title: Ecto-5'-nucleotidase is not required for ischemic preconditioning in rabbit myocardium in situ.
abstract: This study tested the hypothesis that cardiac ecto-5'-nucleotidase (ecto-5'-NT) activity during ischemic preconditioning (PC) contributes to augmented tolerance against ischemia, thereby reducing infarct size in the rabbit heart in situ. The effects of alpha,beta-methylene-adenosine diphosphate (AOPCP), a selective inhibitor of ecto-5'-NT, on cardiovascular responses to AMP were measured to establish in vivo activities of the enzyme and its inhibitor. Left atrial infusion of AOPCP (0.75 mg . kg-1 . min-1) raised AOPCP plasma levels to 138 microM; under these conditions negative chronotropic and inotropic effects of AMP were blocked, demonstrating essentially full inhibition of ecto-5'-NT in the heart in situ. This AOPCP-blocked heart in situ model was used to examine the proposed contribution of ecto-5'-NT in ischemic PC. Myocardial infarction caused by 30-min ischemia was followed by 3-h reperfusion. Infarct size (IS) was measured and expressed as a percentage of the size of the area at risk (%IS/AR). In untreated controls, %IS/AR was 38.1 +/- 3.8%; PC (5-min ischemia, 5-min reperfusion) markedly reduced %IS/AR to 10.0 +/- 2.0%. Essentially identical IS reductions by PC were observed in AOPCP-blocked animals (%IS/AR = 13.8 +/- 2.2 and 13.3 +/- 1.8% in rabbits receiving AOPCP at 0.75 and 1.50 mg . kg-1 . min-1, respectively); here plasma AOPCP levels were established before and during PC but not during the subsequent prolonged ischemia. As expected, AOPCP also did not affect %IS/AR in non-PC controls (%IS/AR = 35.5 +/- 3.7%). In contrast but as predicted, adenosine-receptor blockade by 8-phenyltheophylline (10 mg/kg iv) substantially attenuated IS reduction by PC in both AOPCP-blocked and control hearts (%IS/AR = 25.2 +/- 4.3 and 21.8 +/- 2.2%, respectively; P < 0.05 vs. PC alone). The results demonstrate that cardiac ecto-5'-NT is not required for ischemic PC against infarction in the rabbit.
authors.affiliation: Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556 Japan.
authors.forename: T
authors.initials: T
authors.lastname: Miki
authors.forename: T
authors.initials: T
authors.lastname: Miura
authors.forename: R
authors.initials: R
authors.lastname: Bünger
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: J
authors.initials: J
authors.lastname: Sakamoto
authors.forename: K
authors.initials: K
authors.lastname: Shimamoto
mesh_terms: D015720:5'-Nucleotidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D019194:Ischemic Preconditioning; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009203:Myocardial Infarction / Q000201:enzymology / Q000503:physiopathology* / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000201:enzymology*; D058915:Purinergic P1 Receptor Antagonists; D011817:Rabbits; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D058915:Purinergic P1 Receptor Antagonists; C523965:alpha,beta-methyleneadenosine 5'-diphosphate; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D013806:Theophylline; C028322:8-phenyltheophylline; D015720:5'-Nucleotidase