title: 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(+) (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 microM). 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.
authors.affiliation: Department of Integrative Physiology, University of Colorado at Boulder, Boulder, CO 80309, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Chicco
authors.forename: Micah S
authors.initials: MS
authors.lastname: Johnson
authors.forename: Casey J
authors.initials: CJ
authors.lastname: Armstrong
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Lynch
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Gardner
authors.forename: Geoff S
authors.initials: GS
authors.lastname: Fasen
authors.forename: Cody P
authors.initials: CP
authors.lastname: Gillenwater
authors.forename: Russell L
authors.initials: RL
authors.lastname: Moore
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D005081:Exercise Therapy / Q000379:methods*; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology* / Q000628:therapy*; D010805:Physical Conditioning, Animal / Q000379:methods*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; C410297:HMR 1098