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Racial Differences in Nitric Oxide—Dependent Vasorelaxation

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Abstract

Along with the growing heterogeneity of the American population, ethnic/racial disparity is becoming a clear health issue in the United States. The awareness of ethnic/racial disparities has been growing because of considerable data gathered from recent clinical and epidemiological studies. These studies have highlighted the importance of addressing these differences in the diagnosis and treatment of various diseases potentially according to race. It is becoming particularly clear that there is a 2- to 3-fold racial difference in certain cardiovascular diseases (eg, preeclampsia) associated with dysfunctional nitric oxide—mediated vasodilation. In this review, the authors summarize the current literature on racial disparities in nitric oxide—mediated vasodilation in relation to cardiovascular health with an emphasis on vascular nitric oxide bioavailability as a balance between production via endothelial nitric oxide synthase and degradation through reactive oxygen species. The major hypotheses postulated on the biological basis of these differences are also highlighted.

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References

  1. Furchgott RF, Zawadzki JV The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288:373–376.

    Article  CAS  PubMed  Google Scholar 

  2. Stuart-Smith K. Demystified: nitric oxide. Mol Pathol. 2002;55:360–366.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. 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 U S A. 1987;84:9265–9269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kubes P., Suzuki M., Granger DN Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci USA. 1991;88:4651–4655.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. 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.

    Article  CAS  PubMed  Google Scholar 

  6. Garg UC, Hassid A. Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest. 1989;83:1774–1777.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Contestabile A., Ciani E. Role of nitric oxide in the regulation of neuronal proliferation, survival and differentiation. Neurochem Int. 2004;45:903–914.

    Article  CAS  PubMed  Google Scholar 

  8. Toda N., Ayajiki K., Okamura T. Nitric oxide and penile erectile function. Pharmacol Ther. 2005;106:233–266.

    Article  CAS  PubMed  Google Scholar 

  9. Scherrer U., Sartori C. Defective nitric oxide synthesis: a link between metabolic insulin resistance, sympathetic overactivity and cardiovascular morbidity. Eur J Endocrinol. 2000;142: 315–323.

    Article  CAS  PubMed  Google Scholar 

  10. Keeble JE, Moore PK Pharmacology and potential therapeutic applications of nitric oxide-releasing non-steroidal antiinflammatory and related nitric oxide-donating drugs. Br J Pharmacol. 2002;137:295–310.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Tuteja N., Chandra M., Tuteja R., Misra MK Nitric oxide as a unique bioactive signaling messenger in physiology and pathophysiology. J Biomed Biotechnol. 2004;2004:227–237.

    Google Scholar 

  12. Rauhala P., Andoh T., Chiueh CC Neuroprotective properties of nitric oxide and S-nitrosoglutathione. Toxicol Appl Pharmacol. 2005;207:91–95.

    Article  PubMed  CAS  Google Scholar 

  13. de la Torre JC, Aliev G. Inhibition of vascular nitric oxide after rat chronic brain hypoperfusion: spatial memory and immunocytochemical changes. J Cereb Blood Flow Metab. 2005;25:663–672.

    Article  PubMed  CAS  Google Scholar 

  14. Ricciardolo FL Multiple roles of nitric oxide in the airways. Thorax. 2003;58:175–182.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kawashima S., Yokoyama M. Dysfunction of endothelial nitric oxide synthase and atherosclerosis. Arterioscler Thromb Vasc Biol. 2004;24:998–1005.

    Article  CAS  PubMed  Google Scholar 

  16. Maiorana A., O’Driscoll G., Taylor R., Green D. Exercise and the nitric oxide vasodilator system. Sports Med. 2003;33:1013–1035.

    Article  PubMed  Google Scholar 

  17. Brunner H., Cockcroft JR, Deanfield J., et al.Endothelial function and dysfunction. Part II: association with cardiovascular risk factors and diseases. A statement by the Working Group on Endothelins and Endothelial Factors of the European Society of Hypertension. J Hypertens. 2005;23:233–246.

    Article  CAS  PubMed  Google Scholar 

  18. Lapu-Bula R., Ofili E. From hypertension to heart failure: role of nitric oxide-mediated endothelial dysfunction and emerging insights from myocardial contrast echocardiography. Am J Cardiol. 2007;99:7D–14D.

    Article  CAS  PubMed  Google Scholar 

  19. Miwa K., Fujita M., Sasayama S. Recent insights into the mechanisms, predisposing factors, and racial differences of coronary vasospasm. Heart Vessels. 2005;20:1–7.

    Article  PubMed  Google Scholar 

  20. Hart CM Nitric oxide in adult lung disease. Chest. 1999;115:1407–1417.

    Article  CAS  PubMed  Google Scholar 

  21. Buhimschi IA, Saade GR, Chwalisz K., Garfield RE The nitric oxide pathway in pre-eclampsia: pathophysiological implications. Hum Reprod Update. 1998;4:25–42.

