Mechanisms of protection afforded by preconditioning to endothelial function against ischemic injury.
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.
Bouchard
J F
JF
Faculté de Pharmacie, Université de Montréal, Quebec, Canada.
Lamontagne
D
D
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
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D058915:Purinergic P1 Receptor Antagonists; D000255:Adenosine Triphosphate; D013806:Theophylline; C028322:8-phenyltheophylline; D005905:Glyburide