Published online before print May 24, 2004, doi: 10.1161/01.CIR.0000129087.81352.7A
(Circulation. 2004;109:2511-2517.)
© 2004 American Heart Association, Inc.
Clinical Investigation and Reports |
Race-Specific Differences in Endothelial Function
Predisposition of African Americans to Vascular Diseases
From the Department of Biochemistry, Ohio University, Athens. Dr Kalinowski was on sabbatical leave from the Department of Clinical Biochemistry, Medical University of Gdansk, and Laboratory of Cellualr and Molecular Nephrology of the Polish Academy of Science, Poland.
Correspondence to Tadeusz Malinski, Department of Biochemistry, Ohio University, Athens, OH 45701. E-mail malinski{at}ohiou.edu
Received October 13, 2003; denovo received December 12, 2003; accepted February 17, 2004.
Background— The prevalence of the endothelium-impaired function disorders, such as hypertension and diabetes mellitus, and the severity of their complications are considerably greater in blacks than whites. Evidence has accumulated that superoxide (O2–) production and its interaction with nitric oxide (NO), yielding the strong oxidant peroxynitrite (ONOO–), play central roles in vascular pathophysiology. We hypothesized that the differences in endothelial NO/O2–/ONOO– metabolism may highlight the potential predisposition to endothelial dysfunction and cardiovascular complications prevalent in blacks.
Methods and Results— Highly sensitive tandem electrochemical NO/O2–/ONOO– nanosensors were positioned in single human umbilical vein endothelial cells (HUVECs) isolated from blacks and whites, and the kinetics of NO/O2–/ONOO– release were recorded in vitro. HUVECs were also analyzed by Western immunoblotting and enzyme activity assays for NAD(P)H-oxidase and endothelial NO synthase (eNOS). Compared with whites, HUVECs from blacks elicited reduced release of bioactive NO with an accompanying increase in the release of both O2– and ONOO–. The greater potency of NO production because of eNOS upregulation in HUVECs from blacks is associated with a decrease in the NO bioavailability. This is due to increased NO degradation by excess O2– produced primarily by 2 enzymatic sources: NAD(P)H-oxidase and uncoupled eNOS.
Conclusions— Compared with whites, the steady-state NO/O2–/ONOO– balance in endothelial cells from blacks is kept closer to the redox states characteristic for the endothelium-impaired function disorders. This may explain the differences in racial predisposition to the endothelium dysfunction during ongoing vascular disturbances with the hallmark of enhanced NO inactivation within the endothelium by oxidative stress.
Key Words: nitric oxide • endothelium • risk factors • African Americans • ethnic groups
This article has been cited by other articles:
 |
|
 |
|
  L. L. Nguyen, N. Hevelone, S. O. Rogers, D. F. Bandyk, A. W. Clowes, G. L. Moneta, S. Lipsitz, and M. S. Conte Disparity in Outcomes of Surgical Revascularization for Limb Salvage: Race and Gender Are Synergistic Determinants of Vein Graft Failure and Limb Loss Circulation, January 6, 2009; 119(1): 123 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Y. Lee, R. J. Prineas, and J. W. Eaton Heritability of Erythrocyte Sodium Permeability: A Possible Genetic Marker for Hypertension Ann. Clin. Lab. Sci., January 1, 2009; 39(3): 241 - 250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Gordon and B. A. Teachman Ethnic Group Differences in Affective, Behavioral, and Cognitive Markers of Anxiety Journal of Cross-Cultural Psychology, July 1, 2008; 39(4): 424 - 446. [Abstract] [PDF]
|
|
|
|
 |
|
 E. Mata-Greenwood and D.-B. Chen Racial Differences in Nitric Oxide--Dependent Vasorelaxation Reproductive Sciences, January 1, 2008; 15(1): 9 - 25. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Lavi, E. H. Yang, A. Prasad, V. Mathew, G. W. Barsness, C. S. Rihal, L. O. Lerman, and A. Lerman The Interaction Between Coronary Endothelial Dysfunction, Local Oxidative Stress, and Endogenous Nitric Oxide in Humans Hypertension, January 1, 2008; 51(1): 127 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Waikar, G. C. Curhan, J. Z. Ayanian, and G. M. Chertow Race and Mortality after Acute Renal Failure J. Am. Soc. Nephrol., October 1, 2007; 18(10): 2740 - 2748. