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Endothelial dysfunction: a strategic target in the treatment of hypertension?

  • Cardiovascular Physiology
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

Endothelial dysfunction is a common feature of hypertension, and it results from the imbalanced release of endothelium-derived relaxing factors (EDRFs; in particular, nitric oxide) and endothelium-derived contracting factors (EDCFs; angiotensin II, endothelins, uridine adenosine tetraphosphate, and cyclooxygenase-derived EDCFs). Thus, drugs that increase EDRFs (using direct nitric oxide releasing compounds, tetrahydrobiopterin, or l-arginine supplementation) or decrease EDCF release or actions (using cyclooxygenase inhibitor or thromboxane A2/prostanoid receptor antagonists) would prevent the dysfunction. Many conventional antihypertensive drugs, including angiotensin-converting enzyme inhibitors, calcium channel blockers, and third-generation β-blockers, possess the ability to reverse endothelial dysfunction. Their use is attractive, as they can address arterial blood pressure and vascular tone simultaneously. The severity of endothelial dysfunction correlates with the development of coronary artery disease and predicts future cardiovascular events. Thus, endothelial dysfunction needs to be considered as a strategic target in the treatment of hypertension.

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References

  1. Félétou M, Vanhoutte PM (2006) Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture). Am J Physiol Heart Circ Physiol 291:H985–H1002

    Article  PubMed  CAS  Google Scholar 

  2. Susic D (1997) Hypertension, aging, and atherosclerosis. The endothelial interface. Med Clin North Am 81:1231–1240

    Article  CAS  PubMed  Google Scholar 

  3. Flavahan NA, Vanhoutte PM (1990) G-proteins and endothelial responses. Blood Vessels 27:218–229

    CAS  PubMed  Google Scholar 

  4. Shibano T, Codina J, Birnbaumer L, Vanhoutte PM (1994) Pertussis toxin-sensitive G proteins in regenerated endothelial cells of porcine coronary artery. Am J Physiol 267:H979–H981

    CAS  PubMed  Google Scholar 

  5. Tang EH, Vanhoutte PM (2009) Prostanoids and reactive oxygen species: team players in endothelium-dependent contractions. Pharmacol Ther 122:140–149

    Article  CAS  PubMed  Google Scholar 

  6. Vanhoutte PM, Shimokawa H, Tang EH, Feletou M (2009) Endothelial dysfunction and vascular disease. Acta Physiol (Oxf) 196:193–222

    Article  CAS  Google Scholar 

  7. Michel FS, Man GS, Man RY, Vanhoutte PM (2008) Hypertension and the absence of EDHF-mediated responses favour endothelium-dependent contractions in renal arteries of the rat. Br J Pharmacol 155:217–226

    Article  CAS  PubMed  Google Scholar 

  8. Sekiguchi F, Nakahira T, Kawata K, Sunano S (2002) Responses to endothelium-derived factors and their interaction in mesenteric arteries from Wistar Kyoto and stroke-prone spontaneously hypertensive rats. Clin Exp Pharmacol Physiol 29:1066–1074

    Article  CAS  PubMed  Google Scholar 

  9. 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 18:321–326

    Article  CAS  PubMed  Google Scholar 

  10. Lee J, Choi KC, Yeum CH, Kim W, Yoo K, Park JW, Yoon PJ (1995) Impairment of endothelium-dependent vasorelaxation in chronic two-kidney, one-clip hypertensive rats. Nephrol Dial Transplant 10:619–623

    CAS  PubMed  Google Scholar 

  11. Stankevicius E, Martinez AC, Mulvany MJ, Simonsen U (2002) Blunted acetylcholine relaxation and nitric oxide release in arteries from renal hypertensive rats. J Hypertens 20:1571–1579

    Article  CAS  PubMed  Google Scholar 

  12. Cordellini S (1999) Endothelial dysfunction in DOCA-salt hypertension: possible involvement of prostaglandin endoperoxides. Gen Pharmacol 32:315–320

