Role of superoxide anion in regulating pressor and vascular hypertrophic response to angiotensin II.
Our purpose was to address the role of NAPDH oxidase-derived superoxide anion in the vascular response to ANG II. Blood pressure, aortic superoxide anion, 3-nitrotyrosine, and medial cross-sectional area were compared in wild-type mice and in mice that overexpress human superoxide dismutase (hSOD). The pressor response to ANG II was significantly less in hSOD mice. Superoxide anion levels were increased twofold in ANG II-treated wild-type mice but not in hSOD mice. 3-Nitrotyrosine increased in aortic endothelium and adventitia in wild-type but not hSOD mice. In contrast, aortic medial cross-sectional area increased 50% with ANG II in hSOD mice, comparable to wild-type mice. The lower pressor response to ANG II in the mice expressing hSOD is consistent with a pressor role of superoxide anion in wild-type mice, most likely because it reacts with nitric oxide. Despite preventing the increase in superoxide anion and 3-nitrotyrosine, the aortic hypertrophic response to ANG II in vivo was unaffected by hSOD.
Wang
Hui Di
HD
Department of Pharmacology and Cardiovascular Risk Factor Reduction Unit, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5E5.
Johns
Douglas G
DG
Xu
Shanqin
S
Cohen
Richard A
RA
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects*; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology*; D015870:Gene Expression; D006801:Humans; D006984:Hypertrophy; D007150:Immunohistochemistry; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis
D013481:Superoxides; D000804:Angiotensin II; C002744:3-nitrotyrosine; D014443:Tyrosine; D013482:Superoxide Dismutase; D019255:NADPH Oxidases