Pivotal Role of a gp91-Containing NADPH Oxidase in Angiotensin II–Induced Cardiac Hypertrophy in Mice

Background—Angiotensin II induces both cardiac and vascular smooth muscle (VSM) hypertrophy. Recent studies suggest a central role for a phagocyte-type NADPH oxidase in angiotensin II–induced VSM hypertrophy. The possible involvement of an NADPH oxidase in the development of cardiac hypertrophy has not been studied. Methods and Results—Mice with targeted disruption of the NADPH oxidase subunit gp91 (gp91 / ) and matched wild-type mice were subjected to subcutaneous angiotensin II infusion at a subpressor dose (0.3 mg/kg/day) for 2 weeks. Systolic blood pressure was unaltered by angiotensin II in either group. Angiotensin II significantly increased heart/body weight ratio, atrial natriuretic factor and -myosin heavy chain mRNA expression, myocyte area, and cardiac collagen content in wild-type but not gp91 / mice. Angiotensin II treatment increased myocardial NADPH oxidase activity in wild-type but not gp91 / mice. Conclusions—A gp91-containing NADPH oxidase plays an important role in the development of angiotensin II–induced cardiac hypertrophy, independent of changes in blood pressure. (Circulation. 2002;105:293-296.)