Effect of Chronic Inhibition of Renin-Angiotensin System on Cardiovascular Damage due to Aging in Normal Rats

pp 699-707

Abstract

The present study was performed to assess the effects of either enalapril (E) or losartan (L) given since weaning to normal rats during 6or 18 months.Animals (n = 48) were divided in three groups: control, E treated and L treated. Treated rats received10 mg/kg/day of the selected drug. Half of the rats were studied at 6 months and the rest at 18 months of life. Systolic blood pressure (SBP), body weight (BW), water intake (WI) and food intake(FI) were assessed as, as well as cardiac, left ventricular and aortic weights. A segment of the jejunum-ileum was also isolated. Cardiac fibrosis was evaluated by light microscopy at 100X. The thickness of the aortic wall was measured. NADPH-diaphorase activity was determined as a marker of nitric oxide synthase(NOS)activity in aorta, arterioles of small intestine, heart and kidney of normal rats. NOS activity was measured through the optical density(OD) of the stained tissue. Urinary excretion of nitrates + nitrites was determined. Only significant differences (p < 0.05) are reported. SBP, absolute cardiac, left ventricular and aortic weights increased with age. Renin angiotensin system inhibition delayed these increases. The increase in cardiac fibrosis and aortic thickness, due to aging, was prevented by E. At 6 months L and E enhanced theNO release, which was lower with aging. At 6 and18 months, NOS activity was increased in the aortic endothelium of all treated animals and was lower in aged rats.

Conclusions

Both E and L prevented cardiovascular hypertrophy/hyperplasia and increased NOS activity in the aortic endothelium indicating an action exerted through inhibition of the renin-angiotensin system and pointing out to a protective effect on cardiovascular damage due to aging. E also inhibited myocardial fibrosis and thickening of the aortic wall.