Functional distribution of alpha 1- and alpha 2-adrenergic receptors in the coronary microcirculation.

Abstract

BACKGROUND The goal of this study was to determine the functional distribution of alpha 1- and alpha 2-adrenergic receptors in the epicardial coronary microcirculation. This goal was accomplished by intracoronary administration of the selective alpha 1-adrenergic agonist phenylephrine and the selective alpha 2-adrenergic agonist BHT-933 during measurements of coronary microvascular diameters in the beating heart. METHODS AND RESULTS Experimental measurements were made under conditions with intact vasomotor tone and during coronary hypoperfusion (i.e., under conditions with autoregulatory mechanisms intact and blunted, respectively). Administration of selective alpha 1- and alpha 2-adrenergic antagonists, prazosin and SKF 104078, respectively, confirmed that the agonists were preferentially activating the desired adrenergic receptor subtype because the vasoconstrictor effects of the agonists were completely blocked by the appropriate antagonist. With baseline coronary vasomotor tone intact, phenylephrine caused constriction (8 +/- 3% decrease in diameter, p less than 0.05) of small coronary arteries (vessels greater than 100 microns in diameter) but did not produce constriction of coronary arterioles (vessels less than 100 microns in diameter). During coronary hypoperfusion, phenylephrine caused constriction (p less than 0.05) of both small coronary arteries and arterioles, 6 +/- 2% and 11 +/- 3% decreases in diameter, respectively. BHT-933 did not cause significant changes in microvascular diameters under control conditions but substantially and selectively decreased arteriolar diameters during hypoperfusion (24 +/- 6% decrease in diameter, p less than 0.05). CONCLUSIONS In the intact, autoregulating coronary circulation, coronary arterioles escape from the effects of adrenergic activation but coronary arteries do not; rather, they can exhibit alpha 1-adrenergic coronary vasoconstriction. During coronary hypoperfusion, when autoregulatory adjustments are blunted, coronary arterioles are sensitive to both alpha 1- and alpha 2-adrenergic agonists, demonstrating significant constrictor responses. Also, the magnitude of coronary alpha 2-adrenergic arteriolar constriction (24% decrease in diameter) is significantly greater than that of alpha 2-adrenergic constriction (11% decrease in diameter) (p less than 0.05). Thus, alpha 1- and alpha 2-adrenergic activation produce different constrictor effects in the coronary microcirculation under baseline conditions when autoregulatory adjustments are intact and during coronary hypoperfusion when autoregulation is blunted. The data suggest that alpha 2-adrenergic receptors are preferentially distributed in arterioles, whereas alpha 1-adrenergic receptors are located throughout the coronary microcirculation. Importantly, the data also suggest that intrinsic autoregulatory adjustments in tone (i.e., autoregulatory escape) can override either alpha 1- or alpha 2-adrenergic constriction in coronary arterioles.