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The L-arginine-nitric oxide pathway in hypertension

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Abstract

Nitric oxide is involved in the regulation of resting vascular tone, adaptation of blood flow to metabolic demand of tissue, and adaptation of vessel diameter to volume of inflow, ie, flow-mediated dilation. Arterial hypertension is associated with an increased vascular tone of resistance vessels, a reduced compliance of conduit arteries, along with a thickening of the intima-media leading to vascular remodeling. Dysfunctional endothelium triggers such maladaptive processes. A reduced bioavailability of nitric oxide has been shown in hypertensive individuals dependent on the duration and severity of arterial hypertension. Angiotensin-converting enzyme inhibitors reverse endothelial dysfunction, whereas a concomitant reduction in significant cardiac events due to improved bioavailability has yet to be established. Long-term follow-up studies in individuals with manifest endothelial dysfunction and in offspring from hypertensive patients underscore the prognostic and genetic significance of a reduced nitric oxide bioavailability for the pathophysiology of arterial hypertension.

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References and Recommended Reading

  1. Celermajer DS. Endothelial dysfunction: Does it matter? Is it reversible? J Am Coll Cardiol 1997, 30:325–333.

    Article  PubMed  CAS  Google Scholar 

  2. Bauersachs J, Popp R, Hecker M, et al.: Nitric oxide attenuates the release of endothelium-derived hyperpolarizing factor. Circulation 1996, 94:3341–3347.

    PubMed  CAS  Google Scholar 

  3. Duffy SJ, Castle SF, Harper RW, Meredith IT: Contribution of vasodilator prostanoids and nitric oxide to resting flow, metabolic vasodilation, and flow-mediated dilation in human coronary circulation. Circulation 1999, 100:1951–1957.

    PubMed  CAS  Google Scholar 

  4. Heusch G, Baumgart D, Camici P, et al.: a-adrenergic coronary vasoconstriction and myocardial ischemia in humans. Circulation 2000, 101:689–694.

    PubMed  CAS  Google Scholar 

  5. Kelm M, Feelisch M, Spahr R, et al.: Quantitative and kinetic characterization of nitric oxide and EDRF release from cultured endothelial cells. Biochem Biophys Res Commun 1988, 154:236–244.

    Article  PubMed  CAS  Google Scholar 

  6. Kelm M, Feelisch M, Deussen A, et al.: Release of endothelium derived nitric oxide in relation to pressure and flow. Cardiovasc Res 1991, 25:831–836.

    PubMed  CAS  Google Scholar 

  7. Kelm M, Feelisch M, Krebber T, et al.: Mechanisms of histamininduced coronary vasodilation: H1-receptor-mediated release of endothelium-derived nitric oxide. J Vasc Res 1993, 30:132–138.

    PubMed  CAS  Google Scholar 

  8. Rees DD, Palmer RMJ, Moncada S: Role of endotheliumderived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci U S A 1989, 86:3375–3378.

    Article  PubMed  CAS  Google Scholar 

  9. Kelm M, Schrader J: Control of coronary vascular tone by nitric oxide. Circ Res 1990, 66:1561–1575.

    PubMed  CAS  Google Scholar 

  10. Joannides R, Richard V, Haefeli WE, et al.: Role of basal and stimulated release of nitric oxide in the regulation of radial artery caliber in humans. Hypertension 1995, 26:327–331.

    PubMed  CAS  Google Scholar 

  11. Egashira K, Katsuda Y, Mohri M, et al.: Role of endotheliumderived nitric oxide in coronary vasodilatation induced by pacing tachycardia in humans. Circ Res 1996, 79:331–335.

    PubMed  CAS  Google Scholar 

  12. Hoeffner U, Boulanger C, Vanhoutte PM: Proximal and distal dog coronary arteries respond differently to basal EDRF but not to NO. Am J Physiol Heart Circ Physiol 1989, 256:H828-H831.

    CAS  Google Scholar 

  13. Lefroy DC, Crake T, Uren NG, et al.: Effect of inhibition of nitric oxide synthesis on epicardial coronary artery caliber and coronary blood flow in humans. Circulation 1993, 88:43–54.

