SUMMARYThe pulmonary chemoreflexes evoked by phenylbiguanide (PBG), phenyldiguanide (PDG), phenylguanidine (PG) and 5-hydroxytryptamine (5-HT) have been investigated in the pentobarbitone-anaesthetized rabbit. The rank order of potency was 5-HT > PBG > PG > PDG. The responses evoked by all agonists were antagonized by pre-treatment with the selective 5-HT3 receptor antagonist MDL 72222, suggesting that their reflex effects are mediated by 5-HT3 receptors located on pulmonary vagal afferents. Furthermore, considering the low potency and long injection response time of PDG compared to PBG, we conclude that previous workers have used PBG and not PDG to identify non-myelinated pulmonary vagal afferents and to evoke the pulmonary chemoreflex.

SUMMARYThe effect of the neuronal 5-HT3 receptor antagonist MDL 72222 has been investigated on the reflex tachypnoeic response to pulmonary embolism in pentobarbitone-anaesthetized rabbits.Pre-treatment with MDL 72222 (640 ,tg kg-1, 5 min prior to embolization) significantly attenuated the reflex tachypnoeic response associated with the injection of emboli. MDL 72222 had no effect on the bradycardia associated with embolization; however, it significantly reduced the decrease in arterial blood pressure and converted the decrease in tidal volume seen in pulmonary embolism to an increase. Furthermore, MDL 72222 had no effect on the decrease in circulating platelet count associated with embolization. The data suggest that 5-hydroxytryptamine is of primary importance in mediating the post-embolic increase in respiratory rate seen in this model of pulmonary embolism.

SUMMARYWe have investigated the effects of the intravenous administration of 5-hydroxytryptamine upon the discharge frequency of pulmonary stretch receptors, irritant receptors and C fibres. Only C fibres were stimulated by this autacoid. MDL 72222 a selective 5-HT3 receptor antagonist blocks the C fibre stimulation by 5-hydroxytryptamine. It also blocks the C fibre response to miliary pulmonary embolism. These data confirm the hypothesis that 5-hydroxytryptamine is the humoral link between pulmonary embolism and tachypnoea.