Theoretical basis and clinical evidence for differential effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor subtype 1 blockers

Drugs that block the renin-angiotensin system have multiple mechanisms of a ction that may be beneficial in stabilizing or delaying progression of rena l disease. The most important of these actions is the simultaneous control of both systemic and glomerular capillary hypertension. Angiotensin-convert ing enzyme (ACE) inhibitors are a class of drugs that have proven antihyper tensive and antiproteinuric effects, with a demonstrated ability to delay p rogression of renal disease in conjunction with the ability to reduce syste mic blood pressure. The mechanism of action for these drugs remains poorly described, but depends in part on an ability to reduce plasma angiotensin I I levels and increase plasma bradykinin levels. Angiotensin II receptor sub type 1 (AT(1)) blockers differ in their mechanism of action from the ACE in hibitors. These drugs primarily block the binding of angiotensin II to its type 1 site. In so blocking the type 1 binding site, however, greater level s of circulating angiotensin II result, and the resultant biologic activity of angiotensin II or its metabolites such as angiotensin((1-7)) and angiot ensin((3-8)) may be more directed to other angiotensin-binding sites. AT(1) blockers have similar antihypertensive and antiproteinuric effects to thos e of ACE inhibitors and they may prove to be as useful as ACE inhibitors in delaying progression of renal disease. Because ACE inhibitors and AT(1) bl ockers inhibit the renin-angiotensin system by different mechanisms, there is a possibility that combining them in clinical practice may prove efficac ious for lowering blood pressure and for providing target organ protection, Curr Opin Nephrol Hypertens 9:403-411. (C) 2000 Lippincott Williams & Wilk ins.