ANGIOTENSIN-II TYPE-1 RECEPTOR-INDUCED SIGNAL-TRANSDUCTION PATHWAYS AS NEW TARGETS FOR PHARMACOLOGICAL TREATMENT OF THE RENIN-ANGIOTENSIN SYSTEM

The peptide hormone angiotensin II is the main effector of the renin a ngiotensin system and may be involved in the pathogenesis of several c ardiovascular diseases such as congestive heart failure and hypertensi on. Drugs developed to inhibit angiotensin II effects such as angioten sin-converting enzyme (ACE) inhibitors or receptor antagonists helped to detect the cardiovascular and cellular mechanisms of angiotensin II effects. ACE inhibitor effects are complex and include indirect as we ll as direct mechanisms. Indirect effects are mediated by unloading th e heart via prevention of aldosterone release and modulation of sympat hetic nervous system activity. Direct actions include the inhibition o f cardiac fibroblast proliferation and collagen synthesis as well as h ypertrophy of cardiomyocytes. Recent work has focused on uncovering th e biochemical and molecular mechanisms of angiotensin II induced cell growth.