Regulation of coronary resistance vessels and large coronary arteries

Abstract

There is now considerable evidence for α-adrenergic regulation of coronary resistance vessels and large coronary arteries based on studies of chronically instrumented, conscious animals. Infusion of norepinephrine at low doses causes reduction of coronary blood flow with a slight increase in arterial pressure, indicating intense coronary vasoconstriction. This coronary constrictor response was reversed to coronary vasodilation with infusion of norepinephrine after α-adrenergic blockade. Stimulation of α 1- and α 2-adrenergic receptors with phenylephrine and B-HT 920, respectively, also increased calculated coronary vascular resistance in the conscious animal. These effects were eliminated by selective α 1-adrenergic blockade with prazosin and by selective α 2-adrenergic blockade with rauwolscine. Stimulation of the carotid chemoreceptor reflex elicits a period of intense coronary vasoconstriction, characterized by a decrease in coronary blood flow despite increased arterial driving pressure. This response was eliminated by prior α-adrenergic blockade or a combination of cardiac sympathetic denervation and adrenalectomy. Using chronically implanted ultrasonic crystals to measure the epicardial coronary diameter instantaneously and continuously in conscious dogs, marked vasodilation of the large coronary arteries was observed with administration of nitroglycerin or calcium-channel antagonists; in contrast, activation of α-adrenergic receptors with methoxamine induced substantial constriction, characterized by a reduction in coronary artery diameter in the face of elevated distending pressure. The regulation of large coronary arteries is further complicated by the fact that these vessels are responsive to changes in myocardial metabolic demands and coronary blood flow. This was demonstrated by examining responses to brief periods of myocardial ischemia, which induced intense reactive dilation, i.e., dilation of the large coronary artery immediately after the reactive hyperemia response. The dilation of the large coronary artery was not observed after brief periods of myocardial ischemia, when the marked increase in coronary blood flow (reactive hyperemia) was prevented. These findings suggest that coronary artery vasconstriction may be more intense under conditions in which blood flow cannot increase, for example, in the presence of severe stenoses.