    Article  CAS  PubMed  Google Scholar 

  22. Hajjar I., Kotchen TA Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988–2000. JAMA. 2003;290:199–206.

    Article  PubMed  Google Scholar 

  23. Schocken DD, Arrieta MI, Leaverton PE, Ross EA Prevalence and mortality rate of congestive heart failure in the United States. J Am Coll Cardiol. 1992;20:301–306.

    Article  CAS  PubMed  Google Scholar 

  24. Alderman MH, Cohen HW, Madhavan S. Myocardial infarction in treated hypertensive patients: the paradox of lower incidence but higher mortality in young blacks compared with whites. Circulation. 2000;101:1109–1114.

    Article  CAS  PubMed  Google Scholar 

  25. Kissela B., Schneider A., Kleindorfer D., et al. Stroke in a biracial population: the excess burden of stroke among blacks. Stroke. 2004;35:426–431.

    Article  PubMed  Google Scholar 

  26. Bragulat E., de la Sierra A., Antonio MT, Coca A. Endothelial dysfunction in salt-sensitive essential hypertension. Hypertension. 2001;37:444–448.

    Article  CAS  PubMed  Google Scholar 

  27. McDaniel M., Paxson C., Waldfogel J. Racial disparities in childhood asthma in the United States: evidence from the National Health Interview Survey, 1997 to 2003. Pediatrics. 2006;117:e868–e877.

    Article  PubMed  Google Scholar 

  28. McBean AM, Li S., Gilbertson DT, Collins AJ Differences in diabetes prevalence, incidence, and mortality among the elderly of four racial/ethnic groups: whites, blacks, Hispanics, and Asians. Diabetes Care. 2004;27:2317–2324.

    Article  PubMed  Google Scholar 

  29. Ferdinand KC, Clark LT The epidemic of diabetes mellitus and the metabolic syndrome in African Americans. Rev Cardiovasc Med. 2004;5(suppl 3):S28–S33.

    PubMed  Google Scholar 

  30. McKeigue PM, Shah B., Marmot MG Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians. Lancet. 1991;337: 382–386.

    Article  CAS  PubMed  Google Scholar 

  31. Balarajan R. Ethnic differences in mortality from ischaemic heart disease and cerebrovascular disease in England and Wales. BMJ. 1991;302:560–564.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Benjamin IJ, Arnett DK, Loscalzo J. Discovering the full spectrum of cardiovascular disease: Minority Health Summit 2003: report of the Basic Science Writing Group. Circulation. 2005;111:e120–e123.

    Article  PubMed  Google Scholar 

  33. Alderton WK, Cooper CE, Knowles RG Nitric oxide synthases: structure, function and inhibition. Biochem J. 2001; 357:593–615.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Forstermann U., Gath I., Schwarz P., Closs EI, Kleinert H. Isoforms of nitric oxide synthase: properties, cellular distribution and expressional control. Biochem Pharmacol. 1995;50: 1321–1332.

    Article  CAS  PubMed  Google Scholar 

  35. Kone BC Protein-protein interactions controlling nitric oxide synthases. Acta Physiol Scand. 2000;168:27–31.

    Article  CAS  PubMed  Google Scholar 

  36. Fulton D., Gratton JP, Sessa WC Post-translational control of endothelial nitric oxide synthase: why isn’t calcium/calmodulin enough? J Pharmacol Exp Ther. 2001;299:818–824.

    CAS  PubMed  Google Scholar 

  37. Minshall RD, Sessa WC, Stan RV, Anderson RG, Malik AB Caveolin regulation of endothelial function. Am J Physiol Lung Cell Mol Physiol. 2003;285:L1179–L1183.

    Article  CAS  PubMed  Google Scholar 

  38. Mount PF, Kemp BE, Power DA Regulation of endothelial and myocardial NO synthesis by multi-site eNOS phosphorylation. J Mol Cell Cardiol. 2007;42:271–279.

    Article  CAS  PubMed  Google Scholar 

  39. Fulton D., Gratton JP, McCabe TJ, et al. Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature. 1999;399:597–601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Chen ZP, Mitchelhill KI, Michell BJ, et al. AMP-activated protein kinase phosphorylation of endothelial NO synthase. FEBS Lett. 1999;443:285–289.

    Article  CAS  PubMed  Google Scholar 

  41. Butt E., Bernhardt M., Smolenski A., et al. Endothelial nitric-oxide synthase (type III) is activated and becomes calcium independent upon phosphorylation by cyclic nucleotide-dependent protein kinases.JBiol Chem. 2000;275:5179–5187.

    Article  CAS  Google Scholar 

  42. Michell BJ, Chen Z., Tiganis T., et al. Coordinated control of endothelial nitric-oxide synthase phosphorylation by protein kinase C and the cAMP-dependent protein kinase. J Biol Chem. 2001;276:17625–17628.

    Article  CAS  PubMed  Google Scholar 

  43. Haynes MP, Russell KS, Bender JR Molecular mechanisms of estrogen actions on the vasculature. J Nucl Cardiol. 2000;7: 500–508.

