Protective effect of long-term angiotensin II inhibition

Abstract

Experimental studies indicate that angiotensin II (ANG II) through its type 1 receptor (AT(1)) promotes cardiovascular hypertrophy and fibrosis. Therefore, the aim of this study was to analyze whether chronic long-term inhibition of the renin-angiotensin system (RAS) can prevent most of the deleterious effects due to aging in the cardiovascular system of the normal rat. The main objective was to compare two strategies of ANG II blockade: a converting enzyme inhibitor (CEI) and an AT(1) receptor blocker (AT(1)RB). A control group remained untreated; treatment was initiated 2 wk after weaning. A CEI, enalapril (10 mg.kg(-1).day(-1)), or an AT(1)RB, losartan (30 mg.kg(-1).day(-1)), was used to inhibit the RAS. Systolic blood pressure, body weight, and water and food intake were recorded over the whole experimental period. Heart, aorta, and mesenteric artery weight as well as histological analysis of cardiovascular structure were performed at 6 and 18 mo. Twenty animals in each of the three experimental groups were allowed to die spontaneously. The results demonstrated a significant protective effect on the function and structure of the cardiovascular system in all treated animals. Changes observed at 18 mo of age in the hearts and aortas were quite significant, but each treatment completely abolished this deterioration. The similarity between the results detected with either enalapril or losartan treatment clearly indicates that most of the effects are exerted through AT(1) receptors. An outstanding finding was the significant and similar prolongation of life span in both groups of treated animals compared with untreated control animals.