Role of angiotensin AT1 and AT2 receptors in cardiac hypertrophy and disease

Angiotensin II modulates beat-to-beat cardiac performance as a potent vasocontrictor, inotrope, and regulator of water and electrolyte balance. It is also a growth factor that can stimulate the early molecular growth responses of proto-oncogene activation and new protein synthesis, and the later event of cardiocyte hypertrophy independent from load. Its effects are mediated through the angiotensin II type 1 (AT1) receptor, which exists as the AT1a and AT1b isoforms, and the angiotensin II type 2 (AT2) receptor. There is still controversy regarding the role of activation of the AT1 receptor subtype(s) as a mandatory signal versus modulatory regulator of the transduction of mechanical load in pressure-overload hypertrophy due to hypertension or aortic stenosis. The role of the AT2 receptor subtype in the heart is even less well understood, although this receptor appears to serve as an antigrowth signal in proliferating cells. Here we review current data on these controversies, including new data that support the notion that angiotensin II activation of the cardiac AT2 receptor subtype inhibits the effects of angiotensin II on the immediate growth response in the adult heart.