Sex differences in myocardial infarct size are abolished by sarcolemmal KATP channel blockade in rat.
This study was conducted to examine the relationship between myocardial ATP-sensitive potassium (K(ATP)) channels and sex differences in myocardial infarct size after in vitro ischemia-reperfusion (I/R). Hearts from adult male and female Sprague-Dawley rats were excised and exposed to an I/R protocol (1 h of ischemia, followed by 2 h of reperfusion) on a modified Langendorff apparatus. Hearts from female rats showed significantly smaller infarct sizes than hearts from males (23 +/- 4 vs. 40 +/- 5% of the zone at risk, respectively; P < 0.05). Administration of HMR-1098, a sarcolemmal K(ATP) channel blocker, abolished the sex difference in infarct size (42 +/- 4 vs. 45 +/- 5% of the zone at risk in hearts from female and male rats, respectively; P = not significant). Further experiments showed that blocking the K(ATP) channels in ischemia, and not reperfusion, was sufficient to increase infarct size in female rats. These data demonstrate that sarcolemmal K(ATP) channels are centrally involved in mechanisms that underlie sex differences in the susceptibility of the intact heart to I/R injury.
Department of Integrative Physiology, Campus Box 354, University of Colorado at Boulder, Boulder, CO 80309, USA.
Micah S
MS
Johnson
Russell L
RL
Moore
David A
DA
Brown
D018528:ATP-Binding Cassette Transporters / Q000187:drug effects*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D054086:KATP Channels; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology*; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000473:pathology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000187:drug effects*; D012727:Sex Characteristics
D018528:ATP-Binding Cassette Transporters; D001549:Benzamides; D054086:KATP Channels; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; C410297:HMR 1098