Endogenous adenosine modulates alpha 2- but not alpha 1-adrenergic constriction of coronary arterioles

Am J Physiol. 1995 Jun;268(6 Pt 2):H2487-94. doi: 10.1152/ajpheart.1995.268.6.H2487.

Abstract

In the coronary circulation alpha-adrenergic constriction competes with metabolic vasodilation. Because adenosine is produced by the working myocardium and metabolic stimulation results in arteriolar dilation, we tested the hypothesis that coronary arteriolar alpha-adrenergic constriction is attenuated by the endogenous production of adenosine. To test this hypothesis, using fluorescence microscopy during stroboscopic epi-illumination of the epicardial microvasculature, we measured the diameter of coronary arterioles in anesthetized open-chest dogs. Measurements were made in the presence of beta-blockade during selective alpha 1- or alpha 2-adrenoceptor activation (phenylephrine or B-HT-933, respectively) before and in the presence of the nonselective adenosine receptor antagonist 8-p-sulfophenyltheophylline (8-pSPT) and expressed as a percent change in microvascular diameter relative to baseline. alpha 1-Activation produced constriction of coronary arterioles under control conditions, which was not augmented after adenosine antagonism (-12 +/- 2 vs. -7 +/- 3%). In contrast, alpha 2-activation did not constrict coronary arterioles under control conditions; however, blockade of adenosine receptors unmasked a significant constriction (0 +/- 2 vs. -7 +/- 2%, P < 0.05). Also adenosine antagonism did not significantly alter the baseline diameter of coronary arterioles. These results demonstrate that endogenously produced adenosine modulates alpha 2-adrenergic constriction of coronary arterioles but not alpha 1-adrenergic constriction, and therefore we speculate that the competition between alpha-adrenergic constriction and metabolic vasodilation is mediated by the alpha 1-adrenoceptor.

Publication types

  • Comparative Study

MeSH terms

  • Adenosine / physiology*
  • Adrenergic alpha-Agonists / pharmacology
  • Animals
  • Arterioles / drug effects
  • Arterioles / physiology*
  • Azepines / pharmacology
  • Blood Pressure / drug effects
  • Coronary Circulation / drug effects
  • Coronary Circulation / physiology*
  • Coronary Vessels / drug effects
  • Coronary Vessels / physiology*
  • Dogs
  • Female
  • Heart Rate / drug effects
  • Male
  • Microscopy, Fluorescence
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology*
  • Phenylephrine / pharmacology*
  • Purinergic P1 Receptor Antagonists*
  • Receptors, Adrenergic, alpha-1 / physiology*
  • Receptors, Adrenergic, alpha-2 / physiology*
  • Reference Values
  • Theophylline / analogs & derivatives
  • Theophylline / pharmacology
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology*

Substances

  • Adrenergic alpha-Agonists
  • Azepines
  • Purinergic P1 Receptor Antagonists
  • Receptors, Adrenergic, alpha-1
  • Receptors, Adrenergic, alpha-2
  • Phenylephrine
  • 8-(4-sulfophenyl)theophylline
  • Theophylline
  • azepexole
  • Adenosine