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

Abstract

Drugs that block the renin-angiotensin system have multiple mechanisms of action that may be beneficial in stabilizing or delaying progression of renal disease. The most important of these actions is the simultaneous control of both systemic and glomerular capillary hypertension. Angiotensin-converting enzyme (ACE) inhibitors are a class of drugs that have proven antihypertensive and antiproteinuric effects, with a demonstrated ability to delay progression of renal disease in conjunction with the ability to reduce systemic blood pressure. The mechanism of action for these drugs remains poorly described, but depends in part on an ability to reduce plasma angiotensin II levels and increase plasma bradykinin levels. Angiotensin II receptor subtype 1 (AT1) blockers differ in their mechanism of action from the ACE inhibitors. These drugs primarily block the binding of angiotensin II to its type 1 site. In so blocking the type 1 binding site, however, greater levels of circulating angiotensin II result, and the resultant biologic activity of angiotensin II or its metabolites such as angiotensin(1-7) and angiotensin(3-8) may be more directed to other angiotensin-binding sites. AT1 blockers have similar antihypertensive and antiproteinuric effects to those of ACE inhibitors and they may prove to be as useful as ACE inhibitors in delaying progression of renal disease. Because ACE inhibitors and AT1 blockers inhibit the renin-angiotensin system by different mechanisms, there is a possibility that combining them in clinical practice may prove efficacious for lowering blood pressure and for providing target organ protection.