    Article  CAS  PubMed  Google Scholar 

  13. Zhou MS, Kosaka H, Tian RX, Abe Y, Chen QH, Yoneyama H, Yamamoto A, Zhang L (2001) l-Arginine improves endothelial function in renal artery of hypertensive Dahl rats. J Hypertens 19:421–429

    Article  CAS  PubMed  Google Scholar 

  14. Zhou MS, Nishida Y, Chen QH, Kosaka H (1999) Endothelium-derived contracting factor in carotid artery of hypertensive Dahl rats. Hypertension 34:39–43

    CAS  PubMed  Google Scholar 

  15. Linder L, Kiowski W, Bühler FR, Lüscher TF (1990) Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo. Blunted response in essential hypertension. Circulation 81:1762–1767

    CAS  PubMed  Google Scholar 

  16. Panza JA, Quyyumi AA, Brush JE Jr, Epstein SE (1990) Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med 323:22–27

    Article  CAS  PubMed  Google Scholar 

  17. Panza JA, Casino PR, Kilcoyne CM, Quyyumi AA (1993) Role of endothelium-derived nitric oxide in the abnormal endothelium-dependent vascular relaxation of patients with essential hypertension. Circulation 87:1468–1474

    CAS  PubMed  Google Scholar 

  18. Félétou M, Vanhoutte PM (2006) Endothelium-derived hyperpolarizing factor: where are we now? Arterioscler Thromb Vasc Biol 26:1215–1225

    Article  PubMed  CAS  Google Scholar 

  19. Higashi Y, Sasaki S, Nakagawa K, Fukuda Y, Matsuura H, Oshima T, Chayama K (2002) Tetrahydrobiopterin enhances forearm vascular response to acetylcholine in both normotensive and hypertensive individuals. Am J Hypertens 15:326–332

    Article  CAS  PubMed  Google Scholar 

  20. Sessa WC (2005) Regulation of endothelial derived nitric oxide in health and disease. Mem Inst Oswaldo Cruz 100:15–18

    Article  CAS  PubMed  Google Scholar 

  21. Cooke JP (2000) Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol 20:2032–2037

    CAS  PubMed  Google Scholar 

  22. Gryglewski RJ, Palmer RM, Moncada S (1986) Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature 320:454–456

    Article  CAS  PubMed  Google Scholar 

  23. Mehta JL, Lopez LM, Chen L, Cox OE (1994) Alterations in nitric oxide synthase activity, superoxide anion generation, and platelet aggregation in systemic hypertension, and effects of celiprolol. Am J Cardiol 74:901–905

    Article  CAS  PubMed  Google Scholar 

  24. Sagar S, Kallo IJ, Kaul N, Ganguly NK, Sharma BK (1992) Oxygen free radicals in essential hypertension. Mol Cell Biochem 111:103–108

    Article  CAS  PubMed  Google Scholar 

  25. Taddei S, Virdis A, Ghiadoni L, Magagna A, Salvetti A (1998) Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension. Circulation 97:2222–2229

    CAS  PubMed  Google Scholar 

  26. Vanhoutte PM, Tang EH (2008) Endothelium-dependent contractions: when a good guy turns bad! J Physiol 586:5295–304

    Article  CAS  PubMed  Google Scholar 

  27. Ferder L, Inserra E, Martinez-Maldonado M (2006) Inflammation and the metabolic syndrome: role of angiotensin II and oxidative stress. Curr Hypertens Rep 8:191–198

    Article  CAS  PubMed  Google Scholar 

  28. Zhang H, Schmeisser A, Garlichs CD, Plötze K, Damme U, Mügge A, Daniel WG (1999) Angiotensin II-induced superoxide anion generation in human vascular endothelial cells: role of membrane-bound NADH-/NADPH-oxidases. Cardiovasc Res 44:215–222

    Article  CAS  PubMed  Google Scholar 

  29. Dohi Y, Hahn AW, Boulanger CM, Bühler FR, Lüscher TF (1992) Endothelin stimulated by angiotensin II augments contractility of spontaneously hypertensive rat resistance arteries. Hypertension 19:131–137

