KATP channels in rat heart: blockade of ischemic and acetylcholine-mediated preconditioning by glibenclamide.
The objective of this study was to examine if the opening of ATP-sensitive K+ (KATP) channels play an important role in ischemic preconditioning (PC) in the rat heart. A second goal was to test the role of acetylcholine (ACh) in mimicking PC and test if it could be blocked by KATP antagonist. Glibenclamide, a specific antagonist of the KATP channel, was given as two doses of 0.3 mg/kg each at 60 and 30 min before PC. Six groups of rats were subjected to ischemia and reperfusion (I/R) using these protocols: 1) control (I/R), 30-min ischemia followed by 90-min reperfusion (n = 6 rats); 2) preconditioned hearts given 5-min ischemia 10 min before I/R (n = 9 rats); 3) glibenclamide (0.3 mg/kg) treatment 60 and 30 min before PC (n = 13 rats); 4) glibenclamide treatment before I/R (n = 15 rats); 5) ACh infusion for 5 min (18 micrograms/ml) at a rate of 0.15 ml/min followed by equilibration for 10 min before I/R, n = 13 rats; and 6) glibenclamide treatment before ACh infusion followed by I/R (n = 11 rats). Preconditioning reduced the infarcted area (expressed as percent area at risk) from 42.0 +/- 4.4% in control to 8.7 +/- 6% (mean +/- SE, P < 0.05). Glibenclamide blocked the protection conferred by PC (39.1 +/- 4.5%, P < 0.05) without having a significant effect on control nonpreconditioned hearts. ACh infusion in lieu of PC also reduced infarct size to 25.0 +/- 5.63% (P < 0.05 compared with control), which was again blocked by glibenclamide (44.2 +/- 5.0%, P < 0.05). The data suggest that opening of KATP channels for ischemic and ACh-mediated preconditioning is also important in the rat heart.
Qian
Y Z
YZ
Eric Lipman Laboratories of Molecular and Cellular Cardiology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.
Levasseur
J E
JE
Yoshida
K
K
Kukreja
R C
RC
D000109:Acetylcholine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D005905:Glyburide / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D009203:Myocardial Infarction / Q000473:pathology; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D000109:Acetylcholine; D005905:Glyburide