    Article  CAS  PubMed  Google Scholar 

  44. Hafezi-Moghadam A., Simoncini T., Yang Z., et al. Acute cardiovascular protective effects of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase. Nat Med. 2002;8:473–479.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Montagnani M., Chen H., Barr VA, Quon MJ Insulin-stimulated activation of eNOS is independent of Ca2+ but requires phosphorylation by Akt at Ser(1179). J Biol Chem. 2001;276:30392–30398.

    Article  CAS  PubMed  Google Scholar 

  46. Michell BJ, Griffiths JE, Mitchelhill KI, et al. The Akt kinase signals directly to endothelial nitric oxide synthase. Curr Biol. 1999;9:845–848.

    Article  CAS  PubMed  Google Scholar 

  47. Dimmeler S., Assmus B., Hermann C., Haendeler J., Zeiher AM Fluid shear stress stimulates phosphorylation of Akt in human endothelial cells: involvement in suppression of apoptosis. Circ Res. 1998;83:334–341.

    Article  CAS  PubMed  Google Scholar 

  48. Dimmeler S., Fleming I., Fisslthaler B., Hermann C., Busse R., Zeiher AM Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature. 1999;399: 601–605.

    Article  CAS  PubMed  Google Scholar 

  49. Rahman I., Biswas SK, Kode A. Oxidant and antioxidant balance in the airways and airway diseases. Eur J Pharmacol. 2006; 533:222–239.

    Article  CAS  PubMed  Google Scholar 

  50. Mates JM Effects of antioxidant enzymes in the molecular control of reactive oxygen species toxicology. Toxicology. 2000;153:83–104.

    Article  CAS  PubMed  Google Scholar 

  51. Giordano FJ Oxygen, oxidative stress, hypoxia, and heart failure. J Clin Invest. 2005;115:500–508.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Griendling KK, FitzGerald GA Oxidative stress and cardiovascular injury: part I: basic mechanisms and in vivo monitoring of ROS. Circulation. 2003;108:1912–1916.

    Article  PubMed  Google Scholar 

  53. Griendling KK, FitzGerald GA Oxidative stress and cardiovascular injury: part II: animal and human studies. Circulation. 2003;108:2034–2040.

    Article  PubMed  Google Scholar 

  54. Roberts JM, Hubel CA Oxidative stress in preeclampsia. Am J Obstet Gynecol. 2004;190:1177–1178.

    Article  PubMed  Google Scholar 

  55. Myatt L., Cui X. Oxidative stress in the placenta. Histochem Cell Biol. 2004;122:369–382.

    Article  CAS  PubMed  Google Scholar 

  56. Hare JM Nitroso-redox balance in the cardiovascular system. N Engl J Med. 2004;351:2112–2114.

    Article  CAS  PubMed  Google Scholar 

  57. Kozak AJ, Liu F., Funovics P., Jacoby A., Kubant R., Malinski T. Role of peroxynitrite in the process of vascular tone regulation by nitric oxide and prostanoids—a nanotechnological approach. Prostaglandins Leukot Essent Fatty Acids. 2005;72:105–113.

    Article  CAS  PubMed  Google Scholar 

  58. Forstermann U., Closs EI, Pollock JS, et al. Nitric oxide synthase isozymes: characterization, purification, molecular cloning, and functions. Hypertension. 1994;23:1121–1131.

    Article  CAS  PubMed  Google Scholar 

  59. Wang SZ, Zhu SZ, el-Fakahany EE Efficient coupling of m5 muscarinic acetylcholine receptors to activation of nitric oxide synthase. J Pharmacol Exp Ther. 1994;268:552–557.

    CAS  PubMed  Google Scholar 

  60. Harris MB, Ju H., Venema VJ, et al. Reciprocal phosphorylation and regulation of endothelial nitric-oxide synthase in response to bradykinin stimulation. J Biol Chem. 2001;276: 16587–16591.

    Article  CAS  PubMed  Google Scholar 

  61. Isenovic E., Walsh MF, Muniyappa R., Bard M., Diglio CA, Sowers JR Phosphatidylinositol 3-kinase may mediate isoproterenol-induced vascular relaxation in part through nitric oxide production. Metabolism. 2002;51:380–386.

    Article  CAS  PubMed  Google Scholar 

  62. Ito Y., Kitamura K., Kuriyama H. Effects of acetylcholine and catecholamines on the smooth muscle cell of the porcine coronary artery. J Physiol. 1979;294:595–611.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Tagawa T., Imaizumi T., Endo T., Shiramoto M., Harasawa Y., Takeshita A. Role of nitric oxide in reactive hyperemia in human forearm vessels. Circulation. 1994;90:2285–2290.

    Article  CAS  PubMed  Google Scholar 

  64. Dakak N., Husain S., Mulcahy D., et al. Contribution of nitric oxide to reactive hyperemia: impact of endothelial dysfunction. Hypertension. 1998;32:9–15.

