Circulation Research. 2001;88:947-953
Published online before print April 27, 2001, doi: 10.1161/hh0901.089987
Published online before print April 27, 2001, doi: 10.1161/hh0901.089987
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© 2001 American Heart Association, Inc.
Integrative Physiology |
Role of NADPH Oxidase in the Vascular Hypertrophic and Oxidative Stress Response to Angiotensin II in Mice
From the Vascular Biology Unit (H.D.W., S.X., D.G.J., Y.D., A.J.C., R.A.C.), Whitaker Cardiovascular Institute, Department of Medicine, Boston University Medical Center, Boston, Mass, and Department of Veterinary Biology (M.T.Q.), Montana State University, Bozeman, Mont.
Correspondence to Richard A. Cohen, MD, Vascular Biology Unit, X708, Boston University School of Medicine, 650 Albany St, Boston, MA 02118. E-mail racohen{at}medicine.bu.edu
Abstract—Oxygen-derived free radicals are involved in the vascular response to angiotensin II (Ang II), but the role of NADPH oxidase, its subunit proteins, and their vascular localization remain controversial. Our purpose was to address the role of NADPH oxidase in the blood pressure (BP), aortic hypertrophic, and oxidant responses to Ang II by taking advantage of knockout (KO) mice that are genetically deficient in gp91phox, an NADPH oxidase subunit protein. The baseline BP was significantly lower in KO mice than in wild-type (WT) (92±2 [KO] versus 101±1 [WT] mm Hg, P<0.01), but infusion of Ang II for 6 days caused similar increases in BP in the 2 strains (33±4 [KO] versus 38±2 [WT] mm Hg, P>0.4). Ang II increased aortic superoxide anion production 2-fold in the aorta of WT mice but did not do so in KO mice. Aortic medial area increased in WT (0.12±0.02 to 0.17±0.02 mm2, P<0.05), but did not do so in KO mice (0.10±0.01 to 0.11±0.01 mm2, P>0.05). Histochemistry and polymerase chain reaction demonstrated gp91phox localized in endothelium and adventitia of WT mice. Levels of reactive oxidant species as indicated by 3-nitrotyrosine immunoreactivity increased in these regions in WT but not in KO mouse aorta in response to Ang II. These results indicate an essential role in vivo of gp91phox and NADPH oxidase–derived superoxide anion in the regulation of basal BP and a pressure-independent vascular hypertrophic and oxidant stress response to Ang II.
Key Words: angiotensin II • superoxide anion • 3-nitrotyrosine • gp91phox • NADPH oxidase
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