    CAS  PubMed  Google Scholar 

  30. Pollock DM, Keith TL, Highsmith RF (1995) Endothelin receptors and calcium signaling. FASEB J 9:1196–1204

    CAS  PubMed  Google Scholar 

  31. Hoffman A, Abassi ZA, Brodsky S, Ramadan R, Winaver J (2000) Mechanisms of big endothelin-1-induced diuresis and natriuresis: role of ET(B) receptors. Hypertension 35:732–739

    CAS  PubMed  Google Scholar 

  32. Asano H, Shimizu K, Muramatsu M, Iwama Y, Toki Y, Miyazaki Y, Okumura K, Hashimoto H, Ito T (1994) Prostaglandin H2 as an endothelium-derived contracting factor modulates endothelin-1-induced contraction. J Hypertens 12:383–390

    Article  CAS  PubMed  Google Scholar 

  33. Auch-Schwelk W, Vanhoutte PM (1992) Contractions to endothelin in normotensive and spontaneously hypertensive rats: role of endothelium and prostaglandins. Blood Press 1:45–49

    Article  CAS  PubMed  Google Scholar 

  34. Taddei S, Vanhoutte PM (1993) Role of endothelium in endothelin-evoked contractions in the rat aorta. Hypertension 21:9–15

    CAS  PubMed  Google Scholar 

  35. Jankowski V, Tolle M, Vanholder R, Schonfelder G, van der Giet M, Henning L, Schluter H, Paul M, Zidek W, Jankowski J (2005) Uridine adenosine tetraphosphate: a novel endothelium- derived vasoconstrictive factor. Nat Med 11:223–227

    Article  CAS  PubMed  Google Scholar 

  36. Hirao A, Kondo K, Takeuchi K, Inui N, Umemura K, Ohashi K, Watanabe H (2008) Cyclooxygenase-dependent vasoconstricting factor(s) in remodelled rat femoral arteries. Cardiovasc Res 79:161–168

    Article  CAS  PubMed  Google Scholar 

  37. Park SJ, Lee JJ, Vanhoutte PM (1999) Endothelin-1 releases endothelium-derived endoperoxides and thromboxane A2 in porcine coronary arteries with regenerated endothelium. Acta Pharmacol Sin 20:872–878

    CAS  Google Scholar 

  38. Lüscher TF, Vanhoutte PM (1986) Endothelium-dependent contractions to acetylcholine in the aorta of the spontaneously hypertensive rat. Hypertension 8:344–348

    PubMed  Google Scholar 

  39. Gao YJ, Lee RM (2005) Hydrogen peroxide is an endothelium-dependent contracting factor in rat renal artery. Br J Pharmacol 146:1061–1068

    Article  CAS  PubMed  Google Scholar 

  40. Nishimura Y, Usui H, Kurahashi K, Suzuki A (1995) Endothelium-dependent contraction induced by acetylcholine in isolated rat renal arteries. Eur J Pharmacol 275:217–221

    Article  CAS  PubMed  Google Scholar 

  41. Taddei S, Virdis A, Mattei P, Salvetti A (1993) Vasodilation to acetylcholine in primary and secondary forms of human hypertension. Hypertension 21:929–933

    CAS  PubMed  Google Scholar 

  42. Versari D, Daghini E, Virdis A, Ghiadoni L, Taddei S (2009) Endothelium-dependent contractions and endothelial dysfunction in human hypertension. Br J Pharmacol 157:527–536

    Article  CAS  PubMed  Google Scholar 

  43. Tang EH, Leung FP, Huang Y, Feletou 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 151:15–23

    Article  CAS  PubMed  Google Scholar 

  44. Félétou M, Verbeuren TJ, Vanhoutte PM (2009) Endothelium-dependent contractions in SHR: a tale of prostanoid TP and IP receptors. Br J Pharmacol 156:563–574

    Article  PubMed  CAS  Google Scholar 

  45. 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 76:1003–1010

    CAS  PubMed  Google Scholar 

  46. Gluais P, Lonchampt M, Morrow JD, Vanhoutte PM, Feletou M (2005) Acetylcholine-induced endothelium-dependent contractions in the SHR aorta: the Janus face of prostacyclin. Br J Pharmacol 146:834–845