    Article  CAS  PubMed  Google Scholar 

  65. Dietz NM, Rivera JM, Eggener SE, Fix RT, Warner DO, Joyner MJ Nitric oxide contributes to the rise in forearm blood flow during mental stress in humans. J Physiol. 1994; 480(pt 2):361–368.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Cardillo C., Kilcoyne CM, Quyyumi AA, Cannon RO III, Panza JA Role of nitric oxide in the vasodilator response to mental stress in normal subjects. Am J Cardiol. 1997;80: 1070–1074.

    Article  CAS  PubMed  Google Scholar 

  67. Endo T., Imaizumi T., Tagawa T., Shiramoto M., Ando S., Takeshita A. Role of nitric oxide in exercise-induced vasodilation of the forearm. Circulation. 1994;90:2886–2890.

    Article  CAS  PubMed  Google Scholar 

  68. Bassett DR Jr, Duey WJ, Walker AJ, Howley ET, Bond V. Racial differences in maximal vasodilatory capacity of forearm resistance vessels in normotensive young adults. Am J Hypertens. 1992;5:781–786.

    Article  PubMed  Google Scholar 

  69. Lang CC, Stein CM, Brown RM, et al. Attenuation of isoproterenol-mediated vasodilatation in blacks. N Engl J Med. 1995;333:155–160.

    Article  CAS  PubMed  Google Scholar 

  70. Hinderliter AL, Sager AR, Sherwood A., Light KC, Girdler SS, Willis PW Ethnic differences in forearm vasodilator capacity. Am J Cardiol. 1996;78:208–211.

    Article  CAS  PubMed  Google Scholar 

  71. Bond V. Jr, Thompson GD, Franks BD, Tearney RJ, Adams RG, Vaccaro P. Racial differences in minimum lower leg vascular resistance in normotensive young adults with positive and negative parental histories of hypertension. J Cardiovasc Risk. 1996;3:423–426.

    Article  PubMed  Google Scholar 

  72. Stein CM, Lang CC, Nelson R., Brown M., Wood AJ Vasodilation in black Americans: attenuated nitric oxide-mediated responses. Clin Pharmacol Ther. 1997;62:436–443.

    Article  CAS  PubMed  Google Scholar 

  73. Cardillo C., Kilcoyne CM, Cannon RO III, Panza JA Racial differences in nitric oxide—mediated vasodilator response to mental stress in the forearm circulation. Hypertension. 1998; 31:1235–1239.

    Article  CAS  PubMed  Google Scholar 

  74. Cardillo C., Kilcoyne CM, Cannon RO III, Panza JA Attenuation of cyclic nucleotide-mediated smooth muscle relaxation in blacks as a cause of racial differences in vasodilator function. Circulation. 1999;99:90–95.

    Article  CAS  PubMed  Google Scholar 

  75. Jones DS, Andrawis NS, Abernethy DR Impaired endothelial-dependent forearm vascular relaxation in black Americans. Clin Pharmacol Ther. 1999;65:408–412.

    Article  CAS  PubMed  Google Scholar 

  76. Stein CM, Lang CC, Singh I., He HB, Wood AJ Increased vascular adrenergic vasoconstriction and decreased vasodilation in blacks: additive mechanisms leading to enhanced vascular reactivity. Hypertension. 2000;36:945–951.

    Article  CAS  PubMed  Google Scholar 

  77. Gainer JV, Stein CM, Neal T., Vaughan DE, Brown NJ Interactive effect of ethnicity and ACE insertion/deletion polymorphism on vascular reactivity. Hypertension. 2001;37:46–51.

    Article  CAS  PubMed  Google Scholar 

  78. Rosenbaum DA, Pretorius M., Gainer JV, et al. Ethnicity affects vasodilation, but not endothelial tissue plasminogen activator release, in response to bradykinin. Arterioscler Thromb Vasc Biol. 2002;22:1023–1028.

    Article  CAS  PubMed  Google Scholar 

  79. Duck MM, Hoffman RP Impaired endothelial function in healthy African-American adolescents compared with Caucasians. J Pediatr. 2007;150:400–406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Kahn DF, Duffy SJ, Tomasian D., et al. Effects of black race on forearm resistance vessel function. Hypertension. 2002;40: 195–201.

    Article  CAS  PubMed  Google Scholar 

  81. Androne AS, Hryniewicz K., Hudaihed A., et al. Comparison of metabolic vasodilation in response to exercise and ischemia and endothelium-dependent flow-mediated dilation in African-American versus non-African-American patients with chronic heart failure. Am J Cardiol. 2006;97:685–689.

    Article  PubMed  Google Scholar 

  82. Murphy C., Kanaganayagam GS, Jiang B., et al. Vascular dysfunction and reduced circulating endothelial progenitor cells in young healthy UK South Asian men. Arterioscler Thromb Vasc Biol. 2007;27:936–942.

    Article  CAS  PubMed  Google Scholar 

  83. Lteif AA, Han K., Mather KJ Obesity, insulin resistance, and the metabolic syndrome: determinants of endothelial dysfunction in whites and blacks. Circulation. 2005;112:32–38.

