Vasoconstrictor prostanoids

  • Michel FélétouEmail author
  • Yu Huang
  • Paul M. Vanhoutte
Invited Review


In cardiovascular diseases and during aging, endothelial dysfunction is due in part to the release of endothelium-derived contracting factors that counteract the vasodilator effect of the nitric oxide. Endothelium-dependent contractions involve the activation of endothelial cyclooxygenases and the release of various prostanoids, which activate thromboxane prostanoid (TP) receptors of the underlying vascular smooth muscle. The stimulation of TP receptors elicits not only the contraction and the proliferation of vascular smooth muscle cells but also diverse physiological/pathophysiological reactions, including platelet aggregation and activation of endothelial inflammatory responses. TP receptor antagonists curtail endothelial dysfunction in diseases such as hypertension and diabetes, are potent antithrombotic agents, and prevent vascular inflammation.


Hypertension Diabetes Aging Endothelium-dependent contraction TP receptors EDCF 


  1. 1.
    Alvarez de Sotomayor M, Mingorance C, Andriantsitohaina R (2007) Fenofibrate improves age-related endothelial dysfunction in rat resistance arteries. Atherosclerosis 193:112–120PubMedCrossRefGoogle Scholar
  2. 2.
    Alvarez Y, Briones AM, Balfagón G, Alonso MJ, Salaices M (2005) Hypertension increases the participation of vasoconstrictor prostanoids from cyclooxygenase-2 in phenylephrine responses. J Hypertens 23:767–777PubMedCrossRefGoogle Scholar
  3. 3.
    Arikawa E, Cheung C, Sekirov I, Battell ML, Yuen VG, McNeill JH (2006) Effects of endothelin receptor blockade on hypervasoreactivity in streptozotocin-diabetic rats: vessel-specific involvement of thromboxane A2. Can J Physiol Pharmacol 84:823–833PubMedCrossRefGoogle Scholar
  4. 4.
    Auch-Schwelk W, Katusic ZS, Vanhoutte PM (1989) Contractions to oxygen-derived free radicals are augmented in aorta of the spontaneously hypertensive rat. Hypertension 13:859–864PubMedGoogle Scholar
  5. 5.
    Auch-Schwelk W, Katusic ZS, Vanhoutte PM (1990) Thromboxane A2 receptor antagonists inhibit endothelium-dependent contractions. Hypertension 15:699–703PubMedGoogle Scholar
  6. 6.
    Belhassen L, Pelle G, Dubois-Rande J, Adnot S (2003) Improved endothelial function by the thromboxane a2 receptor antagonist s 18886 in patients with coronary artery disease treated with aspirin. J Am Coll Cardiol 41:1198–1204PubMedCrossRefGoogle Scholar
  7. 7.
    Blanco-Rivero J, Cachofeiro V, Lahera V, Aras-Lopez R, Márquez-Rodas I, Salaices M, Xavier FE, Ferrer M, Balfagón G (2005) Participation of prostacyclin in endothelial dysfunction induced by aldosterone in normotensive and hypertensive rats. Hypertension 46:107–112PubMedCrossRefGoogle Scholar
  8. 8.
    Camacho M, Lopez-Belmonte J, Vila L (1998) Rate of vasoconstrictor prostanoids released by endothelial cells depends on cyclooxygenase-2 expression and prostaglandin I synthase activity. Circ Res 83:353–365PubMedGoogle Scholar
  9. 9.
    Cayatte AJ, Du Y, Oliver-Krasinski J, Lavielle G, Verbeuren TJ, Cohen RA (2000) The thromboxane receptor antagonist S18886 but not aspirin inhibits atherogenesis in apo E-deficient mice: evidence that eicosanoids other than thromboxane contribute to atherosclerosis. Arterioscler Thromb Vasc Biol 20:1724–1728PubMedGoogle Scholar
  10. 10.
