Upregulation of p67(phox) and gp91(phox) in aortas from angiotensin II-infused mice.
Although NAD(P)H oxidase-derived superoxide (O(2)(-)) is increased during the development of angiotensin II (ANG II)-dependent hypertension, vascular regulation at the protein level has not been reported. We have shown that four major components of NAD(P)H oxidase are located primarily in the vascular adventitia as a primary source of vascular O(2)(-). Here we compare vascular levels of O(2)(-) and NAD(P)H oxidase in normotensive and ANG II-infused hypertensive mice and show that, after 7 days of ANG II infusion (750 microg. kg(-1). day(-1) ip) in C57B1/6 mice, systolic blood pressure was increased compared with that after sham infusion, concomitant with increased O(2)(-) in the thoracic aorta as measured using lucigenin (25 microM)-enhanced chemiluminescence. Both p67(phox) and gp91(phox) were detectable by Western blotting in aortic homogenates, and we observed increased protein levels of NAD(P)H oxidase subunits. These ANG II-induced increases were normalized by simultaneous treatment with the AT(1) receptor antagonist losartan. Moreover, the primary location of these subunits was the adventitia as detected immunohistochemically. Our results suggest that ANG II-induced increases in O(2)(-) are due to increased adventitial NAD(P)H oxidase activity, brought about by the heightened expression and interaction of its components.
Cifuentes
M E
ME
Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Michigan 48202-2689, USA.
Rey
F E
FE
Carretero
O A
OA
Pagano
P J
PJ
D000804:Angiotensin II / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D066298:In Vitro Techniques; D007263:Infusions, Parenteral; D019808:Losartan / Q000494:pharmacology; D008163:Luminescent Measurements; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D009928:Organ Specificity / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000959:Antihypertensive Agents; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; C079789:neutrophil cytosol factor 67K; D013481:Superoxides; D000804:Angiotensin II; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D019808:Losartan