Sex differences in protection against angiotensin II-induced endothelial dysfunction by manganese superoxide dismutase in the cerebral circulation.
Angiotensin II (Ang II) produces oxidative stress and endothelial dysfunction in blood vessels. The vasculature from females may be protected against deleterious effects of Ang II. We tested the hypothesis that manganese superoxide dismutase (MnSOD) protects against Ang II-induced endothelial dysfunction. Experiments were performed in C57Bl/6, wild-type (MnSOD(+/+)), and MnSOD-deficient (MnSOD(+/-)) mice treated systemically with vehicle or Ang II. Basilar arteries were isolated from mice treated for 1 week with a nonpressor dose of Ang II (0.28 mg/kg per day). Ang II treatment produced superoxide-mediated impairment of responses to the endothelium-dependent vasodilator acetylcholine (P<0.05). In male but not female MnSOD(+/+) mice, Ang II modestly inhibited responses to acetylcholine (P<0.05). In contrast, Ang II selectively impaired these responses by up to 70% in male MnSOD(+/-) mice (P<0.05), and this effect was reversed by Tempol (P<0.05). Ang II had no effect on acetylcholine responses in MnSOD(+/-) female mice. Vascular superoxide levels after treatment with an inhibitor of CuZn and extracellular superoxide dismutase were higher in Ang II-treated versus vehicle-treated MnSOD(+/-) mice. Thus, a nonpressor dose of Ang II produces endothelial dysfunction in male mice only, suggesting that the female vasculature is protected from Ang II. In male but not female mice, MnSOD deficiency enhanced endothelial dysfunction, suggesting that MnSOD normally protects the vasculature during disease states in which Ang II contributes to vascular dysfunction.
Chrissobolis
Sophocles
S
Department of Internal Medicine, Cardiovascular Center, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242-1081, USA.
Faraci
Frank M
FM
D000109:Acetylcholine / Q000494:pharmacology; D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009599:Nitroprusside / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012727:Sex Characteristics; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology
D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; D000804:Angiotensin II; D009599:Nitroprusside; D013482:Superoxide Dismutase; D000109:Acetylcholine