    Article  CAS  PubMed  Google Scholar 

  47. Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, Lipsky PE (1998) Cyclooxygenase in biology and disease. FASEB J 12:1063–1073

    CAS  PubMed  Google Scholar 

  48. 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 41:143–148

    Article  CAS  PubMed  Google Scholar 

  49. Tang EH, Ku DD, Tipoe GL, Feletou 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 46:761–765

    Article  CAS  PubMed  Google Scholar 

  50. 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 104:228–235

    Article  CAS  PubMed  Google Scholar 

  51. 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 29:185–192

    Article  CAS  PubMed  Google Scholar 

  52. 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 32:409–418

    CAS  PubMed  Google Scholar 

  53. Numaguchi Y, Harada M, Osanai H, Hayashi K, Toki Y, Okumura 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 41:682–688

    Article  CAS  PubMed  Google Scholar 

  54. 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–H2264

    Article  CAS  PubMed  Google Scholar 

  55. Gluais P, Vanhoutte PM, Félétou M (2007) Mechanisms underlying ATP-induced endothelium-dependent contractions in the SHR aorta. Eur J Pharmacol 556:107–114

    Article  CAS  PubMed  Google Scholar 

  56. Zou MH, Leist M, Ullrich V (1999) Selective nitration of prostacyclin synthase and defective vasorelaxation in atherosclerotic bovine coronary arteries. Am J Pathol 154:1359–1365

    CAS  PubMed  Google Scholar 

  57. 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 51:198–203

    Article  CAS  PubMed  Google Scholar 

  58. Bachschmid M, Thurau S, Zou MH, Ullrich V (2003) Endothelial cell activation by endotoxin involves superoxide/NO-mediated nitration of prostacyclin synthase and thromboxane receptor stimulation. FASEB J 17:914–916

    CAS  PubMed  Google Scholar 

  59. Dai FX, Skopec J, Diederich A, Diederich D (1992) Prostaglandin H2 and thromboxane A2 are contractile factors in intrarenal arteries of spontaneously hypertensive rats. Hypertension 19:795–798

    CAS  PubMed  Google Scholar 

  60. Auch-Schwelk W, Katusic ZS, Vanhoutte PM (1990) Thromboxane A2 receptor antagonists inhibit endothelium-dependent contractions. Hypertension 15:699–703

    CAS  PubMed  Google Scholar 

  61. 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 15:475–481

    CAS  PubMed  Google Scholar 

  62. 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 136:104–110

    Article  CAS  PubMed  Google Scholar 

  63. Tang EH, Jensen BL, Skott O, Leung GP, Feletou M, Man RY, Vanhoutte PM (2008) The role of prostaglandin E and thromboxane-prostanoid receptors in the response to prostaglandin E2 in the aorta of Wistar Kyoto rats and spontaneously hypertensive rat. Cardiovasc Res 78:130–138

    Article  CAS  PubMed  Google Scholar 

  64. Rapoport RM, Williams SP (1996) Role of prostaglandins in acetylcholine-induced contraction of aorta from spontaneously hypertensive and Wistar-Kyoto rats. Hypertension 28:64–75

    CAS  PubMed  Google Scholar 

  65. Shi Y, Feletou M, Ku DD, Man RY, Vanhoutte PM (2007) The calcium ionophore A23187 induces endothelium-dependent contractions in femoral arteries from rats with streptozotocin-induced diabetes. Br J Pharmacol 150:624–632

    Article  CAS  PubMed  Google Scholar 

  66. Auch-Schwelk W, Katusic ZS, Vanhoutte PM (1989) Contractions to oxygen-derived free radicals are augmented in aorta of the spontaneously hypertensive rat. Hypertension 13:859–864

    CAS  PubMed  Google Scholar 

  67. Li J, Li W, Li W, Altura BT, Altura BM (2004) Mechanisms of hydroxyl radical-induced contraction of rat aorta. Eur J Pharmacol 499:171–178

    Article  CAS  PubMed  Google Scholar 

  68. Rodriguez-Martinez MA, Garcia-Cohen EC, Baena AB, Gonzalez R, Salaices M, Marin J (1998) Contractile responses elicited by hydrogen peroxide in aorta from normotensive and hypertensive rats. Endothelial modulation and mechanism involved. Br J Pharmacol 125:1329–1335

