Endogenous adenosine modulates alpha 2- but not alpha 1-adrenergic constriction of coronary arterioles.
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.
DeFily
D V
DV
Department of Medical Physiology, Texas A & M University College of Medicine, College Station 78843, USA.
Patterson
J L
JL
Chilian
W M
WM
D000241:Adenosine / Q000502:physiology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008856:Microscopy, Fluorescence; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology*; D058915:Purinergic P1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D012016:Reference Values; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D058915:Purinergic P1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D010656:Phenylephrine; C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline; C015603:azepexole; D000241:Adenosine