title: Mechanisms of protection afforded by preconditioning to endothelial function against ischemic injury.
abstract: The aim of this study was to assess whether the cardioprotective effect of ischemic preconditioning (IPC) on endothelial function in resistance coronary arteries of the rat involves adenosine and/or activation of ATP-sensitive K+ channels (KATP channels). Isolated rat hearts perfused under constant-flow conditions were exposed to 30 min of partial ischemia (flow rate 1 ml/min) followed by 20 min of reperfusion. Preconditioning was performed with 5 min of ischemia and 10 min of reperfusion before the 30-min ischemia. After the 20-min reperfusion period, coronary arteries were precontracted with U-46619 (0.1 microM), and the coronary response to the endothelium-dependent vasodilator serotonin (5-HT; 10 microM) was compared with that of the endothelium-independent vasodilator sodium nitroprusside (SNP; 3 microM). KATP channels or adenosine receptors were blocked with perfusion of either glibenclamide (0.3 microM) or 8-phenyltheophylline (8-PT; 5 microM), respectively, starting 15 min before IPC or a corresponding sham period. In untreated hearts, ischemia selectively diminished 5-HT-induced vasodilation, compared with sham hearts (without ischemia). The vasodilation by SNP was unaffected after ischemia and reperfusion. Preconditioning in untreated hearts preserved the vasodilation produced by 5-HT. Treatment of hearts with either glibenclamide or 8-PT halved the vasodilation produced by both 5-HT and SNP in sham hearts. Glibenclamide reduced by one-half, whereas 8-PT completely blocked, the protective effect of IPC on endothelium-dependent vasodilation. These results suggest that IPC affords protection to endothelial function in resistance coronary arteries of the rat partially by activation of KATP channels. Adenosine plays a major role in that protection.
authors.affiliation: Faculté de Pharmacie, Université de Montréal, Quebec, Canada.
authors.forename: J F
authors.initials: JF
authors.lastname: Bouchard
authors.forename: D
authors.initials: D
authors.lastname: Lamontagne
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D026902:Potassium Channel Blockers; D015221:Potassium Channels; D058915:Purinergic P1 Receptor Antagonists; D000255:Adenosine Triphosphate; D013806:Theophylline; C028322:8-phenyltheophylline; D005905:Glyburide