Impaired coronary reactivity in hearts from diabetic mice

Abstract

Reduced coronary flow reserve (CFR) has been suggested a role in the initiation of diabetic cardiomyopathy in type 2 diabetic patients. We therefore examined the CFR in (db/db) diabetic mice, which are characterized by obesity, hyperglycemia and insulin resistance, and thus are regarded a model of type 2 diabetes. Coronary flow and left ventricular developed pressure (LVDP) were measured online in isolated Langendorff-perfused hearts from these animals before and after a short period (90 s) of global noflow ischemia, as well as after exposure to Na-nitroprusside (NO donor) or adenosine. CFR was calculated as the maximum increase in coronary flow (%) above baseline values. Hearts from non-diabetic (db/+, n=ll) mice showed a transient increase in coronary flow following 90 s no-flow ischemia, with a CFR of 51*6%. These hearts also showed a dose-dependent increase in coronary flow after exposure to nitroprusside or adenosine with a CFR of 4&4% and 60*4%, respectively. In contrast, hearts from diabetic (db/db, n=13) mice exhibited a significantly lower CFR in response to no-flow ischemia (21*4%, ~‘0.05 vs control), and the recovery of basal vascular tone was delayed compared to non-diabetic mice. Moreover, diabetic hearts showed significantly lower response to nitroprusside (27*5%) and adenosine (38*5%) (both ~~0.05 vs control). Finally, longterm treatment (7 wk) of diabetic mice with an antidiabetic drug (BM 17.0744, Roche Pharmaceuticals) did not improve coronary reactivity. These results show that the response of the cardiac vasculature to vasoactive substances are impaired in type 2 diabetic mice.