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 (O2−) production is involved in the deoxycorticosterone acetate (DOCA)-salt-induced hypertension, using mice which are genetically deficient in gp91phox, 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 O2− 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 O2− production between gp91−/− DOCA-salt-treated and sham mice. These findings suggest that vascular O2− overproduction via gp91phox-containing NADPH oxidase is one of the crucial factors in the development of DOCA-salt-induced hypertension.