Substance P (SP) is released from the feline nucleus tractus solitarius (NTS) in response to activation of skeletal muscle afferent input. However, there are differing results about SP release from the rostral NTS in response to baroreceptor afferent input. An anti-sense oligonucleotide to feline SP (SP-asODN) was injected directly into the rostral NTS of chloralose-anesthetized cats to determine whether blood pressure or heart rate responses to ergoreceptor activation (muscle contraction) or baroreceptor unloading (carotid artery occlusion) were sensitive to SP knockdown. Control injections included either buffer alone or a scrambled-sequenced oligonucleotide (SP-sODN). Both muscle contractions and carotid occlusions were performed 3, 6 and 12 h after the completion of the oligonucleotide injections. The cardiovascular responses to contractions were significantly attenuated 3 and 6 h after SP-asODN, but not by the injection of the SP-sODN. The cardiovascular responses to contractions returned to control levels 12 h post anti-sense injection. No detectable release of SP (using antibody-coated microprobes) was measured 3 and 6 h after SP-asODN injections and the expression of SP-immunoreactivity (SP-IR) in the NTS was significantly attenuated, as determined by immunohistochemistry procedures. In contrast, neither the injection of SP-asODN nor the s-ODN attenuated the cardiovascular responses to carotid occlusions, or altered the pattern of release of SP from the brainstem. Injection of the SP-sODN did not affect the expression of SP-IR. These results suggest that the SP involved with mediating the peripheral somatomotor signal input to the rostral NTS comes from SP-containing neurons within the NTS. Our results also suggest that SP in the rostral NTS does not play a direct role in mediating the cardiovascular responses to unloading the carotid baroreceptors. We suggest that the SP released during isometric contractions excites an inhibitory pathway modulating baroreceptor input, thus contributing to the increase in mean blood pressure.

Substance P (SP) is associated with metabo- and mechanoreceptor afferent fibers ('ergoreceptors') in skeletal muscle as well as the afferent fibers from carotid sinus baroreceptors. Afferent activity from each of these are at least partially integrated in the nucleus tractus solitarius (NTS). The purpose of this study was to determine whether SP was released from the NTS during acute reflex-induced changes in blood pressure caused by stimulating these receptors. Both the muscle pressor response and the baroreflex were studied in adult cats anaesthetized with α-chloralose. SP antibody-coated microprobes were used to measure the possible release of SP from the NTS. The muscle pressor response caused a release of immunoreactive SP-like substances (irSP) from the rostral medial NTS, as well as the dorsal motor nucleus (DMV) and lateral tegmental field (FTL). This release was not dependent on intact afferent input from the carotid sinus nerve, but was a function of activation of muscle ergoreceptors, since no irSP was released in response to stimulation of the motor nerves after the muscle was paralyzed. There was no detectable release of irSP from the mNTS during carotid artery occlusions (baroreceptor unloading). Baroreceptor activation, induced by the i.v. injection of the vasoconstrictor, phenylephrine, did not cause the release of irSP from the mNTS above resting baseline levels. These data suggest that SP is involved with the mediation of the afferent signal from muscle ergoreceptor fibers in the medial NTS. SP is not involved with the mediation of baroreceptor afferent signaling in the medial NTS. The release of SP in response to ergoreceptors activation may function to excite an inhibitory pathway which inhibits baroreflex signals that would tend to reduce the blood pressure and heart rate during the muscle pressor response.