Article: article from journal or magazin.
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Rationale for combining blockers of the renin-angiotensin system.
Seminars in Nephrology
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; ReviewPublication Status: ppublish
Blockade of the renin-angiotensin system (RAS) with angiotensin I-converting enzyme (ACE) inhibitors and AT1-receptor (AT1R) blockers has become one of the most successful therapeutic approaches in medicine. The question is no longer whether RAS inhibition helps, but rather how we can optimize inhibition to achieve optimal cardiovascular and renal protection. Indeed, numerous data have shown that the RAS is not blocked fully over 24 hours with current doses of RAS blockers because they trigger a counter-regulatory renin release that can offset pharmacologic inhibition of the RAS. This absence of full blockade may have clinical implications. Combination therapy with ACE inhibitors and AT1R antagonists thus has been proposed to inhibit the biological effects of the reactive renin release triggered by single-site RAS inhibition. By using this approach, numerous experimental and clinical studies have suggested that this combination therapy has additive or synergistic effects on blood pressure and on the prevention of cardiovascular and renal lesions. Although similar intensity of RAS blockade can be achieved by either combination therapy or by using high doses of an AT1-receptor antagonist given alone, the ACE inhibitor present in the combination interferes with the bradykinin-nitric oxide pathway and the N-acetyl-Ser-Asp-Lys-Pro metabolism, which both may have additional biological effects.
Angiotensin II Type 1 Receptor Blockers/therapeutic use, Angiotensin-Converting Enzyme Inhibitors/therapeutic use, Animals, Blood Pressure/drug effects, Cardiovascular Diseases/metabolism, Cardiovascular Diseases/prevention & control, Drug Therapy, Combination, Humans, Kidney Diseases/metabolism, Kidney Diseases/prevention & control, Renin-Angiotensin System/drug effects, Treatment Outcome
Last modification date