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: T Miki, T Miura, R Bünger, K Suzuki, J Sakamoto, K Shimamoto
• Journal: The American journal of physiology (Am J Physiol) Vol. 275 Issue 4 Pg. H1329-37 (10 1998) ISSN: 0002-9513 [Print] United States
• PMID: 9746483 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Purinergic P1 Receptor Antagonists
• alpha,beta-methyleneadenosine 5'-diphosphate
• Adenosine Monophosphate
• Adenosine Diphosphate
• Theophylline
• 8-phenyltheophylline
• 5'-Nucleotidase

Topics

• 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)
• Purinergic P1 Receptor Antagonists
• Rabbits
• Theophylline (analogs & derivatives, pharmacology)