Hypertension and diabetes mellitus commonly occur together. Unfortunately, very few randomized, controlled trials of antihypertensive treatment have been carried out in diabetic patients. Thus, decisions regarding the efficacy of such treatment must be based upon evidence, often controversial, extrapolated from studies in non-diabetic populations. A classic example can be seen in studies on the effect of antihypertensive therapy on lipids. Although abnormal myocardial lipid metabolism is a serious complication of diabetes mellitus and is strongly implicated in diabetes-induced primary cardiomyopathy, studies on antihypertensive therapy-induced lipid abnormality are confined to the development of atheroscelerosis and ischemic heart disease. We believe that the effect of antihypertensive agents on lipid metabolism in the cardiovascular system is not limited to the blood where they either have no effect, adversely affect or have a beneficial effect on lipid levels, but also extends to the myocardium, where they also influence lipid levels. Further, this alteration in myocardial lipid metabolism is associated with changes in cardiac contractile performance. In this regard, it is our hypothesis that the beneficial effect of captopril on lipid metabolism in the circulation is not confined to the blood where it decreased total cholesterol, triglycerides, and low density lipoproteins (LDL) as well as increased high density lipoproteins (HDL), but is also beneficial to the myocardium where it likewise positively influences lipid metabolism. This study will, therefore, provide evidence to support this hypothesis. It will assess the effect of captopril on myocardial lipid metabolism of the diabetic-hypertensive rat. Specifically, it will assess the effect of this agent on myocardial levels of cholesterol, triglycerides and long chain acyl carnitines and CoAs. These lipids and lipid intermediates accumulate in the diabetic heart and are strongly implicated in its depressed contractile performance. The male spontaneously hypertensive rat (SHR) will be the animal model. It will be made diabetic with a single tail vein injection of streptozotocin (60 mg/kg). Captopril will be administered in the drinking water (100 mg/kg) 3 days after diabetes induction. Rats will be sacrificed after 6 weeks of diabetes with sodium pentobarbital (75 mg/kg, i.p.). This study will present new findings about captopril therapy during diabetes plus hypertension.
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