Baroreceptor - Independent release of substance P in the nucleus tractus solitarius: Role of skeletal muscle afferents

The nucleus tractus solitarius (NTS) is a major brainstem site receiving visceral, somatosensory, and cardiovascular afferents, and is known to perform complex integrative functions. In addition, the neuromodulatory peptide substance P (SP) has been localized in neuronal fibers in the NTS. The purpose of this study was to determine if somatosensory input to the NTS can alter the release of SP in the absence of baroreceptor input in anesthetized cats activation of skeletal muscle afferents during isometric contraction of the triceps surae induced by electrical stimulation of L7-S1 ventral roots reflexly increased arterial blood pressure (MAP) 55±10 mmHg (P<0.002) and heart rate (HR) 29±6 bpm (P<0.005). SP was recovered from the NTS using a microdialysis probe (0.5 mm o.d.) positioned stereotaxically in the commissural subnucleus (cNTS). SP was measured by radioimmunoassay. Twenty minutes of muscle contraction increased the dialysate concentration of SP from 0.217±0.009 to 0.546±0.023 fmol/100μl (P<0.0001). Despite the absence of baroreceptor input following acute sino-aortic deafferentation, muscle contraction increased SP in the cNTS from 0.247±0.022 to 0.351±0.021 fmol/100μl (P<0.01). Maximal release of SP (0.283±0.015 to 1.632±0.128 fmol/100μl) was evoked by perfusing the cNTS with a pH-buffered solution of potassium chloride (150 mM). These findings suggest that skeletal muscle contraction evokes a neurally-mediated release of SP in a region of the NTS known to receive both baroreceptor and skeletal muscle afferent projections. Furthermore, it is postulated that activation of somatosensory afferents can evoke the release of SP in the cNTS independent of excitatory baroreceptor input.