Upregulation of p67 phox and gp91 phox in aortas from angiotensin II-infused mice

• Published in: American journal of physiology. Heart and circulatory physiology 2000-11, Vol.279 (5), p.H2234-H2240
• Main Authors: Cifuentes, M. Eugenia, Rey, Federico E., Carretero, Oscar A., Pagano, Patrick J.
• Format: Article
• Language: English
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.2000.279.5.H2234

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 μg · 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 μM)-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.