    Chenevard R, Hürlimann D, Béchir M, Enseleit F, Spieker L, Hermann M, Riesen W, Gay S, Gay RE, Neidhart M, Michel B, Lüscher TF, Noll G, Ruschitzka F (2003) Selective COX-2 inhibition improves endothelial function in coronary artery disease. Circulation 107:405–409PubMedCrossRefGoogle Scholar
  11. 11.
    Cohen RA (2002) Does EDCF contribute to diabetic endothelial cell dysfunction? Dialog Cardiovasc Med 7:225–231Google Scholar
  12. 12.
    Davidge ST (2001) Prostaglandin H synthase and vascular function. Circ Res 89:650–660PubMedCrossRefGoogle Scholar
  13. 13.
    De Mey JG, Vanhoutte PM (1982) Heterogeneous behavior of the canine arterial and venous wall. Importance of the endothelium. Circ Res 51:439–447PubMedGoogle Scholar
  14. 14.
    De Vriese AS, Verbeuren TJ, Van de Voorde J, Lameire NH, Vanhoutte PM (2000) Endothelial dysfunction in diabetes. Br J Pharmacol 130:963–974PubMedCrossRefGoogle Scholar
  15. 15.
    De Witt DL, Day JS, Sonnenburg WK, Smith WL (1983) Concentrations of prostaglandin endoperoxide synthase and prostaglandin I2 synthase in the endothelium and smooth muscle of bovine aorta. J Clin Invest 72:1882–1888CrossRefGoogle Scholar
  16. 16.
    De Witt DL, Smith WL (1988) Primary structure of prostaglandin G/H synthase from sheep vesicular gland determined from the complementary DNA sequence. Proc Natl Acad Sci U S A 85:1412–1416CrossRefGoogle Scholar
  17. 17.
    Félétou M, Vanhoutte PM (2006) Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture). Am J Physiol Heart Circ Physiol 291:H985–H1002PubMedCrossRefGoogle Scholar
  18. 18.
    Félétou M, Vanhoutte PM, Verbeuren TJ (2010) The TP-receptor: the common villain. J Cardiovasc Pharmacol (in press)Google Scholar
  19. 19.
    Flavahan NA (2007) Balancing prostanoid activity in the human vascular system. Trends Pharmacol Sci 28:106–110PubMedCrossRefGoogle Scholar
  20. 20.
    Fonlupt P, Croset M, Lagarde M (1991) 12-HETE inhibits the binding of PGH2/TXA2 receptor ligands in human platelets. Thromb Res 63:239–248PubMedCrossRefGoogle Scholar
  21. 21.
    Funk CD, FitzGerald GA (2007) COX-2 inhibitors and cardiovascular risk. J Cardiovasc Pharmacol 50:470–479PubMedCrossRefGoogle Scholar
  22. 22.
    Garcia-Cohen EC, Marin J, Diez-Picazo LD, Baena AB, Salaices M, Rodriguez-Martinez MA (2000) Oxidative stress induced by tert-butyl hydroperoxide causes vasoconstriction in the aorta from hypertensive and aged rats: role of cyclooxygenase-2 isoform. J Pharmacol Exp Ther 293:75–81PubMedGoogle Scholar
  23. 23.
    Ge T, Hughes H, Junquero DC, Wu KK, Vanhoutte PM, Boulanger CM (1995) Endothelium dependent contractions are associated with both augmented expression of prostaglandin H synthase-1 and hypersensitivity to prostaglandin H2 in the SHR aorta. Circ Res 76:1003–1010PubMedGoogle Scholar
  24. 24.
    Gendron ME, Thorin E (2007) A change in the redox environment and thromboxane A2 production precede endothelial dysfunction in mice. Am J Physiol Heart Circ Physiol 293:H2508–H2515PubMedCrossRefGoogle Scholar
  25. 25.
    Gluais P, Lonchampt M, Morrow JD, Vanhoutte PM, Félétou M (2005) Acetylcholine-induced endothelium-dependent contractions in the SHR aorta: the Janus face of prostacyclin. Br J Pharmacol 146:834–845PubMedCrossRefGoogle Scholar
  26. 26.
