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

Background A high-cholesterol (HC) diet increases blood pressure and induce s renal injury in rats. We compared the effects of alacepril, an ACE inhibi tor, and amlodipine, a Ca antagonist, on the renal injury induced by an HC diet in rats. Design and methods Male Sprague-Dawley rats were given either an HC diet on ly (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, malondial dehyde (MDA) as a parameter for lipid peroxidation and urinary protein excr etion were determined at 0, 4 and 8 weeks. The renal injury was evaluated h istologically by the glomeruli sclerosing score. Results The HC diet increased SEP. Amlodipine lowered SEP more significantl y than alacepril. Serum total cholesterol was increased by the HC diet and was not affected by either anti-hypertensive agent. HDL-cholesterol was sim ilarly decreased in the three HC diet groups. Alacepril, but not amlodipine , completely attenuated the MDA elevation induced by the HC diet. Urinary p rotein excretion was decreased by the two anti-hypertensive agents at a sim ilar rate. The renal histological injury assessed by the sclerosing score w as ameliorated more significantly by alacepril than by amlodipine. Conclusions Both amlodipine and alacepril decreased blood pressure and urin ary protein, and ameliorated the renal injury induced by the HC diet in rat s. The renal effect of alacepril seems to be mediated by the decrease in ox idative stress as well as by reduction of blood pressure, since alacepril l owered the sclerosing score more than amlodipine and completely attenuated MDA, although the blood pressure reduction by alacepril was less than that by amlodipine. (C) Lippincott Williams & Wilkins.