Submitted on November 28, 2006
Accepted on January 15, 2007
Sex-specific and exercise-acquired cardioprotection are abolished by sarcolemmal KATP channel blockade in the rat heart
Adam J Chicco1, Micah S Johnson1, Casey J Armstrong1, Joshua M Lynch1, Ryan T Gardner1, Geoffrey S. Fasen1, Cody P Gillenwater1, and Russell L. Moore1*
1 Integrative Physiology, University of Colorado at Boulder, Boulder, Colorado, United States
* To whom correspondence should be addressed. E-mail: russell.moore{at}colorado.edu.
The present study was conducted to determine if the infarct sparing effect of short-term exercise is dependent on the operation of the myocardial sarcolemmal KATP channel. Adult male and female Sprague-Dawley rats were exercised on a motorized treadmill for 5 days. 24 h 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 percent 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 the 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 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 had no effect on infarct size the 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.
