[Blockade of the renin-angiotensin system by a combination of ACE inhibitors and AT1 receptor antagonists].
The results issued from experimental models and randomized controlled clinical trials have shown that the more intense is the blockade of the renin-angiotensin system (RAS), the more effective is the prevention of target organ damage. Combined inhibition of the RAS is aimed at more complete blockade of the system through action at two different sites, angiotensin I converting enzyme (ACE) and AT1 receptors. This is achieved either by neutralizing the rise in renin and angiotensin (Ang) I, which follows the interruption of the Ang II-renin negative feed-back loop, or by directly antagonizing Ang II, whose synthesis is in part independent of the RAS. By comparison with higher doses of single site RAS blockers, a combination of an ACE inhibitor and an AT1 receptor antagonist block more effectively the RAS. After the demonstration of its synergistic or additive blood pressure lowering effects in sodium depleted normotensive subjects and animal models, combined blockade of the RAS was shown to be more efficient than single site RAS blockade: 1. in lowering blood pressure in hypertensive patients; 2. in lowering proteinuria and possibly retarding progression of renal failure in patients with diabetic and non-diabetic nephropathy; 3. finally, in improving left ventricular remodelling, cardiac function status and cardiovascular morbidity and mortality in patients with congestive heart failure. The advantage offered by combining two RAS blockers is to increase the beneficial effect of cardioprotection and nephroprotection which are currently demonstrated with the highest doses of an ACE inhibitor or an AT1 receptor antagonist.
Azizi
Michel
M
Centre d'Investigations cliniques 9201, AP-HP-INSERM, Hôpital Européen Georges Pompidou, 75908 Paris, 15. michel.azizi@egp.ap-hop-paris.fr
D057912:Angiotensin II Type 2 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D025461:Feedback, Physiological / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism; D007668:Kidney / Q000187:drug effects; D023421:Models, Animal; D012084:Renin-Angiotensin System / Q000187:drug effects*
D057912:Angiotensin II Type 2 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors