Cardiovascular effects of captopril and enalapril in obese Zucker rats

The effects of two weeks of oral administration of the angiotensin-converti ng enzyme inhibitors captopril (a sulphydryl-containing drug) and enalapril (which lacks the sulphydryl group) on skeletal muscle glucose uptake, arte rial blood pressure, cardiac hypertrophy, proteinuria and aortic vascular r eactivity in obese tucker rats were evaluated. Captopril (50 mg kg(-1) once daily) and enalapril(10 mg kg(-1)) did not modify body weight gain or food or water intake. Both drugs decreased systolic blood pressure (157 +/- 6, 133 +/- 4 and 136 +/- 3 mm Hg, in vehicle-, captopril- and enalapril-treate d rats, respectively), blood glucose (172 +/- 8 vs. 151 +/- 7 and 158 +/- 5 mg dl(-1) respectively), proteinuria (46 +/- 10 vs. 17 +/- 2 and 18 +/- 2. 5 mg dl(-1), respectively) and heart weight (2.17 +/- 0.03, 1.98 +/- 0.02 a nd 1.99 +/- 0.04 mg g(-1) of body weight, respectively). Plasma insulin con centration was significantly increased by enalapril (17 +/- 2 ng ml(-1) vs. 9 +/- 2) but not by captopril (12 +/- 1). In the absence of insulin, the d iaphragms from captopril- or enalapril-treated rats showed a significantly higher glucose uptake than that of controls (31% and 30% vs, control group, respectively). The presence of insulin in the incubation medium did not st imulate peripheral glucose uptake in the control group but significantly in creased glucose uptake in diaphragms from captopril- or enalapril-treated r ats (enhancement of glucose uptake vs. control: 52% and 43%, respectively). Endothelium-intact aortic rings from control tucker rats showed a poor rel axant response to acetylcholine (maximal relaxation of 38.4 +/- 4.7%). Capt opril significantly improved the endothelium-dependent vascular relaxation responses to acetylcholine and the endothelium-independent relaxation to th e nitric oxide donor sodium nitroprusside whereas enalapril did not modify these relaxant responses. Neither captopril nor enalapril significantly aff ected the vascular contractile responses to the vasoconstrictors noradrenal ine or KCl. In conclusion, the angiotensin-converting enzyme inhibitors cap topril and enalapril reversed insulin resistance and the associated cardiov ascular complications (cardiac hypertrophy, hypertension and proteinuria) i n the obese tucker rat, an animal model of non-insulin-dependent (type II) diabetes mellitus. However, only captopril, but not enalapril, improved the impaired endothelium-dependent and independent relaxant responses in the i solated rat aorta. (C) 1999 Elsevier Science B.V. All rights reserved.