Increased cardiac angiotensin II levels induce right and left ventricular hypertrophy in normotensive mice

Angiotensin II is a potent arterial vasoconstrictor and induces hypertensio n. Angiotensin LT also exerts a trophic effect on cardiomyocytes in vitro. The goals of the present study were to document an in vivo increase in card iac angiotensins in the absence of elevated plasma levels or hypertension a nd to investigate prevention or regression of ventricular hypertrophy by re nin-angiotensin system blockade. We demonstrate that high cardiac angiotens in II is directly responsible for right and left ventricular hypertrophy. W e used transgenic mice overexpressing angiotensinogen in cardiomyocytes cha racterized by cardiac hypertrophy without fibrosis and normal blood pressur e. Angiotensin-converting enzyme inhibition and angiotensin II type 1 recep tor blockade prevent or normalize ventricular hypertrophy. Surprisingly, in control mice, receptor blockade decreases tissue angiotensin LI despite in creased plasma levels. This suggests that angiotensin II may be protected f rom metabolization by binding to its receptor. Blocking of the angiotensin ii type 1 receptor rather than enhanced stimulation of the angiotensin II t ype 2 receptor may prevent remodeling and account for the beneficial effect s of angiotensin antagonists.