Effects of alacepril and amlodipine on the renal injury induced by a high-cholesterol diet in rats.

Abstract

A high-cholesterol (HC) diet increases blood pressure and induces renal injury in rats. We compared the effects of alacepril, an ACE inhibitor, and amlodipine, a Ca antagonist, on the renal injury induced by an HC diet in rats. Male Sprague-Dawley rats were given either an HC diet only (n = 5), an HC diet and amlodipine (n = 10) or an HC diet and alacepril (n = 10). The control rats (n = 5) were given a normal diet Systolic blood pressure (SBP) was measured by a tail-cuff method. Serum lipids, malondialdehyde (MDA) as a parameter for lipid peroxidation and urinary protein excretion were determined at 0, 4 and 8 weeks. The renal injury was evaluated histologically by the glomeruli sclerosing score. The HC diet increased SBP. Amlodipine lowered SBP more significantly than alacepril. Serum total cholesterol was increased by the HC diet and was not affected by either anti-hypertensive agent. HDL-cholesterol was similarly decreased in the three HC diet groups. Alacepril, but not amlodipine, completely attenuated the MDA elevation induced by the HC diet. Urinary protein excretion was decreased by the two anti-hypertensive agents at a similar rate. The renal histological injury assessed by the sclerosing score was ameliorated more significantly by alacepril than by amlodipine. Both amlodipine and alacepril decreased blood pressure and urinary protein, and ameliorated the renal injury induced by the HC diet in rats. The renal effect of alacepril seems to be mediated by the decrease in oxidative stress as well as by reduction of blood pressure, since alacepril lowered the sclerosing score more than amlodipine and completely attenuated MDA, although the blood pressure reduction by alacepril was less than that by amlodipine.