Effect of ketanserin on proximal and distal coronary constrictor responses to intracoronary infusion of serotonin in patients with stable angina, patients with variant angina, and control patients.

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Abstract
BACKGROUND: Serotonin, released by aggregating platelets, may contribute to or cause myocardial ischemia by constricting epicardial vessels. Experimental studies suggest that this constriction is mediated by two distinct serotonin receptor subtypes: 5-hydroxytryptamine1-like (S1-like) and 5-hydroxytryptamine2 (S2). METHODS AND RESULTS: To determine the relative contribution of S1-like and S2 receptors to the vasoconstrictor effects of serotonin, we studied the effect of ketanserin (0.75 mg, intracoronary), a selective S2 receptor antagonist, on the constrictor response of human coronary vessels to intracoronary infusions of serotonin. In control patients (n = 7), serotonin (10(-4) mol/l) caused significant (p less than 0.05) constriction only in distal segments, which was significantly (p less than 0.05) inhibited by ketanserin. In stable angina patients (n = 8), serotonin (10(-4) mol/l) caused significant constriction in proximal (p less than 0.01) and distal (p less than 0.01) segments, which was significantly inhibited by ketanserin in proximal (p less than 0.05) but not distal (p = 0.30) segments. In patients with variant angina (n = 3), epicardial occlusion at the site of preexisting stenoses in proximal locations occurred at infused concentrations of 10(-6) (one patient) or 10(-5) (two patients) mol/l. The infusion of the same concentration of serotonin after ketanserin again caused epicardial occlusion. CONCLUSIONS: Our results suggest that functionally important S1-like receptors that mediate vasoconstriction exist in the epicardial vessels of patients with stable or variant angina. Their activation, either at hyperreactive sites in patients with variant angina or in the distal epicardial vessels of patients with chronic stable angina, may contribute to or cause myocardial ischemia when serotonin is released after the intracoronary activation of platelets.