EFFECTS OF SUMATRIPTAN ON CORONARY FLOW AND LEFT-VENTRICULAR FUNCTIONIN THE ISOLATED-PERFUSED GUINEA-PIG HEART

The effects of the 5-HT1B/D receptor agonist, sumatriptan, on coronary flow (CF) and left ventricular function in the isolated perfused guin ea pig heart were investigated in the presence and absence of coronary endothelial dysfunction induced by nitric oxide (NO) synthase inhibit ion with N-omega-nitro-L-arginine methyl ester (L-NAME; 10 mu M). Hear ts were perfused under constant pressure (80 cm H2O) with oxygenated ( 95% O-2/5% CO2) Krebs bicarbonate buffer (pH 7.4) and were driven at 4 Hz. In the absence of L-NAME (n = 37), sumatriptan (0.1-32 mu M) fail ed statistically significantly to affect left ventricular developed pr essure (LVDP; maximal change, -8.1 +/- 1.8%; NS vs, vehicle), left ven tricular end-diastolic pressure (LVEDP; +10.4 +/- 9.8%, NS), or CF (-1 2.2 +/- 1.4%; NS compared with vehicle). L-NAME per se significantly r educed coronary flow (CF; -26.3 +/- 2.9%; p < 0.001), thereby increasi ng coronary vascular tone, and decreased LVDP (-17.1 +/- 1.8%; p < 0.0 1). In hearts perfused with L-NAME (10 mu M; n = 61), sumatriptan (0.1 -32 mu M) still failed significantly to affect CF (maximal change, 0.2 +/- 5.7%, NS)but concentration-dependently increased LVEDP [maximal i ncrease, 89.0 +/- 30.3%; p < 0.05; geometric mean EC50 3.6 (2.9-5.7) m u M], which was not prevented by the 5-HT1B/D receptor antagonist, GR 127935 (0.1 mu M; maximal increase: 51.8 +/- 11.1%; n = 48, NS compare d with sumatriptan alone). In conclusion, sumatriptan failed significa ntly to affect CF even in the presence of endothelial dysfunction. LV function similarly remained unaffected in normal hearts, but sumatript an produced diastolic contracture in the presence of coronary endothel ial dysfunction by a mechanism apparently not involving 5-HT1B/D recep tors. Collectively the data indicate that 5-HT1B/D receptor expression or effector coupling or both are absent or low in the guinea pig hear t, because no detectable functional responses were observed.