Vasoactive effects of serotonin on proximal coronary arteries in awake dogs

This study evaluates the vasoactive effects and mechanisms of action of serotonin on epicardial arteries in awake dogs chronically instrumented with miniature piezoelectric dimension crystals on the proximal circumflex coronary artery. Serotonin (2-16 micrograms) infused as a bolus in the left atrium effected a dose-related biphasic response, which was characterized by an initial increase in vessel dimension with a peak response at 45-75 seconds, followed by a delayed and more sustained vasoconstriction, with a maximum response at 2-8 minutes. The magnitude of the initial vasodilation was generally greater than the delayed vasoconstriction. The initial vasodilation remained unchanged after selective S2 blockade with ketanserin (0.3 mg/kg) and was only minimally but insignificantly attenuated when flow was held constant but was reduced after S1 and S2 blockade with methysergide (0.25 mg/kg). Selective S2 blockade with ketanserin (0.3 mg/kg) attenuated the delayed vasoconstriction in most but not all dogs; the effect of ketanserin was, however, not significant when the entire group was considered. Selective endothelial denudation effectively eliminated the initial vasodilation response to serotonin and significantly augmented the delayed vasoconstriction when the dogs were studied 1-2 days after denudation. The data indicate that in the awake dog, serotonin effects a biphasic vasomotor response characterized by an initial vasodilation that is mediated primarily through a direct endothelium-dependent S1 mechanism followed by a delayed vasoconstriction that is probably mediated via a direct S2 effect on the vascular smooth muscle and is attenuated by the normal endothelium.