Cardiovascular effects of substance P peptides in the nucleus of the solitary tract.

Microinjection of the neuropeptide substance P (SP) into the baroreceptor portions of the nucleus of the solitary tract (NTS) caused a dose-dependent decrease in blood pressure (BP) and heart rate (HR), consistent with the putative role for SP as a transmitter in the baroreceptor reflex arc. In contrast, SP elevated BP and HR when microinjected into the adjacent area postrema. Structure-activity studies of effects of SP in the NTS revealed that an aminoterminal heptapeptide fragment of SP could fully reproduce the depressor and bradycardic effects of SP. In contrast, a carboxyterminal hexapeptide fragment of SP significantly elevated both BP and HR. The structural requirements for aminoterminal fragment effects were quite specific in terms of peptide length and sensitivity to D-amino acid substitutions. These findings are consistent with a role for SP as a baroreceptor reflex transmitter and suggest, furthermore, that this action is mediated by the aminoterminal region of SP.