Glibenclamide improves postischemic recovery of myocardial contractile function in trained and sedentary rats.
In this study, we sought to determine whether there was any evidence for the idea that cardiac ATP-sensitive K+ (K(ATP)) channels play a role in the training-induced increase in the resistance of the heart to ischemia-reperfusion (I/R) injury. To do so, the effects of training and an K(ATP) channel blocker, glibenclamide (Glib), on the recovery of left ventricular (LV) contractile function after 45 min of ischemia and 45 min of reperfusion were examined. Female Sprague-Dawley rats were sedentary (Sed; n = 18) or were trained (Tr; n = 17) for >20 wk by treadmill running, and the hearts from these animals used in a Langendorff-perfused isovolumic LV preparation to assess contractile function. A significant increase in the amount of 72-kDa class of heat shock protein was observed in hearts isolated from Tr rats. The I/R protocol elicited significant and substantial decrements in LV developed pressure (LVDP), minimum pressure (MP), rate of pressure development, and rate of pressure decline and elevations in myocardial Ca(2+) content in both Sed and Tr hearts. In addition, I/R elicited a significant increase in LV diastolic stiffness in Sed, but not Tr, hearts. When administered in the perfusate, Glib (1 microM) elicited a normalization of all indexes of LV contractile function and reductions in myocardial Ca(2+) content in both Sed and Tr hearts. Training increased the functional sensitivity of the heart to Glib because LVDP and MP values normalized more quickly with Glib treatment in the Tr than the Sed group. The increased sensitivity of Tr hearts to Glib is a novel finding that may implicate a role for cardiac K(ATP) channels in the training-induced protection of the heart from I/R injury.
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Department of Kinesiology and Applied Physiology, University of Colorado Cardiovascular Institute, University of Colorado, Boulder, CO 80309-0354, USA. kjew@spot.colorado.edu
Moore
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D018528:ATP-Binding Cassette Transporters; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D054086:KATP Channels; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017207:Rats, Sprague-Dawley
D018528:ATP-Binding Cassette Transporters; D006360:Heat-Shock Proteins; D007004:Hypoglycemic Agents; D054086:KATP Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; D005905:Glyburide; D002118:Calcium