Alpha 1-adrenoceptor activation mediates the infarct size-limiting effect of ischemic preconditioning through augmentation of 5'-nucleotidase activity

J Clin Invest. 1994 May;93(5):2197-205. doi: 10.1172/JCI117216.

Abstract

We have reported that ischemic preconditioning may limit infarct size by increasing 5'-nucleotidase activity. The present study tested whether alpha 1-adrenoceptor stimulation in ischemic preconditioning mediates the infarct size-limiting effect through augmentation of 5'-nucleotidase activity. The coronary artery was occluded four times for 5 min separated by 5 min of reperfusion (ischemic preconditioning) in 82 dogs. Then the coronary artery was occluded for 90 min followed by 6 h of reperfusion. Infarct size normalized by risk area was smaller after ischemic preconditioning than in the control group (40.6 +/- 2.3 vs 6.7 +/- 2.0%, P < 0.001), even though no difference existed in endomyocardial collateral flow during ischemia (8.7 +/- 1.0 vs 8.9 +/- 1.0 ml/100 g per min). Ectosolic and cytosolic 5'-nucleotidase activity was increased after ischemic preconditioning. However, prazosin blunted the infarct size-limiting effect of ischemic preconditioning (infarct size: 42.8 +/- 3.7%). Intermittent alpha 1-adrenoceptor stimulation by methoxamine mimicked the increase in 5'-nucleotidase activity and the infarct size-limiting effect, which were abolished by alpha, beta,-methyleneadenosine 5'-diphosphate. Identical results were obtained in the conscious model (n = 20). Therefore, we conclude that increases in ectosolic 5'-nucleotidase activity due to alpha 1-adrenoceptor activation may contribute to the infarct size-limiting effect of ischemic preconditioning.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5'-Nucleotidase / metabolism*
  • Adaptation, Biological
  • Adenosine / blood
  • Animals
  • Blood Pressure
  • Dogs
  • Endocardium / metabolism
  • Esophagus / metabolism
  • Hemodynamics
  • Methoxamine / pharmacology
  • Myocardial Infarction / enzymology
  • Myocardial Infarction / metabolism*
  • Myocardial Infarction / pathology
  • Myocardial Ischemia / enzymology
  • Myocardial Ischemia / metabolism*
  • Perfusion
  • Prazosin / pharmacology
  • Receptors, Adrenergic, alpha-1 / metabolism*
  • Risk Factors

Substances

  • Receptors, Adrenergic, alpha-1
  • 5'-Nucleotidase
  • Methoxamine
  • Adenosine
  • Prazosin