    Article  CAS  PubMed  Google Scholar 

  84. Kalra L., Rambaran C., Chowienczyk P., et al. Ethnic differences in arterial responses and inflammatory markers in Afro-Caribbean and Caucasian subjects. Arterioscler Thromb Vasc Biol. 2005;25:2362–2367.

    Article  CAS  PubMed  Google Scholar 

  85. Kalra L., Rambaran C., Iveson E., et al. The role of inheritance and environment in predisposition to vascular disease in people of African descent. J Am Coll Cardiol. 2006;47: 1126–1133.

    Article  PubMed  Google Scholar 

  86. Houghton JL, Carr AA, Strogatz DS, et al. Coronary vasomotor reactivity among normotensive African and white American subjects with chest pain. Am J Med. 1997;102:245–251.

    Article  CAS  PubMed  Google Scholar 

  87. Houghton JL, Philbin EF, Strogatz DS, et al. The presence of African American race predicts improvement in coronary endothelial function after supplementary L-arginine. J Am Coll Cardiol. 2002;39:1314–1322.

    Article  PubMed  Google Scholar 

  88. Houghton JL, Smith VE, Strogatz DS, Henches NL, Breisblatt WM, Carr AA Effect of African-American race and hypertensive left ventricular hypertrophy on coronary vascular reactivity and endothelial function. Hypertension. 1997;29: 706–714.

    Article  CAS  PubMed  Google Scholar 

  89. Houghton JL, Strogatz DS, Torosoff MT, et al. African Americans with LVH demonstrate depressed sensitivity of the coronary microcirculation to stimulated relaxation. Hypertension. 2003;42:269–276.

    Article  CAS  PubMed  Google Scholar 

  90. Melikian N., Wheatcroft SB, Ogah OS, et al. Asymmetric dimethylarginine and reduced nitric oxide bioavailability in young Black African men. Hypertension. 2007;49:873–877.

    Article  CAS  PubMed  Google Scholar 

  91. Perregaux D., Chaudhuri A., Rao S., et al. Brachial vascular reactivity in blacks. Hypertension. 2000;36:866–871.

    Article  CAS  PubMed  Google Scholar 

  92. Campia U., Choucair WK, Bryant MB, Waclawiw MA, Cardillo C., Panza JA Reduced endothelium-dependent and -independent dilation of conductance arteries in African Americans. J Am Coll Cardiol. 2002;40:754–760.

    Article  CAS  PubMed  Google Scholar 

  93. Wu HD, Berglund L., Dimayuga C., et al. High lipoprotein(a) levels and small apolipoprotein(a) sizes are associated with endothelial dysfunction in a multiethnic cohort. J Am Coll Cardiol. 2004;43:1828–1833.

    Article  CAS  PubMed  Google Scholar 

  94. Marchesi S., Lupattelli G., Sensini A., et al. Racial difference in endothelial function: role of the infective burden. Atherosclerosis. 2007;191:227–234.

    Article  CAS  PubMed  Google Scholar 

  95. Loehr LR, Espeland MA, Sutton-Tyrrell K., Burke GL, Crouse JR III, Herrington DM Racial differences in endothelial function in postmenopausal women. Am Heart J. 2004;148:606–611.

    Article  CAS  PubMed  Google Scholar 

  96. Gokce N., Holbrook M., Duffy SJ, et al. Effects of race and hypertension on flow-mediated and nitroglycerin-mediated dilation of the brachial artery. Hypertension. 2001;38:1349–1354.

    Article  CAS  PubMed  Google Scholar 

  97. Jawa A., Nachimuthu S., Pendergrass M., Asnani S., Fonseca V. Impaired vascular reactivity in African-American patients with type 2 diabetes mellitus and microalbuminuria or proteinuria despite angiotensin-converting enzyme inhibitor therapy. J Clin Endocrinol Metab. 2006;91:31–35.

    Article  CAS  PubMed  Google Scholar 

  98. Raji A., Gerhard-Herman MD, Warren M., et al. Insulin resistance and vascular dysfunction in nondiabetic Asian Indians. J Clin Endocrinol Metab. 2004;89:3965–3972.

    Article  CAS  PubMed  Google Scholar 

  99. Chambers JC, McGregor A., Jean-Marie J., Kooner JS Abnormalities of vascular endothelial function may contribute to increased coronary heart disease risk in UK Indian Asians. Heart. 1999;81:501–504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Lieberman EH, Gerhard MD, Uehata A., et al. Flow-induced vasodilation of the human brachial artery is impaired in patients 40 years of age with coronary artery disease. Am J Cardiol. 1996;78:1210–1214.

    Article  CAS  PubMed  Google Scholar 

  101. 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.

    Article  CAS  PubMed  Google Scholar 

  102. Sharma A., Basu S., Padginton C., Sung BH, Wilson MF, Dandona P. Absence of Insulin-Mediated Vasodilation in African Americans. Paper presented at: 10th International Congress of Endocrinology; 1996; San Francisco, CA.

