IMPROVED GLUCOSE-METABOLISM FOLLOWING BLOCKADE OF ANGIOTENSIN-CONVERTING ENZYME BUT NOT ANGIOTENSIN AT(1) RECEPTORS

This study compared the effect of benazepril, an angiotensin converting enzyme inhibitor ([S-(R*,R*)]-3-[[1(ethoxycarbonyl)-3-phenylpropyl]amino]-2,3,4,5- tetrahydro-2-oxo) to valsartan, an angiotensin AT(1) receptor antagonist ((S)-N-valeryl-N-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]-methyl-valine) on glucose metabolism and plasma lipid levels in 11- to 12-week-old conscious spontaneously hypertensive rats. Intraperitoneal infusion of benazepril or valsartan at 1, 3 and 10 mg/kg/day produced dose-related reductions in systolic blood pressure after 12 weeks which were not significantly different from each other. During the infusion, valsartan-treated animals gained weight at the same rate as controls, but all infusion rates of benazepril significantly suppressed normal weight gain, despite both compounds having similar antihypertensive effects. At the end of the 12-week treatment period, benazepril (3 and 10 mg/kg/day) significantly increased glucose disposal but did not significantly affect insulin disposal in insulin/glucose tolerance tests. In contrast, none of the infusion rates of valsartan significantly affected glucose or insulin disposal. Finally, compared to controls benazepril and valsartan were without effect on the fasting basal plasma concentrations of glucose, insulin, triglycerides, total cholesterol and K+. The results demonstrate that angiotensin converting enzyme inhibition and angiotensin AT, receptor antagonism have similar antihypertensive effects, but express differences on body weight gain and insulin-stimulated glucose disposal in the conscious spontaneously hypertensive rat.