title: Glibenclamide-induced blockade of ischemic preconditioning is time dependent in intact rat heart.
abstract: The ATP-sensitive potassium (KATP) channel has been demonstrated to be a potential mediator of ischemic preconditioning (PC) in most species, with the exception of the rat. This conclusion is based on the failure of the KATP channel antagonist glibenclamide (Glib) to block PC in this species. However, previous studies did not take into consideration the kinetic properties of Glib binding to its receptor in the rat myocardium. Therefore, the purpose of the present study was to test the hypothesis that ischemic PC is mediated by the myocardial KATP channel in the rat and that blockade of PC by Glib is a time-dependent phenomenon. Barbiturate-anesthetized, open-chest male Wistar rats were subjected to 30 min of occlusion and 2 h of reperfusion. Ischemic PC was elicited by three 5-min occlusion periods interspersed with 5 min of reperfusion. Infarct size (IS) as a percentage of the area at risk (AAR; IS/AAR) was determined with triphenyltetrazolium staining. PC and the KATP channel opener nicorandil (50 micrograms.kg-1.min-1 i.v.) resulted in marked reductions in IS/AAR from 53 +/- 3% to 8 +/- 1% and 17 +/- 5%, respectively (P < 0.05). Two doses of Glib (1 or 0.3 mg/kg i.v.) given 30 min before PC abolished the protective effect of PC; however, Glib (0.3 mg/kg i.v.) given 5 min before PC failed to block the effect. Glib administered 30 min before the 15-min nicorandil infusion blocked the cardioprotective effect of NC but did not block its transient hypotensive effect. These results demonstrate that the KATP channel is involved in ischemic PC in the intact rat heart and that the inhibitory effect of Glib to block PC is time dependent.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Schultz
authors.forename: Z
authors.initials: Z
authors.lastname: Yao
authors.forename: I
authors.initials: I
authors.lastname: Cavero
authors.forename: G J
authors.initials: GJ
authors.lastname: Gross
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents; D001786:Blood Glucose / Q000032:analysis; D005905:Glyburide / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced; D019194:Ischemic Preconditioning; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives; D020108:Nicorandil; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D000959:Antihypertensive Agents; D001786:Blood Glucose; D009536:Niacinamide; D020108:Nicorandil; D005905:Glyburide