New insights into the renin-angiotensin system and hypertensive renal disease.

The role of the renin-angiotensin system in hypertension and end organ damage has long been recognized. Recent advances in genetic models and newly available pharmacologic tools have allowed dissection of the mechanisms of actions of the renin-angiotensin system in hypertensive kidney disease. The newly cloned AT(2) receptor is now recognized to oppose many of the AT(1) receptor"s actions. The renin-angiotensin system is now recognized to be linked to induction of plasminogen activator inhibitor-1 (PAI-1), possibly via the AT(4) receptor, thus promoting both thrombosis and fibrosis. Interactions of the renin-angiotensin system with aldosterone and bradykinin may have impact on both blood pressure and tissue injury. The effects of angiotensin 1 converting enzyme inhibitors versus those of the newly available AT(1) receptor antagonists on blood pressure and organ damage are undergoing evaluation in clinical trials. Finally, polymorphisms of genes relevant to the renin-angiotensin system appear to affect response to treatment, although this effect varies in different populations.