Contrasting Roles of NADPH Oxidase Isoforms in Pressure-Overload Versus Angiotensin II–Induced Cardiac Hypertrophy

Abstract

Increased production of reactive oxygen species (ROS) is implicated in the development of left ventricular hypertrophy (LVH). Phagocyte-type NADPH oxidases are major cardiovascular sources of ROS, and recent data indicate a pivotal role of a gp91 phox -containing NADPH oxidase in angiotensin II (Ang II)–induced LVH. We investigated the role of this oxidase in pressure-overload LVH. gp91 phox−/− mice and matched controls underwent chronic Ang II infusion or aortic constriction. Ang II–induced increases in NADPH oxidase activity, atrial natriuretic factor (ANF) expression, and cardiac mass were inhibited in gp91 phox−/− mice, whereas aortic constriction-induced increases in cardiac mass and ANF expression were not inhibited. However, aortic constriction increased cardiac NADPH oxidase activity in both gp91 phox−/− and wild-type mice. Myocardial expression of an alternative gp91 phox isoform, Nox4, was upregulated after aortic constriction in gp91 phox−/− mice. The antioxidant, N -acetyl-cysteine, inhibited pressure-overload–induced LVH in both gp91 phox−/− and wild-type mice. These data suggest a differential response of the cardiac Nox isoforms, gp91 phox and Nox4, to Ang II versus pressure overload.