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

Abstract

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 phox (gp91 phox−/− ) 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 β-myosin heavy chain mRNA expression, myocyte area, and cardiac collagen content in wild-type but not gp91 phox−/− mice. Angiotensin II treatment increased myocardial NADPH oxidase activity in wild-type but not gp91 phox−/− mice. Conclusions — A gp91 phox -containing NADPH oxidase plays an important role in the development of angiotensin II-induced cardiac hypertrophy, independent of changes in blood pressure.