    Article  CAS  PubMed  Google Scholar 

  69. Yang Z, Zheng T, Zhang A, Altura BT, Altura BM (1998) Mechanisms of hydrogen peroxide-induced contraction of rat aorta. Eur J Pharmacol 344:169–181

    Article  CAS  PubMed  Google Scholar 

  70. Tang EH, Vanhoutte PM (2008) Gap junction inhibitors reduce endothelium-dependent contractions in the aorta of spontaneously hypertensive rats. J Pharmacol Exp Ther 327:148–153

    Article  CAS  PubMed  Google Scholar 

  71. Katusic ZS, Vanhoutte PM (1989) Superoxide anion is an endothelium-derived contracting factor. Am J Physiol 257:H33–H37

    CAS  PubMed  Google Scholar 

  72. Neunteufl T, Katzenschlager R, Hassan A, Klaar U, Schwarzacher S, Glogar D, Bauer P, Weidinger F (1997) Systemic endothelial dysfunction is related to the extent and severity of coronary artery disease. Atherosclerosis 129:111–118

    Article  CAS  PubMed  Google Scholar 

  73. Sayed N, Kim DD, Fioramonti X, Iwahashi T, Durán WN, Beuve A (2008) Nitroglycerin-induced S-nitrosylation and desensitization of soluble guanylyl cyclase contribute to nitrate tolerance. Circ Res 103:606–614

    Article  CAS  PubMed  Google Scholar 

  74. Sydow K, Daiber A, Oelze M, Chen Z, August M, Wendt M, Ullrich V, Mülsch A, Schulz E, Keaney JF Jr, Stamler JS, Münzel T (2004) Central role of mitochondrial aldehyde dehydrogenase and reactive oxygen species in nitroglycerin tolerance and cross-tolerance. J Clin Invest 113:482–489

    CAS  PubMed  Google Scholar 

  75. Katusic ZS (2001) Vascular endothelial dysfunction: does tetrahydrobiopterin play a role? Am J Physiol Heart Circ Physiol 281:H981–H986

    CAS  PubMed  Google Scholar 

  76. Vásquez-Vivar J (2009) Tetrahydrobiopterin, superoxide, and vascular dysfunction. Free Radic Biol Med 47:1108–1119

    Article  PubMed  CAS  Google Scholar 

  77. Gokce N (2004) l-Arginine and hypertension. J Nutr 134:2807S–2811S

    CAS  PubMed  Google Scholar 

  78. Lekakis JP, Papathanassiou S, Papaioannou TG, Papamichael CM, Zakopoulos N, Kotsis V, Dagre AG, Stamatelopoulos K, Protogerou A, Stamatelopoulos SF (2002) Oral l-arginine improves endothelial dysfunction in patients with essential hypertension. Int J Cardiol 86:317–323

    Article  PubMed  Google Scholar 

  79. Miller AL (2006) The effects of sustained-release l-arginine formulation on blood pressure and vascular compliance in 29 healthy individuals. Altern Med Rev 11:23–29

    PubMed  Google Scholar 

  80. Auch-Schwelk W, Katusić ZS, Vanhoutte PM (1992) Nitric oxide inactivates endothelium-derived contracting factor in the rat aorta. Hypertension 19:442–445

    CAS  PubMed  Google Scholar 

  81. Feletou M, Tang EH, Vanhoutte PM (2008) Nitric oxide the gatekeeper of endothelial vasomotor control. Front Biosci 13:4198–4217

    Article  CAS  PubMed  Google Scholar 

  82. Tang EH, Feletou M, Huang Y, Man RY, Vanhoutte PM (2005) Acetylcholine and sodium nitroprusside cause long-term inhibition of EDCF-mediated contractions. Am J Physiol Heart Circ Physiol 289:H2434–2440

    Article  CAS  PubMed  Google Scholar 

  83. Yang D, Gluais P, Zhang JN, Vanhoutte PM, Félétou M (2004) Nitric oxide and inactivation of the endothelium-dependent contracting factor released by acetylcholine in spontaneously hypertensive rat. J Cardiovasc Pharmacol 43:815–820