    PubMed  CAS  Google Scholar 

  14. Lüscher TF, Diederich D, Stebenmann R, et al.: Difference between endothelium-dependent relaxation in arterial and in venous coronary bypass grafts. N Engl J Med 1988, 319:462–467.

    PubMed  Google Scholar 

  15. Frank MW, Harris KR, Ahlin KA, Klocke FJ: Endotheliumderived relaxing factor (nitric oxide) has a tonic vasodilating action on coronary collateral vessels. J Am Coll Cardiol 1996, 27:658–663.

    Article  PubMed  CAS  Google Scholar 

  16. Bloch W, Hoever D, Addicks K: Stimulation of endogenous NO-production influences the dilation of the capillary microvasculature in vivo. In Biochemical, Pharmacological and Clinical Aspects of Nitric Oxide. Edited by Weissman BA, Allon N, Shapira S. London: Plenum Publishing Company Ltd; 1995:153–160.

    Google Scholar 

  17. Ursell PC, Mayes M: Anatomic distribution of nitric oxide synthase in the heart. Int J Cardiol 1995, 50:217–223.

    Article  PubMed  CAS  Google Scholar 

  18. Andries LJ, Brutsaert DL, Sys SU: Nonuniformity of endothelial constitutive nitric oxide synthase distribution in cardiac endothelium. Circ Res 1998, 82:195–203.

    PubMed  CAS  Google Scholar 

  19. Lauer T, Preik M, Rassaf T, et al.: Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action. Proc Natl Acad Sci U S A 2001, 98:12814–12819. A key paper demonstrating that changes in plasma nitrite reflect changes in eNOS activity and therefore that it is possible to assess changes in eNOS activity in humans by biochemical measures.

    Article  PubMed  CAS  Google Scholar 

  20. Rassaf T, Preik M, Kleinbongard P, et al.: Vasodilator action of aqueous NO solution provides evidence for in vivo transport of bioactive NO in human plasma. J Clin Invest 2002, 109:1241–1248. First report demonstrating that NO is transported in its bioactive form along the vascular tree in humans.

    Article  PubMed  CAS  Google Scholar 

  21. Minamiyama Y, Takemura S, Inoue M: Albumin is an important vascular tonus regulator as a reservoir of nitric oxide. Biochem Biophys Res Commun 1996, 225:112–115.

    Article  PubMed  CAS  Google Scholar 

  22. Lundberg J: Airborne nitric oxide: Inflammatory marker and aerocrine messenger in man. Acta Physiol Scand 1996, 157 (Suppl 633):1–27.

    Google Scholar 

  23. Pelc LR, Gross GJ, Warltier DC: Preferential increase in subendocardial perfusion produced by endothelium-dependent vasodilators. Circulation 1987, 76:191–200.

    PubMed  CAS  Google Scholar 

  24. Chambers JW, Voss GS, Snider JR, et al.: Direct in vivo effects of nitric oxide on the coronary circulation. Am J Physiol Heart Circ Physiol 1996, 271:H1584-H1593.

    CAS  Google Scholar 

  25. Minamino T, Kitakaze M, Matsumura Y, et al.: Impact of coronary risk factors on contribution of nitric oxide and adenosine to metabolic coronary vasodilation in humans. J Am Coll Cardiol 1998, 31:1274–1279.

    Article  PubMed  CAS  Google Scholar 

  26. Quyyumi AA, Dakak N, Andrews NP, et al.: Contribution of nitric oxide to metabolic coronary vasodilation in the human heart. Circulation 1995, 92:320–326.

    PubMed  CAS  Google Scholar 

  27. Pohl U, Holtz J, Busse R, Bassenge E: Crucial role of endothelium in the vasodilator response to increased flow in vivo. Hypertension 1986, 8:37–44.

    PubMed  CAS  Google Scholar 

  28. Rubanyi GM, Romero JC, Vanhoutte PM: Flow-induced release of endothelium-derived relaxing factor. Am J Physiol Heart Circ Physiol 1986, 250:H1145-H1149.

    CAS  Google Scholar 

  29. Holtz J, Förstermann U, Pohl U, et al.: Flow-dependent, endothelium-mediated dilation of epicardial coronary arteries in conscious dogs: Effects of cyclooxygenase inhibition. J Cardiovasc Pharmacol 1984, 6:1161–1169.