    Gluais P, Paysant J, Badier-Commander C, Verbeuren T, Vanhoutte PM, Félétou M (2006) In SHR aorta, calcium ionophore A-23187 releases prostacyclin and thromboxane A2 as endothelium-derived contracting factors. Am J Physiol Heart Circ Physiol 291:H2255–H2564PubMedCrossRefGoogle Scholar
  27. 27.
    Gluais P, Vanhoutte PM, Félétou M (2007) Mechanisms underlying ATP-induced endothelium-dependent contractions in the SHR aorta. Eur J Pharmacol 556:107–114PubMedCrossRefGoogle Scholar
  28. 28.
    Gomez E, Schwendemann C, Roger S, Simonet S, Paysant J, Courchay C, Verbeuren TJ, Félétou M (2008) Aging and prostacyclin responses in aorta and platelets from WKY and SHR rats. Am J Physiol Heart Circ Physiol 295:H2198–H2211PubMedCrossRefGoogle Scholar
  29. 29.
    Graham DA, Rush JW (2009) Cyclooxygenase and thromboxane/prostaglandin receptor contribute to aortic endothelium-dependent dysfunction in aging female spontaneously hypertensive rats. J Appl Physiol 107:1059–1067PubMedCrossRefGoogle Scholar
  30. 30.
    Gryglewski RJ, Palmer RM, Moncada S (1986) Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature 320:454–456PubMedCrossRefGoogle Scholar
  31. 31.
    Harlan JM, Callahan KS (1984) Role of hydrogen peroxide in the neutrophil-mediated release of prostacyclin from cultured endothelial cells. J Clin Invest 74:442–448PubMedCrossRefGoogle Scholar
  32. 32.
    Heymes C, Habib A, Yang D, Mathieu E, Marotte F, Samuel JL, Boulanger CM (2000) Cyclo-oxygenase-1 and –2 contribution to endothelial dysfunction in ageing. Br J Pharmacol 131:804–810PubMedCrossRefGoogle Scholar
  33. 33.
    Hla T, Neilson K (1992) Human cyclooxygenase-2 cDNA. Proc Natl Acad Sci U S A 89:7384–7388PubMedCrossRefGoogle Scholar
  34. 34.
    Iwama Y, Kato T, Muramatsu M, Asano H, Shimizu K, Toki Y, Miyazaki Y, Okumura K, Hashimoto H, Ito T, Satake T (1992) Correlation with blood pressure of the acetylcholine-induced endothelium-derived contracting factor in the rat aorta. Hypertension 19:326–332PubMedGoogle Scholar
  35. 35.
    Kato T, Iwama Y, Okumura K, Hashimoto H, Ito T, Satake T (1990) Prostaglandin H2 may be the endothelium-derived contracting factor released by acetylcholine in the aorta of the rat. Hypertension 15:475–481PubMedGoogle Scholar
  36. 36.
    Katugampola SD, Davenport AP (2001) Thromboxane receptor density is increased in human cardiovascular disease with evidence for inhibition at therapeutic concentrations by the AT(1) receptor antagonist losartan. Br J Pharmacol 134:1385–1392PubMedCrossRefGoogle Scholar
  37. 37.
    Katusic Z, Shepherd JT, Vanhoutte PM (1987) Endothelium-dependent contraction to stretch in canine basilar arteries. Am J Physiol 21:H671–H673Google Scholar
  38. 38.
    Katusic ZS, Shepherd JT, Vanhoutte PM (1988) Endothelium-dependent contractions to calcium ionophore A23187, arachidonic acid and acetylcholine in canine basilar arteries. Stroke 19:476–479PubMedGoogle Scholar
  39. 39.
    Katusic ZS, Vanhoutte PM (1989) Superoxide anion is an endothelium-derived contracting factor. Am J Physiol 257:H33–H37PubMedGoogle Scholar
  40. 40.
    Kauser K, Rubanyi GM (1995) Gender difference in endothelial dysfunction in the aorta of spontaneously hypertensive rats. Hypertension 25:517–523PubMedGoogle Scholar
  41. 41.
