Document Detail


Ecto-5'-nucleotidase is not required for ischemic preconditioning in rabbit myocardium in situ.
MedLine Citation:
PMID:  9746483     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
T Miki; T Miura; R Bünger; K Suzuki; J Sakamoto; K Shimamoto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of physiology     Volume:  275     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1998 Oct 
Date Detail:
Created Date:  1998-11-19     Completed Date:  1998-11-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  H1329-37     Citation Subset:  IM    
Affiliation:
Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556 Japan.
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MeSH Terms
Descriptor/Qualifier:
5'-Nucleotidase / antagonists & inhibitors,  metabolism*
Adenosine Diphosphate / analogs & derivatives*,  pharmacology
Adenosine Monophosphate / pharmacology
Animals
Blood Pressure / drug effects,  physiology
Enzyme Inhibitors / pharmacology
Heart / physiology*
Heart Rate / drug effects,  physiology*
Ischemic Preconditioning*
Male
Myocardial Contraction / drug effects,  physiology*
Myocardial Infarction / enzymology,  physiopathology*,  prevention & control
Myocardial Ischemia / physiopathology*
Myocardial Reperfusion*
Myocardium / enzymology*
Rabbits
Receptors, Purinergic P1 / antagonists & inhibitors
Theophylline / analogs & derivatives,  pharmacology
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Receptors, Purinergic P1; 3768-14-7/adenosine 5'-methylenediphosphate; 58-55-9/Theophylline; 58-64-0/Adenosine Diphosphate; 61-19-8/Adenosine Monophosphate; 961-45-5/8-phenyltheophylline; EC 3.1.3.5/5'-Nucleotidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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