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The 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 micrograms 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.
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