The resveratrol-induced cardiac protection was studied in Zucker obese rats. Rats were divided into five groups: group 1, lean control; group 2, obese control (OC); group 3, obese rats treated orally with 5 mg kg(-1) day(-1) of resveratrol (OR) for 2 wk; group 4, obese rats received 10% glucose solution ad libitum for 3 wk (OG); and group 5, obese rats received 10% glucose for 3 wk and resveratrol (OGR) during the 2nd and 3rd wk. Body weight, serum glucose, and insulin were measured, and then hearts were isolated and subjected to 30 min of ischemia followed by 120 min of reperfusion. Heart rate, coronary flow, aortic flow, developed pressure, the incidence of reperfusion-induced ventricular fibrillation, and infarct size were measured. Resveratrol reduced body weight and serum glucose in the OR compared with the OC values (414 +/- 10 g and 7.08 +/- 0.41 mmol/l, respectively, to 378 +/- 12 g and 6.11 +/- 0.44 mmol/l), but insulin levels were unchanged. The same results were obtained for the OG vs. OGR group. Resveratrol improved postischemic cardiac function in the presence or absence of glucose intake compared with the resveratrol-free group. The incidence of ventricular fibrillation and infarct size was reduced by 83 and 20% in the OR group, and 67 and 16% in the OGR group, compared with the OC and OG groups, respectively. Resveratrol increased GLUT-4 expression and reduced endothelin expression and cardiac apoptosis in ischemic-reperfused hearts in the presence or absence of glucose intake. Thus the protective effect of resveratrol could be related to its direct effects on the heart.