FUNCTIONAL INTERACTIONS BETWEEN ANGIOTENSIN-II AND SUBSTANCE-P IN THE DORSAL MEDULLA

Low doses of either angiotensin (Ang) II or substance P (SP) microinjected into the medial nucleus tractus solitarii (NTS) produce hypotension and bradycardia, mimicking activation of the baroreceptor reflex. Anatomical evidence suggests that Ang II binding sites in the medial NTS are located presynaptically on vagal afferent fibers that may contain SP and are codistributed with SP binding sites located postsynaptically on intrinsic medial NTS neurons. To evaluate whether the similar cardiovascular effects of Ang II and SP in the medial NTS could involve Ang II-evoked release of SP, we compared the effects of these peptides on the spontaneous activity of medial NTS neurons recorded in vitro and determined whether Ang II evoked release of SP from rat medulla slices. Both Ang II and SP (1-mu-M in artificial cerebrospinal fluid) excited 11 of 40 medial NTS neurons. In these cells, the peak response latency was significantly longer to Ang II than to SP (59.5 +/- 4.7 versus 26.5 +/- 2.4 seconds, p < 0.0001). When rat medulla slices were perfused with Ang II (2-mu-M in Krebs' bicarbonate), release of SP immunoreactivity was increased by 400% over control perfusion with Krebs' solution alone (p < 0.05). We have provided the first evidence for an excitatory action of Ang II on neurons in the NTS of the rat and for excitation by both Ang II and SP of a subset of neurons in the medial NTS. Moreover, we have shown for the first time that Ang II can stimulate the release of SP immunoreactivity from the brain. The longer latency of the Ang II-induced neuronal excitation is consistent with an indirect action of this peptide, such as the release of SP from afferent fibers. These observations suggest that at least a portion of the cardiovascular effects elicited by NTS injections of Ang II may involve an interaction with SP, and they have revealed a functional interaction between Ang II and SP in the dorsal medulla.