Cardiovascular effects of captopril and enalapril in obese Zucker rats.
The effects of two weeks of oral administration of the angiotensin-converting enzyme inhibitors captopril (a sulphydryl-containing drug) and enalapril (which lacks the sulphydryl group) on skeletal muscle glucose uptake, arterial blood pressure, cardiac hypertrophy, proteinuria and aortic vascular reactivity in obese Zucker 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-treated 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 and 1.99+/-0.04 mg g(-1)of body weight, respectively). Plasma insulin concentration 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 diaphragms 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 stimulate peripheral glucose uptake in the control group but significantly increased glucose uptake in diaphragms from captopril- or enalapril-treated rats (enhancement of glucose uptake vs. control: 52% and 43%, respectively). Endothelium-intact aortic rings from control Zucker rats showed a poor relaxant response to acetylcholine (maximal relaxation of 38.4+/-4.7%). Captopril significantly improved the endothelium-dependent vascular relaxation responses to acetylcholine and the endothelium-independent relaxation to the nitric oxide donor sodium nitroprusside whereas enalapril did not modify these relaxant responses. Neither captopril nor enalapril significantly affected the vascular contractile responses to the vasoconstrictors noradrenaline or KCl. In conclusion, the angiotensin-converting enzyme inhibitors captopril and enalapril reversed insulin resistance and the associated cardiovascular complications (cardiac hypertrophy, hypertension and proteinuria) in the obese Zucker 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 isolated rat aorta.
Duarte
J
J
Department of Pharmacology, School of Pharmacy, University of Granada, Spain. jmduarte@platon.ugr.es
Martinez
A
A
Bermejo
A
A
Vera
B
B
Gámez
M J
MJ
Cabo
P
P
Zarzuelo
A
A
D000109:Acetylcholine / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology*; D006332:Cardiomegaly / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003964:Diaphragm / Q000378:metabolism; D004656:Enalapril / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D018482:Muscle, Skeletal / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011507:Proteinuria / Q000517:prevention & control*; D051381:Rats; D011924:Rats, Zucker