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. O. Pierce Jr Ethnic and Racial Disparities in Diagnosis, Treatment, and Follow-up Care J. Am. Acad. Ortho. Surg., September 1, 2007; 15(suppl_1): S8 - S12. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Bibbins-Domingo and A. Fernandez BiDil for Heart Failure in Black Patients: Implications of the U.S. Food and Drug Administration Approval Ann Intern Med, January 2, 2007; 146(1): 52 - 56. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Ge, H. Zhu, Y. Huang, F. A. Treiber, G. A. Harshfield, H. Snieder, and Y. Dong Multilocus Analyses of Renin-Angiotensin-Aldosterone System Gene Variants on Blood Pressure at Rest and During Behavioral Stress in Young Normotensive Subjects Hypertension, January 1, 2007; 49(1): 107 - 112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Brewster, G. Mairuhu, N. R. Bindraban, R. P. Koopmans, J. F. Clark, and G. A. van Montfrans Creatine Kinase Activity Is Associated With Blood Pressure Circulation, November 7, 2006; 114(19): 2034 - 2039. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. I. Brandt-Rauf, V. H. Raveis, N. F. Drummond, J. A. Conte, and S. M. Rothman Ashkenazi Jews and Breast Cancer: The Consequences of Linking Ethnic Identity to Genetic Disease Am J Public Health, November 1, 2006; 96(11): 1979 - 1988. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Lillquist and C. A. Sullivan Legal Regulation of the Use of Race in Medical Research J. Law Med. Ethics, September 1, 2006; 34(3): 535 - 551. [PDF]
|
|
|
|
 |
|
 S. B. Haga and G. S. Ginsburg Prescribing BiDil: Is It Black and White? J. Am. Coll. Cardiol., July 4, 2006; 48(1): 12 - 14. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Angus, W. T. Linde-Zwirble, S. W. Tam, J. K. Ghali, M. L. Sabolinski, V. G. Villagra, W. C. Winkelmayer, M. Worcel, and for the African-American Heart Failure Trial (A-He Cost-Effectiveness of Fixed-Dose Combination of Isosorbide Dinitrate and Hydralazine Therapy for Blacks With Heart Failure Circulation, December 13, 2005; 112(24): 3745 - 3753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Mason, L. Kalinowski, R. F. Jacob, A. M. Jacoby, and T. Malinski Nebivolol Reduces Nitroxidative Stress and Restores Nitric Oxide Bioavailability in Endothelium of Black Americans Circulation, December 13, 2005; 112(24): 3795 - 3801. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Barr The Practitioner's Dilemma: Can We Use a Patient's Race To Predict Genetics, Ancestry, and the Expected Outcomes of Treatment? Ann Intern Med, December 6, 2005; 143(11): 809 - 815. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Brzezinska, N. Lohr, and W. M. Chilian Electrophysiological effects of O2-{middle dot} on the plasma membrane in vascular endothelial cells Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2379 - H2386. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Dani, G. Bertini, F. F. Rubaltelli, S. U. Hasan, E. C. Lasser, K. Van Meurs, D. Stevenson, M. D. Schreiber, J. D. Marks, K. K.L. Mestan, et al. Inhaled nitric oxide. N. Engl. J. Med., October 13, 2005; 353(15): 1626 - 1628. [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Sackner, E. Gummels, and J. A. Adams Effect of Moderate-Intensity Exercise, Whole-Body Periodic Acceleration, and Passive Cycling on Nitric Oxide Release Into Circulation Chest, October 1, 2005; 128(4): 2794 - 2803. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Zitouni, J. Nourooz-Zadeh, D. Harry, S. M. Kerry, D. J. Betteridge, F. P. Cappuccio, and K. A. Earle Race-Specific Differences in Antioxidant Enzyme Activity in Patients With Type 2 Diabetes: A potential association with the risk of developing nephropathy Diabetes Care, July 1, 2005; 28(7): 1698 - 1703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. W. Yancy, E. J. Benjamin, R. P. Fabunmi, and R. O. Bonow Discovering the Full Spectrum of Cardiovascular Disease: Minority Health Summit 2003: Executive Summary Circulation, March 15, 2005; 111(10): 1339 - 1349. [Full Text] [PDF]
|
|
|
|
|
|
A. L. Taylor, S. Ziesche, C. Yancy, P. Carson, R. D'Agostino Jr., K. Ferdinand, M. Taylor, K. Adams, M. Sabolinski, M. Worcel, et al. Combination of Isosorbide Dinitrate and Hydralazine in Blacks with Heart Failure N. Engl. J. Med., November 11, 2004; 351(20): 2049 - 2057. [Abstract] [Full Text] [PDF]
|
|