Adenosine plays an important role in postischemic dysfunction of cardiac sympathetic nerves because exogenously infused adenosine produces and adenosine deaminase prevents “neural stunning.” We examined whether adenosine acts via a specific receptor mechanism to produce neural stunning. Anesthetized dogs were treated with propranolol to attenuate increases in coronary flow due to adrenergic stimulation of myocardial metabolism. A 15-min occlusion of the left anterior descending coronary artery (LAD) attenuated subsequent LAD coronary vasoconstriction to bilateral sympathetic stimulation during reperfusion by 75% (P < 0.05). Coronary infusion of the adenosine-receptor antagonist 8-p-sulfophenyltheophylline (nonspecific), 8-cyclopentyl-1,3-dipropylxanthine (A1 specific), or 3,7-dimethyl-1-propagylxanthine (A2 specific) during LAD occlusion prevented the attenuation of sympathetic coronary constriction. In separate experiments, either the specific adenosine agonist N6-cyclopentyl-adenosine (A1 specific) or CGS-21680 (A2 specific) or a combination of both agonists was infused into the LAD for 15 min. Neither agonist alone attenuated subsequent sympathetic coronary constriction. In contrast, 15 min after the combined administration of both agonists, sympathetic vasoconstriction was reduced. We conclude that adenosine is capable of attenuating neurogenic coronary constriction through a receptor-mediated mechanism. Activation of more than one receptor subtype is necessary to produce neural stunning.
Effects of Adenosine Receptor Subtypes on Hippocampal Extracellular Serotonin Level and Serotonin Reuptake Activity
