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.

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.

Serotonin-Induced Hypercontraction Through 5-Hydroxytryptamine 1B Receptors in Atherosclerotic Rabbit Coronary Arteries

“…On the other hand, some studies have indicated that ketanserin-resistant (or 5-HT 1 ) receptors predominantly participate in constrictions of coronary arteries in patients with atherosclerosis or coronary artery diseases. 8,27,28 Moreover, isolated coronary arteries from patients with variant angina exhibited enhanced susceptibility to SUM as well as serotonin and ergonovine. 11,12 Recent intravascular ultrasound studies have shown that atherosclerosis is present at sites with coronary vasospasm even in the absence of angiographically significant coronary artery disease.…”

Paraoxonase Polymorphism (Gln192Arg) as a Determinant of the Response of Human Coronary Arteries to Serotonin

“…9,10 The angiographic catheter was used for calibration. The mean diameters of proximal and distal segments, identified by their distance from side branches or from the origin of the vessel, were determined.…”

Comparison of contractile responses to 5‐hydroxytryptamine and sumatriptan in human isolated coronary artery: synergy with the thromboxane A2‐receptor agonist, U46619

“…McFadden et al (1992) showed that in patients with variant angina where 5-HT induced spasm at the sites of stenoses as well as in patients with stable angina where 5-HT constricted the distal epicardial coronary arteries, these responses to 5-HT were resistance to ketanserin. While McFadden et al (1992) discussed the limitations of their study, they speculated that more direct evidence for a role of 5-HT,-like receptors in coronary vasospasm may be determined by the use of selective 5-HTIlike agonists such as sumatriptan. In fact, a recent study in man found that intravenous infusion of sumatriptan significantly reduced coronary artery diameter (MacIntyre et al, 1992).…”

“…They found that ketanserin blocked completely both the decrease in large coronary diameter and the increase in flow to the distal bed to intracoronary infusions of 5-HT in patients with and without angiographic evidence of atherosclerosis. In a similar study, however, McFadden et al (1991) included patients with Prinzmetal's angina (diagnosed previously by intracoronary challenge with ergometrine (ergonovine)) and found that intracoronary infusions of 5-HT caused spasm (zero flow) which was resistant to ketanserin (McFadden et al, 1992). Ketanserin does not prevent either ergometrineinduced ischaemia (Freedman et al, 1984) or spontaneous attacks of variant angina (De Caterina et al, 1984) in man and although ergometrine activates many different types of receptors including a-adrenoceptors , both it (Muller-Schweinitzer, 1980;Sakanashi & Yonemura, 1980;Brazenor & Angus, 1981;Holtz et al, 1982), and the antimigraine drug methysergide (Saxena, 1974;Brazenor & Angus, 1981), cause contractions via receptors other than a-adrenoceptors.…”