Pressure overload-induced myocardial hypertrophy in mice does not require gp91phox.

Abstract

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 gp91phox catalytic subunit of NADPH oxidase. To test the role of NADPH oxidase-dependent ROS in mediating pressure overload-induced myocardial hypertrophy, we subjected transgenic mice lacking gp91phox 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 gp91phox-deficient mice after aortic constriction. Aortic constriction caused an exaggerated increase in p22phox and p47phox mRNA in gp91phox-deficient mice. These results indicate that gp91phox 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 gp91phox subunit.