Contrasting roles of NADPH oxidase isoforms in pressure-overload versus angiotensin II - Induced cardiac hypertrophy

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.