Role of angiotensin AT(1) and AT(2) receptors in cardiac hypertrophy and disease

Angiotensin II modulates beat-to-beat cardiac performance as a potent vasoc ontrictor, inotrope, and regulator of water and electrolyte balance. It is also a growth factor that can stimulate the early molecular growth response s of proto-oncogene activation and new protein synthesis, and the later eve nt of cardiocyte hypertrophy independent from load. Its effects are mediate d through the angiotensin II type 1 (AT(1)) receptor, which exists as the A T(1a) and AT(1b) isoforms, and the angiotensin II type 2 (AT(2)) receptor. There is still controversy regarding the role of activation of the AT(1) re ceptor subtype(s) as a mandatory signal versus modulatory regulator of the transduction of mechanical load in pressure-overload hypertrophy due to hyp ertension or aortic stenosis. The role of the AT(2) receptor subtype in the heart is even less well understood, although this receptor appears to serv e as an antigrowth signal in proliferating cells. Here we review current da ta on these controversies, including new data that support the notion that angiotensin II activation of the cardiac AT(2) receptor subtype inhibits th e effects of angiotensin II on the immediate growth response in the adult h eart. (C)1999 by Excerpta Medica, Inc.