Y-26763 protects the working rat myocardium from ischemia/reperfusion injury through opening of KATP channels.
This investigation was undertaken to determine the possible protection against ischemia afforded by Y-26763, [(-)-(3S,4R)-4-(N- acetyl-N-hydroxyamino)-6-cyano-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran- 3- ol], which has K+ channel-opening properties, in isolated rat hearts under working conditions. This preparation was subjected to 28 min of global ischemia followed by 30 min of reperfusion. Drugs were injected into the aortic cannula prior to ischemia. Compared to control, Y-26763 (1 microM) resulted in a significant recovery of post-ischemic cardiac functions, significant reduction of cellular enzyme loss, and preserved significantly the stocks of cellular high-energy phosphates and the myocyte ultrastructure. These effects of Y-26763 were completely prevented by glibenclamide (10 microM), a specific K+ channel blocker of KATP channels. In non-ischemic conditions, Y-26763 significantly increased coronary flow without affecting cardiac output and heart rate. The data were analyzed statistically by analysis of variance. The results clearly demonstrate that Y-26763 protects the myocardium from ischemic injury by opening KATP channels.
Rahman
F
F
Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
Kato
A
A
Kawahara
K
K
Nakajima
T
T
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D008854:Microscopy, Electron; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D010710:Phosphates / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000959:Antihypertensive Agents; D001578:Benzopyrans; D007004:Hypoglycemic Agents; D010710:Phosphates; D015221:Potassium Channels; D000255:Adenosine Triphosphate; C074338:Y 26763; D005905:Glyburide