title: Race-specific differences in endothelial function: predisposition of African Americans to vascular diseases.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Biochemistry, Ohio University, Athens, OH 45701, USA.
authors.forename: Leszek
authors.initials: L
authors.lastname: Kalinowski
authors.forename: Iwona T
authors.initials: IT
authors.lastname: Dobrucki
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Malinski
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000328:Adult; D001741:Black or African American; D001578:Benzopyrans / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D004198:Disease Susceptibility; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D005260:Female; D006801:Humans; D008469:Meclofenamic Acid / Q000494:pharmacology; D009243:NAD / Q000494:pharmacology; D009249:NADP / Q000494:pharmacology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D036103:Nanotechnology / Q000295:instrumentation; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010117:Oxypurinol / Q000494:pharmacology; D030421:Peroxynitrous Acid / Q000378:metabolism; D010750:Phosphoproteins / Q000032:analysis; D012402:Rotenone / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D014652:Vascular Diseases / Q000201:enzymology / Q000208:ethnology* / Q000503:physiopathology; D044465:White People
chemical_list: C438505:6,8-diallyl 5,7-dihydroxy 2-(2-allyl 3-hydroxy 4-methoxyphenyl)1-H benzo(b)pyran-4-one; D000098:Acetophenones; D001578:Benzopyrans; D010750:Phosphoproteins; C079789:neutrophil cytosol factor 67K; D012402:Rotenone; D009243:NAD; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D008469:Meclofenamic Acid; D009249:NADP; C056165:acetovanillone; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D010117:Oxypurinol