The possible participation of glutamate and NO/cGMP in the pressor response to 5-HT3 receptor activation in the nucleus tractus solitarii (NTS) was investigated using selective antagonists in urethane-anaesthetized rats. Intra-NTS administration of NMDA and non-NMDA receptor antagonists, but not metabotropic glutamate receptor antagonists, markedly reduced (70%) the increase in blood pressure caused by local application of the potent 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguanide. The 5-HT3 receptor-mediated pressor response was also significantly attenuated by the local blockade of nitric oxide synthase and soluble guanylyl cyclase. These data suggest that ionotropic glutamate receptors and the associated NO/cGMP transduction mechanism contribute downstream to the pressor effect elicited by 5-HT3 receptor stimulation in the NTS.
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