Potentiation of non-N-methyl-D-aspartate receptor-induced changes in blood pressure by substance P in rats.

Central release of substance P (SP) in the nucleus tractus solitarius (NTS) may potentiate the reflex responses evoked by baroreceptor afferent input to this medullary nucleus. The mechanism is not known but may involve modulation of responses produced by release of glutamate, the putative primary baroreceptor transmitter, at neurons within the NTS. The principal glutamate receptor subtype proposed to transmit baroreceptor afferent input at second-order neurons is the non-N-methyl-D-aspartate (NMDA) receptor. The present study examined the effects of microinjection of SP into barosensitive regions of the NTS on the depressor and bradycardic response induced by activation of non-NMDA receptors in the NTS by subsequent microinjection of (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), a non-NMDA receptor agonist. Substance P potentiated the non-NMDA receptor-induced depressor response to AMPA in the NTS, evoking a significantly larger change in blood pressure over the same time period. These data suggest that SP may modulate a non-NMDA-miediated component of the baroreflex to influence the control of arterial blood pressure by increasing the sensitivity of the baroreceptor reflex.