  103. Taylor AL, Ziesche S., Yancy C., et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med. 2004;351:2049–2057.

    Article  CAS  PubMed  Google Scholar 

  104. Wallace TW, Drazner MH The impact of race on response to RAAS inhibition. Curr Heart Fail Rep. 2005;2:72–77.

    Article  CAS  PubMed  Google Scholar 

  105. Exner DV, Dries DL, Domanski MJ, Cohn JN Lesser response to angiotensin-converting-enzyme inhibitor therapy in black as compared with white patients with left ventricular dysfunction. N Engl J Med. 2001;344:1351–1357.

    Article  CAS  PubMed  Google Scholar 

  106. Ke RW, Todd Pace D, Ahokas RA. Effect of short-term hormone therapy on oxidative stress and endothelial function in African American and Caucasian postmenopausal women. Fertil Steril. 2003;79:1118–1122.

    Article  PubMed  Google Scholar 

  107. Fenster CP, Darley-Usmar VM, Landar AL, et al.Weight loss and race modulate nitric oxide metabolism in overweight women. Free Radic Biol Med. 2004;37:695–702.

    Article  CAS  PubMed  Google Scholar 

  108. Earle KA, Mehrotra S., Dalton RN, Denver E., Swaminathan R. Defective nitric oxide production and functional renal reserve in patients with type 2 diabetes who have microalbuminuria of African and Asian compared with white origin. J Am Soc Nephrol. 2001;12:2125–2130.

    CAS  PubMed  Google Scholar 

  109. Jackson RW, Treiber FA, Harshfield GA, Waller JL, Pollock JS, Pollock DM Urinary excretion of vasoactive factors are correlated to sodium excretion. Am J Hypertens. 2001;14:1003–1006.

    Article  CAS  PubMed  Google Scholar 

  110. Malhotra S., Poole J., Davis H., et al. Effects of NOS3 Glu298Asp polymorphism on hemodynamic reactivity to stress: influences of ethnicity and obesity. Hypertension. 2004;44:866–871.

    Article  CAS  PubMed  Google Scholar 

  111. Cicinelli E., Ignarro LJ, Matteo MG, Galantino P., Schonauer LM, Falco N. Effects of estrogen replacement therapy on plasma levels of nitric oxide in postmenopausal women. Am J Obstet Gynecol. 1999;180:334–339.

    Article  CAS  PubMed  Google Scholar 

  112. Kalinowski L., Dobrucki IT, Malinski T. Race-specific differences in endothelial function: predisposition of African Americans to vascular diseases. Circulation. 2004;109: 2511–2517.

    Article  PubMed  Google Scholar 

  113. Mason RP, Kalinowski L., Jacob RF, Jacoby AM, Malinski T. Nebivolol reduces nitroxidative stress and restores nitric oxide bioavailability in endothelium of black Americans. Circulation. 2005;112:3795–3801.

    Article  CAS  PubMed  Google Scholar 

  114. Zhou L., Xiang W., Potts J., et al. Reduction in extracellular superoxide dismutase activity in African-American patients with hypertension. Free Radic Biol Med. 2006;41:1384–1391.

    Article  CAS  PubMed  Google Scholar 

  115. Su YR, Rutkowski MP, Klanke CA, et al. A novel variant of the beta-subunit of the amiloride-sensitive sodium channel in African Americans. J Am Soc Nephrol. 1996;7:2543–2549.

    CAS  PubMed  Google Scholar 

  116. Xie HG, Kim RB, Wood AJ, Stein CM Molecular basis of ethnic differences in drug disposition and response. Annu Rev Pharmacol Toxicol. 2001;41:815–850.

    Article  CAS  PubMed  Google Scholar 

  117. Visvikis-Siest S., Marteau JB Genetic variants predisposing to cardiovascular disease. Curr Opin Lipidol. 2006;17:139–151.

    Article  CAS  PubMed  Google Scholar 

  118. Sandrim VC, Coelho EB, Nobre F., Arado GM, Lanchote VL, Tanus-Santos JE Susceptible and protective eNOS haplotypes in hypertensive black and white subjects. Atherosclerosis. 2006; 186:428–432.

    Article  CAS  PubMed  Google Scholar 

  119. Zhu H., Wang X., Dong Y., Treiber FA, Snieder H. Influence of the eNOS gene on development of blood pressure and left ventricular mass: longitudinal findings in multiethnic youth. Pharmacogenet Genomics. 2005;15:669–675.

    CAS  Google Scholar 

  120. Soma M., Nakayama T., Kanmatsuse K. Nitric oxide synthase gene polymorphism and its influence on cardiovascular disease. Curr Opin Nephrol Hypertens. 1999;8:83–87.

    Article  CAS  PubMed  Google Scholar 

  121. Sandrim VC, Yugar-Toledo JC, Desta Z., Flockhart DA, Moreno H Jr, Tanus-Santos JE Endothelial nitric oxide synthase haplotypes are related to blood pressure elevation but not to resistance to antihypertensive drug therapy. J Hypertens. 2006;24:2393–2397.

