Coronary capillary remodeling in non-insulin-dependent diabetic rats: amelioration by inhibition of angiotensin converting enzyme and its potential clinical implications.

Using Otsuka Long Evans Tokushima Fatty (OLETF) rats, a model of human non-insulin-dependent diabetes mellitus (NIDDM) that exhibits hypertension, obesity, hyperglycemia and hyperlipidemia, the role of local angiotensin II in cardiovascular complications at early stages of NIDDM was characterized. OLETF rats were given an angiotensin converting enzyme (ACE) inhibitor, cilazapril (10 mg/kg/day) or vehicle from the age of 5 weeks to 20 weeks. Arteriolar, intermediate and venular capillary proportions were determined by the double-staining method and levels of collagen and non-collagenous proteins were determined by the selective dye-binding method in heart tissues. In OLETF rats at 20 weeks of age, capillary network remodeling (i.e., an increase in arteriolar portions and a decrease in venular portions) and an increase in collagen content were detected. Cilazapril not only exerted favorable effects on markers of diabetes, but also prevented capillary network remodeling and ameliorated the increase in collagen content. These results suggest that 1) capillary network remodeling and increase in extracellular matrix protein levels precede the onset of overt NIDDM in OLETF rats, and 2) angiotensin II may be involved in the pathogenesis of cardiac complications in the early stages of NIDDM.