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

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 292; no. 5; pp. H2432 - H2437
• Main Authors: Chicco, Adam J, Johnson, Micah S, Armstrong, Casey J, Lynch, Joshua M, Gardner, Ryan T, Fasen, Geoff S, Gillenwater, Cody P, Moore, Russell L
• Format: Journal Article
• Language: English
• Published: United States 01.05.2007
• Subjects: Animals; Benzamides - pharmacology; Exercise Therapy - methods; Female; Heart - drug effects; Heart - physiopathology; Male; Myocardial Reperfusion Injury - physiopathology; Myocardial Reperfusion Injury - therapy; Physical Conditioning, Animal - methods; Potassium Channels - drug effects; Potassium Channels - metabolism; Rats; Rats, Sprague-Dawley; Sex Factors; Treatment Outcome
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.01301.2006

Department of Integrative Physiology, University of Colorado Cardiovascular Institute, University of Colorado, Boulder, Colorado Submitted 28 November 2006 ; accepted in final form 15 January 2007 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 + (K ATP ) 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 K ATP 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 K ATP 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 K ATP activity during ischemia. ischemia; infarction; sex differences; gender Address for reprint requests and other correspondence: R. L. Moore, Dept. of Integrative Physiology, Univ. of Colorado at Boulder, Boulder, CO 80309 (e-mail: russell.moore{at}colorado.edu )