar
  72. 72.
    Pacher R, S tanek B, Hulsmann M, Koller Strametz J, Berger R, Schuller M, Hartter E, Ogris E, Frey B, Heinz G, Maurer G. Prognostic impact of big endothelin-1 plasma concentrations compared with invasive hemodynamic evaluation in severe heart failure. J AmColl Cardiol 1996;27:633-641.Google Scholar
  73. 73.
    Serneri GGN, Cecioni I, Vanni S, Paniccia R, Bandinelli B, Vetere A, Janming X, Bertolozzi I, Boddi M, Lisi GF, Sani G, Modesti PA. Selective upregulation of cardiac endothelin system in patients with ischemic but not idiopathic dilated cardiomyopathy: Endothelin-1 system in the human failing heart. Circ Res 2000;86:377-385.Google Scholar
  74. 74.
    Kahler J, Mendel S, Weckmuller J, Orzechowski HD, Mittmann C, Koster R, Paul M, Meinertz T, Munzel T. Oxidative stress increases synthesis of big endothelin-1 by activation of the endothelin-1 promoter. J Mol Cell Cardiol 2000;32:1429-1437.Google Scholar
  75. 75.
    Suzuki S, Kajikuri J, Suzuki A, Itoh T. Effects of endothelin-1 on endothelial cells in the porcine coronary artery. Circ Res 1991;69:1361-1368.Google Scholar
  76. 76.
    Verhaar MC, Strachan FE, Newby DE, Cruden NL, Koomans HA, Rabelink TJ, Webb DJ. Endothelin-A receptor antagonist-mediated vasodilatation is attenuated by inhibition of nitric oxide synthesis and by endothelin-B receptor blockade. Circulation 1998;97:752-756.Google Scholar
  77. 77.
    Lerman A, Sandok EK, Hildebrand FL, Burnett JC. Inhibition of endothelium-derived relaxing factor enhances endothelin-mediated vasoconstriction. Circulation 1992;85:1894-1898.Google Scholar
  78. 78.
    Ahlborg G, Lundberg JM. Nitric oxide-endothelin-1 interaction in humans. J Appl Physiol 1997;82:1593-1600.Google Scholar
  79. 79.
    Banting JD, Friberg P, Adams MA. Acute hypertension after nitric oxide synthase inhibition is mediated primarily by increased endothelin vasoconstriction. J Hypertens 1996;14:975-981.Google Scholar
  80. 80.
    Boulanger C, Luscher TF. Release of endothelin from the porcine aorta. Inhibition by endothelium-derived nitric oxide. J Clin Invest 1990;85:587-590.Google Scholar
  81. 81.
    Warner TD, Schmidt HH, Murad F. Interactions of endothelins and EDRF in bovine native endothelial cells: Selective effects of endothelin-3. Am J Physiol 1992;262:H1600-H1605.Google Scholar
  82. 82.
    Gray GA, Webb DJ. The endothelin system and its potential as a therapeutic target in cardiovascular disease. Pharmacol Ther 1996;72:109-148.Google Scholar
  83. 83.
    Redmond EM, Cahill PA, Hodges R, Zhang S, Sitzmann JV. Regulation of endothelin receptors by nitric oxide in cultured rat vascular smooth muscle cells. J Cell Physiol 1996;166:469-479.Google Scholar
  84. 84.
    Ahn K, Sisneros AM, Herman SB, Pan SM, Hupe D, Lee C, Nikam S, Cheng XM, Doherty AM, Schroeder RL, Haleen SJ, Kaw S, Emoto N, Yanagisawa M. Novel selective quinazoline inhibitors of endothelin converting enzyme-1. Biochem Biophys Res Commun 1998;243:184-190.Google Scholar
  85. 85.
    Martin P, Tzanidis A, Stein Oakley A, Krum H. Effect of a highly selective endothelin-converting enzyme inhibitor on cardiac remodeling in rats after myocardial infarction. J Cardiovasc Pharmacol 2000;36:S367-S370.Google Scholar
  86. 86.
