Circulation, Vol 84, 2108-2122, Copyright © 1991 by American Heart Association
WM Chilian
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.
ARTICLES
Functional distribution of alpha 1- and alpha 2-adrenergic receptors in the coronary microcirculation
Department of Medical Physiology, Texas A&M University, College Station.
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