    Kawka DW, Ouellet M, Hétu PO, Singer II, Riendeau D (2007) Double-label expression studies of prostacyclin synthase, thromboxane synthase and COX isoforms in normal aortic endothelium. Biochim Biophys Acta 1771:45–54PubMedGoogle Scholar
  42. 42.
    Kiriyama M, Ushikubi F, Kobayashi T, Hirata M, Sugimoto Y, Narumiya S (1997) Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells. Br J Pharmacol 122:217–224PubMedCrossRefGoogle Scholar
  43. 43.
    Koga T, Takata Y, Kobayashi K, Takeshita S, Yamashita Y, Fujishima M (1988) Ageing suppresses endothelium-dependent relaxation and generates contraction mediated by the muscarinic receptors in vascular smooth muscle of normotensive Wistar Kyoto and spontaneously hypertensive rats. J Hypertens 6:S243–S245Google Scholar
  44. 44.
    Koga T, Takata Y, Kobayashi K, Takishita S, Yamashita Y, Fujishima M (1989) Age and hypertension promote endothelium-dependent contractions to acetylcholine in the aorta of the rat. Hypertension 14:542–548PubMedGoogle Scholar
  45. 45.
    Liu CQ, Leung FP, Wong SL, Wong WT, Lau CW, Lu L, Yao X, Yao T, Huang Y (2009) Thromboxane prostanoid receptor activation impairs endothelial nitric oxide-dependent vasorelaxations: the role of Rho kinase. Biochem Pharmacol 78:374–381PubMedCrossRefGoogle Scholar
  46. 46.
    Lüscher TF, Vanhoutte PM (1986) Endothelium-dependent contractions to acetylcholine in the aorta of the spontaneously hypertensive rat. Hypertension 8:344–348PubMedGoogle Scholar
  47. 47.
    Lüscher TF, Cooke JP, Houston DS, Neves RJ, Vanhoutte PM (1987) Endothelium-dependent relaxations in human arteries. Mayo Clin Proc 62:601–606PubMedGoogle Scholar
  48. 48.
    Matsumoto T, Kakami M, Noguchi E, Kobayashi T, Kamata K (2007) Imbalance between endothelium-derived relaxing and contracting factors in mesenteric arteries from aged OLETF rats, a model of Type 2 diabetes. Am J Physiol Heart Circ Physiol 293:H1480–H1490PubMedCrossRefGoogle Scholar
  49. 49.
    Matz RL, de Sotomayor MA, Schott C, Stoclet JC, Andriantsitohaina R (2000) Vascular bed heterogeneity in age-related endothelial dysfunction with respect to NO and eicosanoids. Br J Pharmacol 131:303–311PubMedCrossRefGoogle Scholar
  50. 50.
    Mazzone T, Chait A, Plutzky J (2008) Cardiovascular disease risk in type 2 diabetes mellitus: insights from mechanistic studies. Lancet 371:1800–1809PubMedCrossRefGoogle Scholar
  51. 51.
    McAdam BF, Catella-Lawson F, Mardini IA, Kapoor S, Lawson JA, FitzGerald GA (1999) Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. Proc Natl Acad Sci U S A 96:272–277PubMedCrossRefGoogle Scholar
  52. 52.
    Meeking D, Browne D, Allard S, Munday J, Chowienczyk P, Shaw KM, Cummings MH (2000) Effects of cyclo-oxygenase inhibition on vasodilatory response to acetylcholine in patients with type 1 diabetes and nondiabetic. Diabetes Care 23:1–4CrossRefGoogle Scholar
  53. 53.
    Merlie JP, Fagan D, Mudd J, Needleman P (1988) Isolation and characterization of the complementary DNA for sheep seminal prostaglandins endoperoxide synthase (cyclooxygenase). J Biol Chem 263:3550–3553PubMedGoogle Scholar
  54. 54.
    Miller VM, Vanhoutte PM (1985) Endothelium-dependent contractions to arachidonic acid are mediated by products of cyclo-oxygenase in canine veins. Am J Physiol 248:H432–H437PubMedGoogle Scholar
  55. 55.
