Sumatriptan provokes coronary artery spasm in patients with variant angina: Possible involvement of serotonin 1B receptor

Background Serotonin (5HT) can induce coronary artery spasm (CAS) in patients with variant angina (VA). We have previously reported that 5HT1B and 5HT2A receptors gene were expressed in human coronary arterial smooth muscle cells and that isolated coronary artery from a patient with VA showed the supersensitivity to sumatriptan (SMT), a 5HT1B/1D receptor agonist. The aim of the present study was to determine whether SMT can provoke CAS directly or indirectly through platelet aggregation in patients with VA. Methods We evaluated the effects of intracoronary infusion of graded concentrations of SMT on coronary arteries in 9 patients, including 5 documented VA and 4 participants with atypical chest pain as control. Results SMT provoked CAS in all patients with VA. SMT could not induce CAS in control. SMT (10− 4 M) caused significant contractions (%diameter of baseline; median [interquartile range], 0 [0–18.4]% in VA, as compared with control (proximal segments; 92.6 [77.9–118.9]%, p < 0.05 vs. VA, distal segments; 92.9 [65.3–158.5]%, p < 0.01 vs. VA). In control, minor dilation occurred at SMT concentration up to 10− 5 M. SMT could induce in vitro platelet aggregation neither in healthy subjects nor in patients with VA. Conclusions These findings suggest that activation of 5HT1B receptor by SMT can induce CAS directly in patients with VA without platelet activation. This is the first report directly demonstrating the effect of 5HT1B receptor activation on human coronary arteries in vivo.