Role of NADPH oxidase in the vascular hypertrophic and oxidative stress response to angiotensin II in mice.
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 gp91(phox), 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 mm(2), P<0.05), but did not do so in KO mice (0.10+/-0.01 to 0.11+/-0.01 mm(2), P>0.05). Histochemistry and polymerase chain reaction demonstrated gp91(phox) 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 gp91(phox) 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.
Wang
H D
HD
Vascular Biology Unit, Whitaker Cardiovascular Institute, Department of Medicine, Boston University Medical Center, Boston, Massachusetts, USA.
Xu
S
S
Johns
D G
DG
Du
Y
Y
Quinn
M T
MT
Cayatte
A J
AJ
Cohen
R A
RA
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D005838:Genotype; D006984:Hypertrophy; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000502:physiology*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000187:drug effects / Q000378:metabolism
D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D013481:Superoxides; D000804:Angiotensin II; C002744:3-nitrotyrosine; D014443:Tyrosine; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases