FACILITATION BY SUBSTANCE-P AND INHIBITION BY (-TUBOCURARINE OF THE 5-HT3 RECEPTOR-MEDIATED BEZOLD-JARISCH REFLEX IN RATS())

The influence of substance P 3 (mu g/kg) and (+)-tubocurarine (850 mu g/kg) on the Bezold-Jarisch reflex in urethane-anaesthetized rats was studied. The Bezold-Jarisch reflex was induced by the 5-HT3 receptor a gonist phenylbiguanide (0.3, 1, 3 and 10 mu g/kg i.v.) and by capsaici n (10 mu g/kg i.v.). The 5-HT3 receptor antagonist ondansetron (10 mu g/kg) abolished the phenylbiguanide- but not the capsaicin-stimulated bradycardia, indicating that phenylbiguanide and capsaicin act via dif ferent trigger mechanisms (5-HT3 receptor-dependent and -independent, respectively). Substance P significantly potentiated the phenylbiguani de- but not the capsaicin-induced decrease in heart rate. Also, when t he phenylbiguanide-induced response was amplified by substance P, it w as abolished by ondansetron. (+)-Tubocurarine inhibited the phenylbigu anide-induced bradycardia, but did not affect the capsaicin-stimulated decrease in heart rate. Our results demonstrate that substance P pote ntiates but (+)-tubocurarine inhibits the 5-HT3 receptor-mediated Bezo ld-Jarisch reflex. Both effects are probably due to direct influences of the drugs on the 5-HT3 receptors on sensory vagal nerves in the hea rt.