    Article  CAS  PubMed  Google Scholar 

  122. Tsukada T., Yokoyama K., Arai T., et al. Evidence of association of the ecNOS gene polymorphism with plasma NO metabolite levels in humans. Biochem Biophys Res Commun. 1998;245:190–193.

    Article  CAS  PubMed  Google Scholar 

  123. Hoffmann IS, Tavares-Mordwinkin R., Castejon AM, Alfieri AB, Cubeddu LX Endothelial nitric oxide synthase polymorphism, nitric oxide production, salt sensitivity and cardiovascular risk factors in Hispanics. J Hum Hypertens. 2005;19:233–240.

    Article  CAS  PubMed  Google Scholar 

  124. Uwabo J., Soma M., Nakayama T., Kanmatsuse K. Association of a variable number of tandem repeats in the endothelial constitutive nitric oxide synthase gene with essential hypertension in Japanese. Am J Hypertens. 1998;11:125–128.

    Article  CAS  PubMed  Google Scholar 

  125. Pulkkinen A., Viitanen L., Kareinen A., Lehto S., Vauhkonen I., Laakso M. Intron 4 polymorphism of the endothelial nitric oxide synthase gene is associated with elevated blood pressure in type 2 diabetic patients with coronary heart disease. J Mol Med. 2000;78:372–379.

    Article  CAS  PubMed  Google Scholar 

  126. Nagassaki S., Metzger IF, Souza-Costa DC, Marroni AS, Uzuelli JA, Tanus-Santos JE eNOS genotype is without effect on circulating nitrite/nitrate level in healthy male population. Thromb Res. 2005;115:375–379.

    Article  CAS  PubMed  Google Scholar 

  127. Hwang JJ, Tsai CT, Yeh HM, et al. The 27-bp tandem repeat polymorphism in intron 4 of the endothelial nitric oxide synthase gene is not associated with coronary artery disease in a hospital-based Taiwanese population. Cardiology. 2002;97:67–72.

    Article  CAS  PubMed  Google Scholar 

  128. Zintzaras E., Kitsios G., Stefanidis I. Endothelial NO synthase gene polymorphisms and hypertension: a meta-analysis. Hypertension. 2006;48:700–710.

    Article  CAS  PubMed  Google Scholar 

  129. Casas JP, Cavalleri GL, Bautista LE, Smeeth L., Humphries SE, Hingorani AD Endothelial nitric oxide synthase gene polymorphisms and cardiovascular disease: a HuGE review. Am J Epidemiol. 2006;164:921–935.

    Article  PubMed  Google Scholar 

  130. Marroni AS, Metzger IF, Souza-Costa DC, et al. Consistent interethnic differences in the distribution of clinically relevant endothelial nitric oxide synthase genetic polymorphisms. Nitric Oxide. 2005;12:177–182.

    Article  CAS  PubMed  Google Scholar 

  131. Tanus-Santos JE, Desai M., Flockhart DA Effects of ethnicity on the distribution of clinically relevant endothelial nitric oxide variants. Pharmacogenetics. 2001;11:719–725.

    Article  CAS  PubMed  Google Scholar 

  132. Li R., Lyn D., Lapu-Bula R., et al. Relation of endothelial nitric oxide synthase gene to plasma nitric oxide level, endothelial function, and blood pressure in African Americans. Am J Hypertens. 2004;17:560–567.

    Article  CAS  PubMed  Google Scholar 

  133. Galvin VB, Barakat H., Kemeny G., Macdonald KG, Pories WJ, Hickner RC Endothelial nitric oxide synthase content in adipose tissue from obese and lean African American and white American women. Metabolism. 2005;54:1368–1373.

    Article  CAS  PubMed  Google Scholar 

  134. Leopold JA, Zhang YY, Scribner AW, Stanton RC, Loscalzo J. Glucose-6-phosphate dehydrogenase overexpression decreases endothelial cell oxidant stress and increases bioavailable nitric oxide. Arterioscler Thromb Vasc Biol. 2003;23:411–417.

    Article  CAS  PubMed  Google Scholar 

  135. Hubel CA Oxidative stress in the pathogenesis of preeclampsia. Proc Soc Exp Biol Med. 1999;222:222–235.

    Article  CAS  PubMed  Google Scholar 

  136. Magness RR Maternal cardiovascular and other physiologic responses to the endocrinology of pregnancy. In: Bazer FW, ed. The Endocrinology of Pregnancy. Totowa, NJ: Human Press; 1999:507–539.

    Google Scholar 

  137. Sladek SM, Magness RR, Conrad KP Nitric oxide and pregnancy. Am J Physiol. 1997;272:R441–R463.

    CAS  PubMed  Google Scholar 

  138. Yallampalli C., Garfield RE Inhibition of nitric oxide synthesis in rats during pregnancy produces signs similar to those of preeclampsia. Am J Obstet Gynecol. 1993;169:1316–1320.

