Hypertensive diabetic cardiomyopathy in the rat: ultrastructural features

Abstract

We previously described a cohort of diabetic patients with typical congestive cardiomyopathy, in whom myocardial lesions were related to concomitant high blood pressure. To evaluate the association of diabetes mellitus and hypertension in more detail, we studied 4 groups of rats with either no disease, streptozotocin-induced diabetes mellitus, renovascular hypertension, or a combination of hypertension and diabetes. Analysis revealed significant myocardial fibrosis and degeneration in the hypertensive-diabetic group when compared to controls, without an obvious relationship to small vessel lesions. The myocardial alterations appeared similar to those observed in patients with hypertension and diabetes mellitus. Of note, although hypertensive animals had focal moderate lesions, diabetic animals had no pathological changes. To further characterize these histological changes, we performed electron microscopy on the 4 animal groups, which we are reporting in this study. Our analysis of the ultrastructural alterations confirms the previous histological observations. Diabetic animals only had increased cellular lipid, and mild, focal areas of myofibrillolysis, with no significant increases in perivascular and perisarcolemmal basal lamina. Consistent with our light microscopic finding that PAS positive material was associated with interstitial or replacement fibrosis, we noted basal lamina proliferation in the hypertensive and hypertensive-diabetic groups, particularly in areas of scarring. Pericapillary basal lamina was increased to the greatest extent in the hypertensive-diabetics. Qualitative alterations of myocardial cells and muscular blood vessels were similar in both the hypertensive and hypertensive-diabetic animals; however, there were more extensive changes in the latter group. This study provides further evidence that the combination of diabetes mellitus and hypertension produces significantly greater myocardial lesions than with either disease alone, not only at the light microscopic level, but ultrastructurally as well. Although the pathogenesis of this cardiomyopathy is unknown it may be related to abnormalities of the cardiac microcirculation. The prevalence of hypertension in the diabetic population suggests that greater attention should be paid to the combination of these 2 conditions and their effects on the heart.