benazepril and Glucose-Intolerance

This study tested whether the angiotensin-converting enzyme inhibitor (ACEI) benazepril can improve the insulin resistance and glucose tolerance in uremia. Fifteen uremic hypertensive patients were treated with benazepril in a dose of 10-20 mg per day for ten weeks, and ten healthy subjects, matched in age, sex ratio and body mass index (BMI), served as the control group. Before and after the treatment, an oral 75 g glucose tolerance test (OGTT) and insulin release test (IRT) were performed in two groups above, and the blood glucose and serum insulin concentrations at 0, 60, 120 and 180 minutes after glucose load were examined, and the insulin glycoregulatory activity, including insulin sensitivity index (ISI), glucose uptake rate (M), total areas under the glucose and insulin curves during OGTTs (AUCG AUCINS), was calculated. The changes of serum potassium and renal function before and after treatment were observed. It showed that (1) benazepril could reduce blood pressure significantly (SBP decreased from 174.8 +/- 12.0 mmHg to 151.5 +/- 9.0 mmHg, p <0.001; DBP decreased from 108.0 +/- 8.2 mmHg to 95.3 +/- 9.0 mmHg, p <0.001). The total response rate was 86.7%. (2) After treatment with benazepril for ten weeks, the blood glucose and serum insulin concentrations after glucose load and AUCG, AUCINS values in the uremic patients were significantly lower than before treatment, but were still significantly higher than in the controls. The values of ISI and M in the uremic patients after treatment were much higher than before treatment, but were still significantly lower than in the control subjects. (3) The differences of serum potassium and creatinine levels before and after treatment were not significant. These findings indicate that benazepril can not only reduce blood pressure effectively and safely, but also partly improve insulin resistance, hyperinsulinemia and glucose intolerance in uremia.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Case-Control Studies; Female; Glucose Intolerance; Humans; Hyperinsulinism; Hypertension, Renal; Insulin Resistance; Male; Middle Aged; Treatment Outcome; Uremia

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 AT1 receptor antagonist ((S)-N-valeryl-N-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]-methyl-valin e) 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 AT1 receptor antagonism have similar antihypertensive effects, but express differences on body weight gain and insulin-stimulated glucose disposal in the conscious spontaneously hypertensive rat.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Benzazepines; Blood Glucose; Blood Pressure; Body Weight; Drug Tolerance; Glucose Intolerance; Hypertension; Insulin Resistance; Lipids; Rats; Rats, Inbred SHR; Tetrazoles; Valine; Valsartan