Role of gp91phox-containing NADPH oxidase in the deoxycorticosterone acetate-salt-induced hypertension

NADPH oxidase plays an important role in vascular oxidative stress in hypertensive diseases. We evaluated whether NADPH oxidase-dependent superoxide (02) production is involved in the deoxycorticosterone acetate (DOCA)-salt-induced hypertension, using mice which are genetically deficient in gp91 phox, an NADPH oxidase subunit protein (gp91(-/-) mice). Two weeks after the DOCA-salt treatment, systolic blood pressure was significantly elevated in wild-type mice, but not in gp91(-/-) mice. After a 5-week treatment period, wild-type mice developed high blood pressure, with a systolic blood pressure of 127 +/- 3 mm Hg, compared with 107 +/- 4 mm Hg in gp91(-/-) mice. Aortic O-2(-) production in wild-type DOCA-salt-treated mice was significantly higher than that in wild-type sham mice, whereas there were no significant differences in aortic 02 production between gp91(-/-) DOCA-salt-treated and sham mice. These findings suggest that vascular O-2(-) overproduction via gp91 phox-containing NADPH oxidase is one of the crucial factors in the development of DOCA-salt-induced hypertension. (c) 2006 Elsevier B.V. All rights reserved.