    Article  PubMed  CAS  Google Scholar 

  30. Inoue T, Tomoike H, Hisano K, Nakamura M: Endothelium determines flow-dependent dilation of the epicardial coronary artery in dogs. J Am Coll Cardiol 1988, 11:187–191.

    PubMed  CAS  Google Scholar 

  31. Bevan JA, Joyce EH, Wellman GC: Flow-dependent dilation in a resistance artery still occurs after endothelium removal. Circ Res 1988, 63:980–985.

    PubMed  CAS  Google Scholar 

  32. Hull SS Jr, Kaiser L, Jaffe MD, Sparks HV Jr: Endotheliumdependent flow-induced dilation of canine femoral and saphenous arteries. Blood Vess 1986, 23:183–198.

    Google Scholar 

  33. Miura H, Wachtel RE, Liu Y, et al.: Flow-induced dilation of human coronary arterioles. Important role of Ca2+-activated K+ channels. Circulation 2001, 103:1992–1998.

    PubMed  CAS  Google Scholar 

  34. Joannides R, Haefeli WE, Linder L, et al.: Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. Circulation 1995, 91:1314–1319.

    PubMed  CAS  Google Scholar 

  35. Bevan JA: Flow regulation of vascular tone. Its sensitivity to changes in sodium and calcium. Hypertension 1993, 22:273–281.

    PubMed  CAS  Google Scholar 

  36. Shechter M, Sharir M, Labrador MJP, et al.: Oral magnesium therapy improves endothlial function in patients with coronary artery disease. Circulation 2000, 102:2353–2358.

    PubMed  CAS  Google Scholar 

  37. Niebauer J, Cooke JP: Cardiovascular effects of exercise: role of endothelial shear stress. J Am Coll Cardiol 1996, 28:1652–1660.

    Article  PubMed  CAS  Google Scholar 

  38. Mullen MJ, Kharbanda RK, Cross J, et al.: Heterogenous nature of flow-mediated dilatation in human conduit arteries in vivo. Circ Res 2001, 88:145–151.

    PubMed  CAS  Google Scholar 

  39. Dimmeler S, Fleming I, Fisslthaler B, et al.: Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 1999, 399:601–605.

    Article  PubMed  CAS  Google Scholar 

  40. Clarkson P, Montgomery HE, Mullen MJ, et al.: Exercise training enhances endothelial function in young men. J Am Coll Cardiol 1999, 33:1379–1385.

    Article  PubMed  CAS  Google Scholar 

  41. Quyyumi AA: Endothelial function in health and disease: new insights into the genesis of cardiovascular disease. Am J Med 1998, 105:32S-39S.

    Article  PubMed  CAS  Google Scholar 

  42. Sessa WC, Pritchard K, Seyedi N, et al.: Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression. Circ Res 1994, 74:349–353.

    PubMed  CAS  Google Scholar 

  43. Zeiher AM, Drexler H, Saurbier B, Just H: Endothelium-mediated coronary blood flow modulation in humans. J Clin Invest 1993, 92:652–662.

    Article  PubMed  CAS  Google Scholar 

  44. Zeiher AM, Drexler H, Wollschläger H, Just H: Modulation of coronary vasomotor tone in humans. Progressive endothelial dysfunction with different early stages of atherosclerosis. Circulation 1991, 83:391–401.

    PubMed  CAS  Google Scholar 

  45. Fukai T, Siegfried MR, Ushio-Fukai M, et al.: Regulation of the vascular extracellular superoxide dismutase by nitric oxide and exercise training. J Clin Invest 2000, 105:1631–1639.

    PubMed  CAS  Google Scholar 

  46. Ruschitzka FT, Wenger RH, Stallmach T, et al.: Nitric oxide prevents cardiovascular disease and determines survival in polyglobulic mice overexpressing erythropoietin. Proc Natl Acad Sci U S A 2000, 97:11609–11613. An experimental study that underscores the crucial role of NO for the interaction of the vascular endothelium and blood cells.

    Article  PubMed  CAS  Google Scholar 

  47. Cooke JP, Dzau VJ: Derangements of the nitric oxide synthase pathway, L-arginine, and cardiovascular diseases. Circulation 1997, 96:379–382.