    Article  CAS  PubMed  Google Scholar 

  139. Pettersson A., Hedner T., Milsom I. Increased circulating concentrations of asymmetric dimethyl arginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, in preeclampsia. Acta Obstet Gynecol Scand. 1998;77:808–813.

    Article  CAS  PubMed  Google Scholar 

  140. Holden DP, Fickling SA, Whitley GS, Nussey SS Plasma concentrations of asymmetric dimethylarginine, a natural inhibitor of nitric oxide synthase, in normal pregnancy and preeclampsia. Am J Obstet Gynecol. 1998;178:551–556.

    Article  CAS  PubMed  Google Scholar 

  141. Rytlewski K., Olszanecki R., Korbut R., Zdebski Z. Effects of prolonged oral supplementation with l-arginine on blood pressure and nitric oxide synthesis in preeclampsia. Eur J Clin Invest. 2005;35:32–37.

    Article  CAS  PubMed  Google Scholar 

  142. Guendelman S., Thornton D., Gould J., Hosang N. Obstetric complications during labor and delivery: assessing ethnic differences in California. Womens Health Issues. 2006;16:189–197.

    Article  PubMed  Google Scholar 

  143. Tucker MJ, Berg CJ, Callaghan WM, Hsia J. The Black-White disparity in pregnancy-related mortality from 5 conditions: differences in prevalence and case-fatality rates. Am J Public Health. 2007;97:247–251.

    Article  PubMed  PubMed Central  Google Scholar 

  144. Bryant AS, Seely EW, Cohen A., Lieberman E. Patterns of pregnancy-related hypertension in black and white women. Hypertens Pregnancy. 2005;24:281–290.

    Article  PubMed  Google Scholar 

  145. Tanaka M., Jaamaa G., Kaiser M., et al. Racial disparity in hypertensive disorders of pregnancy in New York State: a 10-year longitudinal population-based study. Am J Public Health. 2007;97:163–170.

    Article  PubMed  PubMed Central  Google Scholar 

  146. Shen JJ, Tymkow C., MacMullen N. Disparities in maternal outcomes among four ethnic populations. Ethn Dis. 2005; 15:492–497.

    PubMed  Google Scholar 

  147. Van Buren GA, Yang DS, Clark KE Estrogen-induced uterine vasodilatation is antagonized by L-nitroarginine methyl ester, an inhibitor of nitric oxide synthesis. Am J Obstet Gynecol. 1992;167:828–833.

    Article  PubMed  Google Scholar 

  148. Williams DJ, Vallance PJ, Neild GH, Spencer JA, Imms FJ Nitric oxide-mediated vasodilation in human pregnancy. Am J Physiol. 1997;272:H748–H752.

    CAS  PubMed  Google Scholar 

  149. Miller SL, Jenkin G., Walker DW Effect of nitric oxide synthase inhibition on the uterine vasculature of the late-pregnant ewe. Am J Obstet Gynecol. 1999;180: 1138–1145.

    Article  CAS  PubMed  Google Scholar 

  150. Rosenfeld CR, Cox BE, Roy T., Magness RR Nitric oxide contributes to estrogen-induced vasodilation of the ovine uterine circulation. J Clin Invest. 1996;98:2158–2166.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Buhimschi I., Ali M., Jain V., Chwalisz K., Garfield RE Differential regulation of nitric oxide in the rat uterus and cervix during pregnancy and labour. Hum Reprod. 1996;11:1755–1766.

    Article  CAS  PubMed  Google Scholar 

  152. Sladek SM, Regenstein AC, Lykins D., Roberts JM Nitric oxide synthase activity in pregnant rabbit uterus decreases on the last day of pregnancy. Am J Obstet Gynecol. 1993; 169:1285–1291.

    Article  CAS  PubMed  Google Scholar 

  153. Gibson CS, MacLennan AH, Dekker GA, et al. Genetic polymorphisms and spontaneous preterm birth. Obstet Gynecol. 2007;109:384–391.

    Article  CAS  PubMed  Google Scholar 

  154. Lade JA, Moses EK, Guo G., et al.The eNOS gene: a candidate for the preeclampsia susceptibility locus? Hypertens Pregnancy. 1999;18:81–93.

    Article  CAS  PubMed  Google Scholar 

  155. Vita JA Nitric oxide-dependent vasodilation in human subjects. Methods Enzymol. 2002;359:186–200.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Reproductive Medicine, University of California, San Diego, USA

    Eugenia Mata-Greenwood PhD, PharmD & Dong-Bao Chen PhD

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  1. Eugenia Mata-Greenwood PhD, PharmD
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  2. Dong-Bao Chen PhD
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Correspondence to Eugenia Mata-Greenwood PhD, PharmD.

Additional information

The present study was supported in part by the American Heart Association Scientist development grant 0630297N (to EM-G) and the National Institutes of Health RO1 grants HL 70562 and HL74947 (to D-BC).

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Mata-Greenwood, E., Chen, DB. Racial Differences in Nitric Oxide—Dependent Vasorelaxation. Reprod. Sci. 15, 9–25 (2008). https://doi.org/10.1177/1933719107312160

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