Pressure Overload–Induced Myocardial Hypertrophy in Mice Does Not Require gp91

Background—Reactive oxygen species (ROS) may mediate pressure overload–induced myocardial hypertrophy. NADPH oxidase may be involved in this process, because its expression and activity are upregulated by pressure overload and because myocardial hypertrophy caused by a subpressor infusion of angiotensin is attenuated in mice deficient in the gp91 catalytic subunit of NADPH oxidase. Methods and Results—To test the role of NADPH oxidase–dependent ROS in mediating pressure overload–induced myocardial hypertrophy, we subjected transgenic mice lacking gp91 to chronic pressure overload caused by constriction of the ascending aorta. Contrary to our hypothesis, neither myocardial hypertrophy nor NADPH-dependent superoxide generation was decreased in gp91-deficient mice after aortic constriction. Aortic constriction caused an exaggerated increase in p22 and p47 mRNA in gp91-deficient mice. Conclusions—These results indicate that gp91 is not necessary for pressure overload–induced hypertrophy in the mouse and suggest the involvement of another source of ROS, possibly an NADPH oxidase that does not require the gp91 subunit. (Circulation. 2004;109:1168-1171.)