    Moncada S, Gryglewski RJ, Bunting S, Vane JR (1976) An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 263:663–665PubMedCrossRefGoogle Scholar
  56. 56.
    Moncada S, Herman AG, Higgs EA, Vane JR (1977) Differential formation of prostacyclin (PGX or PGI2) by layers of the arterial wall. An explanation for the anti-thrombotic properties of vascular endothelium. Thromb Res 11:323–344PubMedCrossRefGoogle Scholar
  57. 57.
    Moncada S, Vane JR (1979) Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane A2 and prostacyclin. Pharmacol Rev 30:293–331Google Scholar
  58. 58.
    Morikawa K, Matoba T, Kubota H, Hatanaka M, Fujiki T, Takahashi S, Takeshita A, Shimokawa H (2005) Influence of diabetes mellitus, hypercholesterolemia, and their combination on EDHF-mediated responses in mice. J Cardiovasc Pharmacol 45:485–490PubMedCrossRefGoogle Scholar
  59. 59.
    Morrow JD, Hill KE, Burk RF, Nannour TM, Badr KF, Roberts LJ II (1990) A series of prostaglandins F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical catalysed mechanism. Proc Natl Acad Sci U S A 87:9383–9387PubMedCrossRefGoogle Scholar
  60. 60.
    Nacci C, Tarquinio M, De Benedictis L, Mauro A, Zigrino A, Carratù MR, Quon MJ, Montagnani M (2009) Endothelial dysfunction in mice with streptozotocin-induced type 1 diabetes is opposed by compensatory overexpression of cyclooxygenase-2 in the vasculature. Endocrinology 150:849–861PubMedCrossRefGoogle Scholar
  61. 61.
    Nakahata N (2008) Thromboxane A2: physiology/pathophysiology, cellular signal transduction and pharmacology. Pharmacol Ther 118:18–35PubMedCrossRefGoogle Scholar
  62. 62.
    Numaguchi Y, Harada M, Osanai H, Hayashi K, Toki Y, Okamura K, Ito T, Hayakawa T (1999) Altered gene expression of prostacyclin synthase and prostacyclin receptor in the thoracic aorta of spontaneously hypertensive rats. Cardiovasc Res 41:682–688PubMedCrossRefGoogle Scholar
  63. 63.
    O’Banion MK, Winn VD, Young DA (1992) cDNA cloning and functional activity of a glucocorticoid-regulated inflammatory cyclooxygenase. Proc Natl Acad Sci U S A 89:4888–4892PubMedCrossRefGoogle Scholar
  64. 64.
    Onodera M, Morita I, Mano Y, Murota S (2000) Differential effects of nitric oxide on the activity of prostaglandin endoperoxide H synthase-1 and -2 in vascular endothelial cells. Prostaglandins Leukot Essent Fatty Acids 62:161–167PubMedCrossRefGoogle Scholar
  65. 65.
    Radomski MW, Palmer RMJ, Moncada S (1987) Comparative pharmacology of endothelium-derived relaxing factor, nitric oxide and prostacyclin in platelets. Br J Pharmacol 92:181–187PubMedGoogle Scholar
  66. 66.
    Radomski MW, Palmer RMJ, Moncada S (1987) The anti-aggregating properties of vascular endothelium: interactions between prostacyclin and nitric oxide. Br J Pharmacol 92:639–646PubMedGoogle Scholar
  67. 67.
    Rapoport RM, Williams SP (1996) Role of prostaglandins in acetylcholine-induced contraction of aorta from spontaneously hypertensive and Wistar-Kyoto rats. Hypertension 28:64–75PubMedGoogle Scholar
  68. 68.
    Rovati GE, Sala, A, Capra V, Dahlen SE, Folco G. (2010) Dual COXIB/TP antagonists: a possible new twist in NASID pharmacology and cardiovascular risk. Trends Pharmacol Sci 31:102–107Google Scholar
  69. 69.