    PubMed  CAS  Google Scholar 

  48. Cosentino F, Katusic ZS: Tetrahydrobiopterin and dysfunction of endothelial nitric oxide synthase in coronary arteries. Circulation 1995, 91:139–144.

    PubMed  CAS  Google Scholar 

  49. Kelm M, Dahmann R, Wink D, Feelisch M: The nitric oxide-superoxide assay: insights into the biological chemistry of the O2/NO-interaction. J Biol Chem 1997, 272(15):9922–9932.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  51. Traber MG, Sies H.:Vitamin E in humans: demand and delivery. Ann Rev Nutr 1996, 16:321–347.

    Article  CAS  Google Scholar 

  52. McCall MR, Frei B: Can antioxidant vitamins materially reduce oxidative damage in humans? Free Radic Biol Med 1999, 26:1034–1053.

    Article  PubMed  CAS  Google Scholar 

  53. Spencer AP, Carson DS, Crouch MA: Vitamin E and coronary artery disease. Arch Intern Med 1999, 159:1313–1320.

    Article  PubMed  CAS  Google Scholar 

  54. Kelm M, Feelisch M, Krebber T, et al.: Role of nitric oxide in the regulation of coronary vascular tone in hearts from hypertensive rats. Maintenance of nitric oxide-forming capacity and increased basal production of nitric oxide. Hypertension 1995, 25:186–193.

    PubMed  CAS  Google Scholar 

  55. Kelm M: Kardiovaskuläre Wirkungen von Stickstoffmoxid und ihre Bedeutung für die arterielle Hypertonie. Stuttgart-New York: Schattauer Verlag; 1996.

    Google Scholar 

  56. Nava E, Noll G, Lüscher TF: Increased activity of constitutive nitric oxide synthase in cardiac endothelium in spontaneous hypertension. Circulation 1995, 91:2310–2313.

    PubMed  CAS  Google Scholar 

  57. Taddei S, Virdis A, Ghiadoni L, Salvetti A: Endothelial dysfunction in hypertension: fact or fancy? J Cardiovasc Pharmacol 1998, 32(Suppl 3):S41-S47.

    PubMed  CAS  Google Scholar 

  58. Kelm M, Preik M, Hafner D, Strauer BE: Evidence for a multifactorial process involved in the impaired flow response to nitric oxide in hypertensive patients with endothelial dysfunction. Hypertension 1996, 27:346–353.

    PubMed  CAS  Google Scholar 

  59. Feelisch M, Kelm M: Biotransformation of organic nitrates to nitric oxide by vascular smooth muscle and endothelial cells. Biochem Biophys Res Commun 1991, 180:286–293.

    Article  PubMed  CAS  Google Scholar 

  60. Quyyumi AA, Mulcahy D, Andrews NP, et al.: Coronary vascular nitric oxide activity in hypertension and hypercholesterolemia. Comparison of acetylcholine and substance P. Circulation 1997, 95:104–110.

    PubMed  CAS  Google Scholar 

  61. Antony I, Lerebours G, Nitenberg A: Loss of flow-dependent coronary artery dilatation in patients with hypertension. Circulation 1995, 91:1624–1628.

    PubMed  CAS  Google Scholar 

  62. Frielingsdorf J, Kaufmann P, Seiler C, et al.: Abnormal coronary vasomotion in hypertension: role of coronary artery disease. J Am Coll Cardiol 1996, 28:935–941.

    Article  PubMed  CAS  Google Scholar 

  63. Houghton JL, Davison CA, Kuhner PA, et al.: Heterogeneous vasomotor responses of coronary conduit and resistance vessels in hypertension. J Am Coll Cardiol 1998, 31:374–382.

    Article  PubMed  CAS  Google Scholar 

  64. Ruschitzka FT, Corti R, Noll G, Lüscher TF: A rationale for treatment of endothelial dysfunction in hypertension. J Hypertens 1999, 17(Suppl 1):S25-S35.

    CAS  Google Scholar 

  65. Ruschitzka FT, Noll G, Lüscher TF: Combination of ACE inhibitors and calcium antagonists: a logical approach. J Cardiovasc Pharmacol 1998, 31(Suppl 2):S5-S16.

