Malinowska B, Godlewski G, Buczko W, Göthert M
Zaklad Farmakodynamiki, Akademia Medyezna, Bialystok, Poland.
Eur J Pharmacol. 1996 Nov 14;315(2):159-64. doi: 10.1016/s0014-2999(96)00604-8.
The influence of substance P 3 (microgram/kg) and (+)-tubocurarine (850 micrograms/kg) on the Bezold-Jarisch reflex in urethane-anaesthetized rats was studied. The Bezold-Jarisch reflex was induced by the 5-HT3 receptor agonist phenylbiguanide (0.3, 1, 3 and 10 micrograms/kg i.v.) and by capsaicin (10 micrograms/kg i.v.). The 5-HT3 receptor antagonist ondansetron (10 micrograms/kg) abolished the phenylbiguanide- but not the capsaicin-stimulated bradycardia, indicating that phenylbiguanide and capsaicin act via different trigger mechanisms (5-HT3 receptor-dependent and -independent, respectively). Substance P significantly potentiated the phenylbiguanide- but not the capsaicin-induced decrease in heart rate. Also, when the phenylbiguanide-induced response was amplified by substance P, it was abolished by ondansetron. (+)-Tubocurarine inhibited the phenylbiguanide-induced bradycardia, but did not affect the capsaicin-stimulated decrease in heart rate. Our results demonstrate that substance P potentiates but (+)-tubocurarine inhibits the 5-HT3 receptor-mediated Bezold-Jarisch reflex. Both effects are probably due to direct influences of the drugs on the 5-HT3 receptors on sensory vagal nerves in the heart.
研究了P物质3（微克/千克）和（+）-筒箭毒碱（850微克/千克）对氨基甲酸乙酯麻醉大鼠贝佐尔德-贾里什反射的影响。贝佐尔德-贾里什反射由5-HT3受体激动剂苯乙双胍（0.3、1、3和10微克/千克静脉注射）和辣椒素（10微克/千克静脉注射）诱发。5-HT3受体拮抗剂昂丹司琼（10微克/千克）消除了苯乙双胍刺激的心动过缓，但未消除辣椒素刺激的心动过缓，表明苯乙双胍和辣椒素通过不同的触发机制起作用（分别为5-HT3受体依赖性和非依赖性）。P物质显著增强了苯乙双胍诱导的心率下降，但未增强辣椒素诱导的心率下降。此外，当P物质放大苯乙双胍诱导的反应时，它被昂丹司琼消除。（+）-筒箭毒碱抑制苯乙双胍诱导的心动过缓，但不影响辣椒素刺激的心率下降。我们的结果表明，P物质增强但（+）-筒箭毒碱抑制5-HT3受体介导的贝佐尔德-贾里什反射。这两种作用可能是由于药物对心脏感觉迷走神经上的5-HT3受体的直接影响。