    Trapani AJ, Beil ME, Bruseo CW, De Lombaert S, Jeng AY. Pharmacological properties of CGS 35066, a potent and selective endothelin-converting enzyme inhibitor, in conscious rats. J Cardiovasc Pharmacol 2000;36:S40- S43.Google Scholar
  87. 87.
    Sutsch G, Kiowski W, Yan XW, Hunziker P, Christen S, Strobel W, Kim JH, Rickenbacher P, Bertel O. Short-term oral endothelin-receptor antagonist therapy in conventionally treated patients with symptomatic severe chronic heart failure. Circulation 1998;98:2262-2268.Google Scholar
  88. 88.
    Packer M, Caspi A, Charlon V, La Roche H, Cohen-Solal A, Kiowski W. Multicenter, double-blind, placebo-controlled study of long-term endothelin blockade with bosentan in chronic heart failure-results of the REACH-1 trial. Circulation 1998;98 (suppl.):1-3.Google Scholar
  89. 89.
    Ono K, Matsumori A. Endothelin antagonism with bosentan: Current status and future perspectives. Cardiovasc Drug Rev 2002;20:1-18.Google Scholar
  90. 90.
    Schalcher C, Cotter G, Reisin L, Bertel O, Kobrin I, Guyene TT, Kiowski W. The dual endothelin receptor antagonist tezosentan acutely improves hemodynamic parameters in patients with advanced heart failure. Am Heart J 2001;142:340-349.Google Scholar
  91. 91.
    Torre Amione G, Durand JB, Nagueh S, Vooletich MT, Kobrin I, Pratt C. A pilot safety trial of prolonged (48 h) infusion of the dual endothelin-receptor antagonist tezosentan in patients with advanced heart failure. Chest 2001;120:460-466.Google Scholar
  92. 92.
    Cowburn PJ, Cleland JG, McArthur JD, MacLean MR, McMurray JJ, Dargie HJ. Short-term haemodynamic effects of BQ-123, a selective endothelin ET(A)-receptor antagonist, in chronic heart failure. Lancet 1998;352:201-202.Google Scholar
  93. 93.
    Gonon AT, Gourine AV, Pernow J. Cardioprotection from ischemia and reperfusion injury by an endothelin A-receptor antagonist in relation to nitric oxide production. J Cardiovasc Pharmacol 2000;36:405-412.Google Scholar
  94. 94.
    Givertz MM, Colucci WS, LeJemtel TH, Gottlieb SS, Hare JM, Slawsky MT, Leier CV, Loh E, Nicklas JM, Lewis BE. Acute endothelin A receptor blockade causes selective pulmonary vasodilation in patients with chronic heart failure. Circulation 2000;101:2922-2927.Google Scholar
  95. 95.
    Elkayam U, Karaalp IS, Wani OR, Tummala P, Akhter MW. The role of organic nitrates in the treatment of heart failure. Prog Cardiovasc Dis 1999;41:255-264.Google Scholar
  96. 96.
    Wiley KE, Davenport AP. Novel nitric oxide donors reverse endothelin-1-mediated constriction in human blood vessels. J Cardiovasc Pharmacol 2000;36:S151-S152.Google Scholar
  97. 97.
    Alonso D, Radomski MW. Nitric oxide, platelet function, myocardial infarction and reperfusion therapies. Heart Fail Rev 2002.Google Scholar
  98. 98.
    Hunt SA, Baker DW, Chin MH, Cinquegrani MP, Feldmanmd AM, Francis GS, Ganiats TG, Goldstein S, Gregoratos G, Jessup ML, Noble RJ, Packer M, Silver MA, Stevenson LW, Gibbons RJ, Antman EM, Alpert JS, Faxon DP, Fuster V, Jacobs AK, Hiratzka LF, Russell RO, Smith SC, and ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: Executive summary. A report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure): Developed in Collaboration with the International Society for Heart and Lung Transplantation; endorsed by the Heart Failure Society of America. Circulation 2001;104:2996-3007.Google Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  1. 1.Department of Integrative Biology and PharmacologyUniversity of Texas-HoustonUSA

Personalised recommendations