    Rubanyi GM, Vanhoutte PM (1986) Superoxide anions and hyperoxia inactivate endothelium-derived relaxing factor. Am J Physiol 250:H222–H227Google Scholar
  70. 70.
    Shi Y, Feletou M, Ku DD, Man RYK, Vanhoutte PM (2007) The calcium ionophore A23187 induces endothelium-dependent contractions in femoral arteries from rats with streptozotocin-induced diabetes. Br J Pharmacol 150:624–632PubMedCrossRefGoogle Scholar
  71. 71.
    Shi Y, Man RY, Vanhoutte PM (2008) Two isoforms of cyclooxygenase contribute to augmented endothelium-dependent contractions in femoral arteries of 1-year-old rats. Acta Pharmacol Sin 29:185–192PubMedCrossRefGoogle Scholar
  72. 72.
    Shimizu K, Muramatsu M, Kakegawa Y, Asano H, Toki Y, Miyazaki Y, Okumura K, Hashimoto H, Ito T (1993) Role of prostaglandin H2 as an endothelium-derived contracting factor in diabetic state. Diabetes 42:1246–1252PubMedCrossRefGoogle Scholar
  73. 73.
    Smith WL, Marnett LJ (1991) Prostaglandin endoperoxide synthase: structure and catalysis. Biochem Biophys Acta 1083:1–17PubMedGoogle Scholar
  74. 74.
    Suzuki YJ, Ford GD (1992) Superoxide stimulates IP3-induced Ca2+ release from vascular smooth muscle sarcoplasmic reticulum. Am J Physiol 262:H114–H116PubMedGoogle Scholar
  75. 75.
    Taddei S, Vanhoutte PM (1993) Role of endothelium in endothelin-evoked contractions in the rat aorta. Hypertension 21:9–15PubMedGoogle Scholar
  76. 76.
    Taddei S, Virdis A, Ghiadoni L, Magagna A, Salvetti A (1997) Cyclooxygenase inhibition restores nitric oxide activity in essential hypertension. Hypertension 29:274–279PubMedGoogle Scholar
  77. 77.
    Taddei S, Virdis A, Mattei P, Ghiadoni L, Fasolo CB, Sudano I, Salvetti A (1997) Hypertension causes premature aging of endothelial function in humans. Hypertension 29:736–743PubMedGoogle Scholar
  78. 78.
    Taddei S, Virdis A, Mattei P, Ghiadoni L, Gennari A, Fasolo CB, Sudano I, Salvetti A (1995) Aging and endothelial function in normotensive subjects and patients with essential hypertension. Circulation 91:1981–1987PubMedGoogle Scholar
  79. 79.
    Tang EH, Ku DD, Tipoe GL, Félétou M, Man RY, Vanhoutte PM (2005) Endothelium-dependent contractions occur in the aorta of wild-type and COX2-/- knockout but not COX1-/- knockout mice. J Cardiovasc Pharmacol 46:761–765PubMedCrossRefGoogle Scholar
  80. 80.
    Tang EH, Leung FP, Huang Y, Félétou M, So KF, Man RY, Vanhoutte PM (2007) Calcium and reactive oxygen species increase in endothelial cells in response to releasers of endothelium-derived contracting factor. Br J Pharmacol 151:15–23PubMedCrossRefGoogle Scholar
  81. 81.
    Tang EH, Vanhoutte PM (2008) Gene expression changes of prostanoid synthases in endothelial cells and prostanoid receptors in vascular smooth muscle cells caused by aging and hypertension. Physiol Genomics 32:409–418PubMedGoogle Scholar
  82. 82.
    Tesfamariam B, Brown ML, Cohen RA (1995) 15-Hydroxyeicosatetraenoic acid and diabetic endothelial dysfunction in rabbit aorta. J Cardiovasc Pharmacol 25:748–755PubMedCrossRefGoogle Scholar
  83. 83.
    Topper JN, Cai J, Falb D, Gimbrone MA Jr (1996) Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress. Proc Natl Acad Sci U S A 93:10417–10422PubMedCrossRefGoogle Scholar
  84. 84.