    Article  CAS  PubMed  Google Scholar 

  84. Mancini GB, Henry GC, Macaya C, O'Neill BJ, Pucillo AL, Carere RG, Wargovich TJ, Mudra H, Lüscher TF, Klibaner MI, Haber HE, Uprichard AC, Pepine CJ, Pitt B (1996) Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease. The TREND (Trial on Reversing ENdothelial Dysfunction) Study. Circulation 94:258–265

    CAS  PubMed  Google Scholar 

  85. Taddei S, Virdis A, Ghiadoni L, Sudano I, Salvetti A (2002) Effects of antihypertensive drugs on endothelial dysfunction: clinical implications. Drugs 62:265–284

    Article  CAS  PubMed  Google Scholar 

  86. Godfraind T (2005) Antioxidant effects and the therapeutic mode of action of calcium channel blockers in hypertension and atherosclerosis. Philos Trans R Soc Lond B Biol Sci 360:2259–2272

    Article  CAS  PubMed  Google Scholar 

  87. Batova S, DeWever J, Godfraind T, Balligand JL, Dessy C, Feron O (2006) The calcium channel blocker amlodipine promotes the unclamping of eNOS from caveolin in endothelial cells. Cardiovasc Res 71:478–485

    Article  CAS  PubMed  Google Scholar 

  88. Lenasi H, Kohlstedt K, Fichtlscherer B, Mülsch A, Busse R, Fleming I (2003) Amlodipine activates the endothelial nitric oxide synthase by altering phosphorylation on Ser1177 and Thr495. Cardiovasc Res 59:844–853

    Article  CAS  PubMed  Google Scholar 

  89. van Amsterdam FT, Roveri A, Maiorino M, Ratti E, Ursini F (1992) Lacidipine: a dihydropyridine calcium antagonist with antioxidant activity. Free Radic Biol Med 12:183–187

    Article  PubMed  Google Scholar 

  90. Kalinowski L, Dobrucki LW, Szczepanska-Konkel M, Jankowski M, Martyniec L, Angielski S, Malinski T (2003) Third-generation beta-blockers stimulate nitric oxide release from endothelial cells through ATP efflux: a novel mechanism for antihypertensive action. Circulation 107:2747–2752

    Article  CAS  PubMed  Google Scholar 

  91. Moncada S, Vane JR (1997) The role of prostacyclin in vascular tissue. Fed Proc 38:66–71

    Google Scholar 

  92. Salinas G, Rangasetty UC, Uretsky BF, Birnbaum Y (2007) The cycloxygenase 2 (COX-2) story: it's time to explain, not inflame. J Cardiovasc Pharmacol Ther 12:98–111

    Article  CAS  PubMed  Google Scholar 

  93. Belhassen L, Pelle G, Dubois-Rande J, Adnot S (2003) Improved endothelial function by the thromboxane a2 receptor antagonist S18886 in patients with coronary artery disease treated with aspirin. J Am Coll Cardiol 41:1198–1204

    Article  CAS  PubMed  Google Scholar 

  94. Behm DJ, Ogbonna A, Wu C, Burns-Kurtis CL, Douglas SA (2009) Epoxyeicosatrienoic acids function as selective, endogenous antagonists of native thromboxane receptors: identification of a novel mechanism of vasodilation. J Pharmacol Exp Ther 328:231–239

    Article  CAS  PubMed  Google Scholar 

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  1. Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, 77 Ave Louis Pasteur, NRB741, Boston, MA, 02115, USA

    Eva H. C. Tang

  2. Department Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China

    Paul M. Vanhoutte

  3. Department BIN Fusion Technology, Chonbuk National University, Jeonju, Korea

    Paul M. Vanhoutte

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Correspondence to Eva H. C. Tang.

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Tang, E.H.C., Vanhoutte, P.M. Endothelial dysfunction: a strategic target in the treatment of hypertension?. Pflugers Arch - Eur J Physiol 459, 995–1004 (2010). https://doi.org/10.1007/s00424-010-0786-4

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