    Article  PubMed  CAS  Google Scholar 

  66. Yusuf S, Sleight P, Pogue J, et al.: Heart Outcomes Prevention Evaluation Study Investigators: Effects of an angiotensinconverting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000, 342:145–153.

    Article  PubMed  CAS  Google Scholar 

  67. Kuga T, Mohri M, Egashira K, et al.: Bradykinin-induced vasodilation of human coronary arteries in vivo: role of nitric oxide and angiotensin-converting enzyme. J Am Coll Cardiol 1997, 30:108–112.

    Article  PubMed  CAS  Google Scholar 

  68. Usui M, Egashira K, Tomita H, et al.: Important role of local angiotensin II activity mediated via type 1 receptor in the pathogenesis of cardiovascular inflammatory changes induced by chronic blockade of nitric oxide synthesis in rats. Circulation 2000, 101:305–311.

    PubMed  CAS  Google Scholar 

  69. Mancini GBJ: Role of angiotensin-converting enzyme inhibition in reversal of endothelial dysfunction in coronary artery disease. Am J Med 1998, 105(1A):40S-47S.

    Article  PubMed  CAS  Google Scholar 

  70. Cannon RO III: Potential mechanisms for the effect of angiotensin-converting enzyme inhibitors on endothelial dysfunction: the role of nitric oxide. Am J Cardiol 1998, 82(Suppl 10A):8S-10S.

    PubMed  CAS  Google Scholar 

  71. Antony I, Lerebours G, Nitenberg A: Angiotensin-converting enzyme inhibition restores flow-dependent and cold pressor test-induced dilations in coronary arteries of hypertensive patients. Circulation 1996, 94:3115–3122.

    PubMed  CAS  Google Scholar 

  72. Prasad A, Husain S, Quyyumi AA: Abnormal flow-mediated epicardial vasomotion in human coronary arteries is improved by angiotensin-converting enzyme inhibition. A potential role of bradykinin. J Am Coll Cardiol 1999, 33:796–804.

    Article  PubMed  CAS  Google Scholar 

  73. Mancini GBJ, Henry GC, Macaya C, et al.: 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 1996, 94:258–265.

    PubMed  CAS  Google Scholar 

  74. Pitt B, Byrington RP, Furberg CD, et al.: Effect of amlodipine on the progression of atherosclerosis and the occurrence of clinical events. Circulation 2000, 102:1503–1510.

    PubMed  CAS  Google Scholar 

  75. Frielingsdorf J, Seiler C, Kaufmann P, et al.: Normalization of abnormal coronary vasomotion by calcium antagonists in patients with hypertension. Circulation 1996, 93:1380–1387.

    PubMed  CAS  Google Scholar 

  76. Kaufmann PA, Frielingsdorf J, Mandinov L, et al.: Reversal of abnormal coronary vasomotion by calcium antagonists in patients with hypercholesterolemia. Circulation 1998, 97:1348–1354.

    PubMed  CAS  Google Scholar 

  77. Kitakaze M, Asanuma H, Takashima S, et al.: Nifedipineinduced coronary vasodilation in ischemic hearts is attributable to bradykinin- and NO-dependent mechanisms in dogs. Circulation 2000, 101:311–317.

    PubMed  CAS  Google Scholar 

  78. Verhaar MC, Honing MLH, van Dam T, et al.: Nifedipine improves endothelial function in hyperchloesterolemia, independently of an effect on blood pressure or plasma lipids. Cardiovasc Res 1999, 42:752–760.

    Article  PubMed  CAS  Google Scholar 

  79. Zhang X, Recchia FA, Bernstein R, et al.: Kinin-mediated coronary nitric oxide production contributes to the therapeutic action of angiotensin-converting enzyme and neutral endopeptidase inhibitors and amlodipine in the treatment in heart failure. J Pharmacol Exp Ther 1999, 288:742–751.

    PubMed  CAS  Google Scholar 

  80. Kobayashi N, Yanaka H, Tojo A, et al.: Effects of amlodipine on nitric oxide synthase mRNA expression and coronary microcirculation in prolonged nitric oxide blockade-induced hypertensive rats. J Cardiovasc Pharmacol 1999, 34:173–181.