    Tsuboi K, Sugimoto Y, Ichikawa A (2002) Prostanoid receptor subtypes. Prostaglandins Other Lipid Mediat 68–69:535–556PubMedCrossRefGoogle Scholar
  85. 85.
    Valentin F, Field MC, Tippins JR (2004) The mechanism of oxidative stress stabilization of the thromboxane receptor in COS-7 cells. J Biol Chem 279:8316–8324PubMedCrossRefGoogle Scholar
  86. 86.
    Van Diest MJ, Verbeuren TJ, Herman AG (1991) 15-lipoxygenase metabolites of arachidonic acid evoke contractions and relaxations in isolated canine arteries: role of thromboxane receptors, endothelial cells and cyclooxygenase. J Pharmacol Exp Ther 256:194–203PubMedGoogle Scholar
  87. 87.
    Vane J, Bakhle YS, Botting RM (1998) Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol 38:97–120PubMedCrossRefGoogle Scholar
  88. 88.
    Vanhoutte PM, Félétou M, Taddei S (2005) Endothelium-dependent contractions in hypertension. Br J Pharmacol 144:449–458PubMedCrossRefGoogle Scholar
  89. 89.
    Verbeuren TJ (2006) Terutroban and endothelial TP receptors in atherogenesis. Med Sci (Paris) 22:437–443Google Scholar
  90. 90.
    Virdis A, Colucci R, Versari D, Ghisu N, Fornai M, Antonioli L, Duranti E, Daghini E, Giannarelli C, Blandizzi C, Taddei S, Del Tacca M (2009) Atorvastatin prevents endothelial dysfunction in mesenteric arteries from spontaneously hypertensive rats: role of cyclooxygenase 2-derived contracting prostanoids. Hypertension 53:1008–1016PubMedCrossRefGoogle Scholar
  91. 91.
    Watkins MT, Patton GM, Soler HM, Albadawi H, Humphries DE, Evans JE, Kadowaki K (1999) Synthesis of 8-epi-prostaglandinF2α by human endothelial cells: role of prostaglandin H2 synthase. Biochem J 344:747–775PubMedCrossRefGoogle Scholar
  92. 92.
    Widlansky ME, Price DT, Gokce N, Eberhardt RT, Duffy SJ, Holbrook M, Maxwell C, Palmisano J, Keaney JF Jr, Morrow JD, Vita JA (2003) Short- and long-term COX-2 inhibition reverses endothelial dysfunction in patients with hypertension. Hypertension 42:310–315PubMedCrossRefGoogle Scholar
  93. 93.
    Wilson SJ, Cavanagh CC, Lesher AM, Frey AJ, Russell SE, Smyth EM (2009) Activation-dependent stabilization of the human thromboxane receptor: role of reactive oxygen species. J Lipid Res 50:1047–1056PubMedCrossRefGoogle Scholar
  94. 94.
    Wise H, Jones RL (1996) Focus on prostacyclin and its novel mimetics. Trends Pharmacol Sci 17:17–21PubMedCrossRefGoogle Scholar
  95. 95.
    Wong MS, Man RY, Vanhoutte PM. (2010) Calcium-independent phospholipase A2 plays a key role in the endothelium-dependent contractions to acetylcholine in the aorta of SHR. Am J Physiol Heart Circ Physiol (in press)Google Scholar
  96. 96.
    Wong SL, Leung FP, Lau CW, Vanhoutte P, Huang Y (2008) Endothelium-dependent contractions in hamster aorta: the essential role of COX-2 and prostaglandin-2α. Basic Clin Pharmacol Toxicol 102(suppl 1):15–15Google Scholar
  97. 97.
    Wong SL, Leung FP, Lau CW, Au CL, Yung LM, Yao X, Chen ZY, Vanhoutte PM, Gollasch M, Huang Y (2009) Cyclooxygenase-2-derived prostaglandin F2alpha mediates endothelium-dependent contractions in the aortae of hamsters with increased impact during aging. Circ Res 104:228–235PubMedCrossRefGoogle Scholar
  98. 98.
