Hypertensive-diabetic cardiomyopathy in the rat: an experimental model of human disease

The authors recently described a group of diabetic patients with severe congestive heart failure, hypertension, and minimal coronary artery disease, who had significant myocardial degeneration apparently secondary to the combined effects of high blood pressure and diabetes on the heart. To evaluate the effects of hypertension and diabetes mellitus more fully, the authors studied four groups of rats with either no disease, streptozotocin-induced diabetes mellitus, renovascular hypertension, or a combination of hypertension and diabetes. They employed semiquantitative light microscopy, which revealed significantly greater replacement fibrosis in the hypertensive-diabetic rats when compared with the other three groups. Interstitial fibrosis was increased in the hypertensive-diabetic animals, though it was just below the 5% level of significance when compared with the hypertensives. Further analysis, however, revealed that those hypertensive-diabetic animals with the greatest relative cardiac hypertrophy, as measured by the heart weight/body weight ratio, had significantly increased interstitial fibrosis. Surprisingly, diabetes mellitus alone produced no morphologic light-microscopic alterations; yet 8 weeks of combined hypertension and diabetes mellitus led to myocardial degeneration similar to the human disease. These changes do not appear to be secondary to abnormalities of intramyocardial muscular vessels. Measurement of 3 parameters of vascular disease revealed that hypertensive animals with less myocardial damage had greater vascular changes than the more severely affected hypertensive-diabetics. This study provides evidence that the combination of diabetes mellitus and hypertension produces significantly greater myocardial lesions than either disease alone. The similarity of the lesions with those observed in human patients suggests that the hypertensive-diabetic rat is a useful model for elucidating the pathogenesis of clinical myocardial disease in patients with hypertension and diabetes mellitus.