    Article  PubMed  CAS  Google Scholar 

  81. Kitakaze M, Node K, Minamino T, et al.: A Ca channel blocker, benidipine, increases coronary blood flow and attenuates the severity of myocardial ischemia via NO-dependent mechanisms in dogs. J Am Coll Cardiol 1999, 33:242–249.

    Article  PubMed  CAS  Google Scholar 

  82. Ruschitzka FT, Lüscher TF: Is there a rationale for combining angiotensin-converting enzyme inhibitors and calcium antagonists in cardiovascular disease?. Am Heart J 1997, 134:S31-S47.

    Article  PubMed  CAS  Google Scholar 

  83. Parent R, Al-Obaidi M, Lavallee M: Nitric oxide formation contributes to adrenergic dilation of resistance coronary vessels in conscious dogs. Circ Res 1993, 73:241–251.

    PubMed  CAS  Google Scholar 

  84. Dandona P, Karne R, Ghanim H, et al.: Carvedilol inhibits reactive oxygen species generation by leukocytes and oxidative damage to amino acids. Circulation 2000, 101:122–124.

    PubMed  CAS  Google Scholar 

  85. Heitzer T, Schlinzig T, Krohn K, et al.: Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation 2001, 104:2673–2678.

    PubMed  CAS  Google Scholar 

  86. Perticone F, Ceravolo R, Pujia A, et al.: Prognostic significance of endothelial dysfunction in hypertensive patients. Circulation 2001, 104:191–196.

    PubMed  CAS  Google Scholar 

  87. Schächinger V, Britten MB, Zeiher AM: Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation 2000, 101:1899–1906. First report on the prognostic significance of endothelial and smooth muscle dysfunction in epicardial arteries, underscoring the significance of arterial hypertension.

    PubMed  Google Scholar 

  88. Suwaidi JA, Hamasaki S, Higano ST, et al.: Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation 2000, 101:948–954. First report demonstrating that patients with dysfunction in the coronary microvasculature are prone to an increased risk of major cardiac events.

    PubMed  CAS  Google Scholar 

  89. Schächinger V, Britten MB, Zeiher AM: Impaired epicardial coronary vasoreactivity predicts for adverse cardiovascular events during long-term follow-up. Circulation 1999, 100 (Suppl I):I-54.

    Google Scholar 

  90. Bonnardeaux A, Nadaud S, Charru A, et al.: Lack of evidence for linkage of the endothelial cell nitric oxide synthase gene to essential hypertension. Circulation 1995, 91:96–102.

    PubMed  CAS  Google Scholar 

  91. Glenn CL, Wang WYS, Morris BJ: Different frequencies of inducible nitric oxide synthase genotypes in older hypertensives. Hypertension 1999, 33:927–932.

    PubMed  CAS  Google Scholar 

  92. Kato N, Sugiyama T, Morita H, et al.: Lack of evidence for association between the endothelial nitric oxide synthase gene and hypertension. Hypertension 1999, 33:933–936.

    PubMed  CAS  Google Scholar 

  93. Cox DA, Vita JA, Treasure CB, et al.: Atherosclerosis impairs flow-mediated dilation of coronary arteries in humans. Circulation 1989, 80:458–465.

    PubMed  CAS  Google Scholar 

  94. Clarkson P, Celermajer DS, Powe AJ, et al.: Endotheliumdependent dilatation is impaired in young healthy subjects with a family history of premature coronary disease. Circulation 1997, 96:3378–3383.

    PubMed  CAS  Google Scholar 

  95. Gaeta G, De Michele M, Cuomo S, et al.: Arterial abnormalities in the offspring of patients with premature myocardial infarction. N Engl J Med 2000, 343:840–846.

    Article  PubMed  CAS  Google Scholar 

  96. Taddei S, Virdis A, Mattei P, et al.: Defective L-arginine-nitric oxide pathway in offspring of essential hypertensive patients. Circulation 1996, 94:1298–1303.

    PubMed  CAS  Google Scholar 

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Kelm, M. The L-arginine-nitric oxide pathway in hypertension. Current Science Inc 5, 80–86 (2003). https://doi.org/10.1007/s11906-003-0015-z

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