    Wotherspoon F, Browne DL, Meeking DR, Allard SE, Munday LJ, Shaw KM, Cummings MH (2005) The contribution of nitric oxide and vasodilatory prostanoids to bradykinin-mediated vasodilation in Type 1 diabetes. Diabet Med 22:697–702PubMedCrossRefGoogle Scholar
  99. 99.
    Xavier FE, Aras-López R, Arroyo-Villa I, Campo LD, Salaices M, Rossoni LV, Ferrer M, Balfagón G (2008) Aldosterone induces endothelial dysfunction in resistance arteries from normotensive and hypertensive rats by increasing thromboxane A2 and prostacyclin. Br J Pharmacol 154:1225–1235PubMedCrossRefGoogle Scholar
  100. 100.
    Yang D, Félétou M, Boulanger CM, Wu HF, Levens N, Zhang JN, Vanhoutte PM (2002) Oxygen-derived free radicals mediate endothelium-dependent contractions to acetylcholine in aortas from spontaneously hypertensive rats. Br J Pharmacol 136:104–110PubMedCrossRefGoogle Scholar
  101. 101.
    Yang D, Félétou M, Levens N, Zhang JN, Vanhoutte PM (2003) A diffusible substance(s) mediates endothelium-dependent contractions in the aorta of SHR. Hypertension 41:143–148PubMedCrossRefGoogle Scholar
  102. 102.
    Yang D, Levens N, Zhang JN, Vanhoutte PM, Félétou M (2003) Specific potentiation of endothelium-dependent contractions in SHR by tetrahydrobiopterin. Hypertension 41:136–142PubMedCrossRefGoogle Scholar
  103. 103.
    Yang D, Gluais P, Zhang JN, Vanhoutte PM, Félétou M (2004) Endothelium-dependent contractions to acetylcholine, ATP and the calcium ionophore A 23187 in aortas from spontaneously hypertensive and normotensive rats. Fundam Clin Pharmacol 18:321–326PubMedCrossRefGoogle Scholar
  104. 104.
    Yokohama C, Takai T, Tanabe T (1988) Primary structure of sheep prostaglandin endoperoxide synthase deduced from cDNA sequence. FEBS Lett 231:347–351CrossRefGoogle Scholar
  105. 105.
    Zerrouk A, Auguet M, Chabrier PE (1998) Augmented endothelium-dependent contraction to angiotensin II in the SHR aorta: role of an inducible cyclooxygenase metabolite. J Cardiovasc Pharmacol 31:525–533PubMedCrossRefGoogle Scholar
  106. 106.
    Zhou Y, Mitra S, Varadharaj S, Parinandi N, Zweier JL, Flavahan NA (2006) Increased expression of cyclooxygenase-2 mediates enhanced contraction to endothelin ETA receptor stimulation in endothelial nitric oxide synthase knockout mice. Circ Res 98:1439–1445PubMedCrossRefGoogle Scholar
  107. 107.
    Zou MH, Shi C, Cohen RA (2002) High glucose via peroxynitrite causes tyrosine nitration and inactivation of prostacyclin synthase that is associated with thromboxane/prostaglandin H(2) receptor-mediated apoptosis and adhesion molecule expression in cultured human aortic endothelial cells. Diabetes 51:198–203PubMedCrossRefGoogle Scholar

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© Springer-Verlag 2010

Authors and Affiliations

  • Michel Félétou
    • 1
    Email author
  • Yu Huang
    • 2
  • Paul M. Vanhoutte
    • 3
    • 4
  1. 1.Institut Recherches ServierSuresnesFrance
  2. 2.Institute of Vascular Medicine, Li Ka Shing Institute of Health Sciences, and School of Biomedical SciencesChinese University of Hong KongHong KongChina
  3. 3.Department Pharmacology and Pharmacy, Li Ka Shing Faculty MedicineUniversity of Hong KongHong KongChina
  4. 4.Department BIN Fusion TechnologyChonbuk National UniversityJeonjuKorea

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