Sex-specific and exercise-acquired cardioprotection is abolished by sarcolemmal KATP channel blockade in the rat heart

Abstract

The present study was conducted to determine whether the infarct sparing effect of short-term exercise is dependent on the operation of the myocardial sarcolemmal ATP-sensitive K+ (KATP) channel. Adult male and female Sprague-Dawley rats were exercised on a motorized treadmill for 5 days. Twenty-four hours following the training or sedentary period, hearts were isolated and exposed to 1 h of regional ischemia followed by 2 h of reperfusion on a modified Langendorf apparatus in the presence or absence of the sarcolemmal KATP channel antagonist HMR-1098 (30 μM). Following the ischemia-reperfusion protocol, infarct size was determined as a percentage of the total ischemic zone at risk (ZAR). Short-term exercise reduced infarct size by 24% in males (32 ± 2% of ZAR; P < 0.01) and by 18% in females (26 ± 2% of ZAR; P < 0.05). Sarcolemmal KATP channel blockade abolished the training-induced cardioprotection in both males and females, increasing infarct size to 43 ± 3% and 52 ± 4% of ZAR, respectively. In the absence of HMR-1098, infarct size was significantly lower in sedentary females than in males (33 ± 4% vs. 42 ± 2% of ZAR, respectively; P < 0.01). However, the presence of HMR-1098 abolished this sex difference, increasing infarct size by 58% in the sedentary females ( P < 0.01) but having no effect on infarct size in sedentary males. This study demonstrates that the sex-specific and exercise-acquired resistance to myocardial ischemia-reperfusion injury is dependent on sarcolemmal KATP activity during ischemia.