title: Role of activation of ectosolic 5'-nucleotidase in the cardioprotection mediated by opening of K+c channels.
abstract: We tested the hypothesis that the opening of ATP-sensitive K+ channels contributes to activation of ectosolic 5'-nucleotidase and the infarct size-limiting effect of ischemic preconditioning. In open-chest dogs, the left anterior descending coronary artery was occluded four times for 5 min each, separated by a 5-min period of reperfusion (ischemic preconditioning, n = 8). After this procedure, the coronary artery was occluded for 90 min, followed by 6 h of reperfusion. Infarct size was smaller in this group than in the group (control, n = 8) with a 45 min interval instead of the ischemic preconditioning procedure (40.1 +/- 3.9 vs. 6.4 +/- 1.9%). Glibenclamide blunted the infarct size-limiting effect of ischemic preconditioning (infarct size, 37.3 +/- 5.8%; n = 7), and transient exposures to cromakalim and nicorandil mimicked it [infarct size, 10.1 +/- 3.1 (n = 7) and 11.1 +/- 2.7% (n = 8), respectively]. Ectosolic and cytosolic 5'-nucleotidase activity increased in the ischemic preconditioning group compared with that in the control group; this preconditioning-induced increase in 5'-nucleotidase activity was blunted by glibenclamide (n = 5) and mimicked by cromakalim (n = 5) and nicorandil (n = 5). The infarct size-limiting effect due to cromakalim and nicorandil was blunted by alpha,beta-methyleneadenosine 5'-diphosphate, an inhibitor of ectosolic 5'-nucleotidase [infarct size, 37.7 +/- 5.6 (n = 9) and 36.8 +/- 4.8% (n = 7), respectively] and 8-sulfophenyltheophylline (infarct size with cromakalim, 44.7 +/- 4.6%; n = 7). We conclude that activation of ectosolic 5'-nucleotidase due to the openers of ATP-sensitive K+ channels contributes to the infarct size- limiting effect of ischemic preconditioning.
authors.affiliation: First Department of Medicine, Osaka University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kitakaze
authors.forename: T
authors.initials: T
authors.lastname: Minamino
authors.forename: K
authors.initials: K
authors.lastname: Node
authors.forename: K
authors.initials: K
authors.lastname: Komamura
authors.forename: Y
authors.initials: Y
authors.lastname: Shinozaki
authors.forename: M
authors.initials: M
authors.lastname: Chujo
authors.forename: H
authors.initials: H
authors.lastname: Mori
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: M
authors.initials: M
authors.lastname: Hori
authors.forename: T
authors.initials: T
authors.lastname: Kamada
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D004285:Dogs; D004789:Enzyme Activation / Q000187:drug effects; D005905:Glyburide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006439:Hemodynamics; D009203:Myocardial Infarction / Q000473:pathology; D017202:Myocardial Ischemia / Q000503:physiopathology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D020108:Nicorandil; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology; D012008:Recurrence
chemical_list: D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D009536:Niacinamide; D020108:Nicorandil; D000255:Adenosine Triphosphate; D015720:5'-Nucleotidase; D005905:Glyburide