title: Heat stress-induced protection of endothelial function against ischaemic injury is abolished by ATP-sensitive potassium channel blockade in the isolated rat heart.
abstract: The protection conferred by heat stress (HS) against myocardial ischaemia-reperfusion injury, in terms of mechanical function preservation and infarct size reduction, is well documented and mechanisms underlying these effects have been extensively explored. However, the effect of HS on coronary circulation is less known. The aim of this study was thus to investigate the role of ATP-sensitive potassium (K(ATP)) channels in the protection against ischaemic injury afforded by HS to the coronary endothelial function. Twenty-four hours after whole body hyperthermia (42 degrees C for 15 min, H groups) or sham anaesthesia (Sham groups), isolated perfused rat hearts were subjected to a 15 min stabilization period followed by a 30 min infusion of either 0.3 microM glibenclamide (Gli, a K(ATP) channel blocker) or its vehicle (V). Hearts were then exposed to a low-flow ischaemia (30 min)-reperfusion (20 min) (I/R) or normally perfused (50 min), after which coronaries were precontracted with 0.1 microM U-46619. Finally, the response to the endothelium-dependent vasodilator, 5-hydroxytryptamine (5-HT, 10 microM) was compared to that of the endothelium-independent vasodilator, sodium nitroprusside (SNP, 3 microM). In hearts from Sham-V and Sham-Gli groups, I/R selectively diminished 5-HT-induced vasodilatation without affecting the vasodilatation to SNP. In V-treated groups, prior HS preserved the vasodilatation produced by 5-HT. This HS-induced protection was abolished by Gli treatment. In conclusion, these results suggest that K(ATP) channel activation contributes to the preservation of coronary endothelial function conferred by heat stress against ischaemic insult.
authors.affiliation: Laboratoire du Stress Cardiovasculaire et Pathologies Associées, Faculté de Pharmacie, Université Joseph Fourier, Domaine de la Merci, F38706 La Tronche, France.
authors.forename: M
authors.initials: M
authors.lastname: Joyeux
authors.forename: J F
authors.initials: JF
authors.lastname: Bouchard
authors.forename: D
authors.initials: D
authors.lastname: Lamontagne
authors.forename: D
authors.initials: D
authors.lastname: Godin-Ribuot
authors.forename: C
authors.initials: C
authors.lastname: Ribuot
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005905:Glyburide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D018882:Heat Stress Disorders; D007004:Hypoglycemic Agents / Q000494:pharmacology; D019194:Ischemic Preconditioning; D054086:KATP Channels; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018528:ATP-Binding Cassette Transporters; 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