Skeletal muscle afferent fibres release substance P in the nucleus tractussolitarii of anaesthetized cats

1. The tachykinin substance P was recovered from the commissural subdivisio n of the nucleus tractus solitarii (cNTS) using in vivo microdialysis durin g activation of cardiorespiratory and skeletal muscle receptors in thirteen chloralose-anaesthetized cats. 2. Tetanic muscle contraction was evoked by stimulating L7-S1 ventral roots (n=7). Electrically induced muscle contraction increased mean arterial pre ssure (MAP) by 55 +/- 10 mmHg and heart rate by 29 +/- g beats min(-1). Dur ing contraction the dialysate concentration increased 154% above resting co ntrol levels (from 0.217+/-0.009 to 0.546 +/- 0.023 fmol(100 mu l)(-1), con trol vs. contraction, P<0.05). 3. Loss of cardiorespiratory input following disruption of the carotid sinu s and vagus nerves significantly blunted, but did not abolish, the increase in substance P during muscle contraction (from 0.247,0.022 to 0.351 +/- 0. 021 fmol(100 mu l)-1 control vs. contraction, P < 0.05). Approximately 44% of the substance P release during contraction was independent of cardioresp iratory input transmitted by carotid sinus and vagus nerves. 4. To determine the contribution of cardiorespiratory related neural input on substance P release, an intravascular balloon positioned in the thoracic aorta was inflated to increase arterial pressure (n = 6). Balloon inflatio n increased MAP by 50 +/- 5 mmHg and substance P increased from 0.251. +/- 0.025 to 0.343 +/- 0.028 fmol (100 mu l)(-1) (control vs. balloon inflation , P< 0.05). This increase was completely abolished following interruption o f vagal and carotid sinus nerves (from 0.301 +/- 0.002 to 0.311 +/- 0.004 f mol (100 mu l)(-1), control vs. balloon inflation). This finding shows that neural input from cardiorespiratory receptors (primarily arterial barorece ptors) accounted for 37% of the total substance P release during muscle con traction. 5. The findings from this study demonstrate that activation of skeletal mus cle receptors and cardiorespiratory receptors (predominantly arterial baror eceptors) increases the extraneuronal concentration of substance P in the c NTS. Because substance P release was not completely abolished during muscle contraction following disruption of carotid sinus and vagus nerves it is p roposed that: (1) afferent projections from contraction-sensitive skeletal muscle receptors may release substance P in the NTS; (2) neural input from muscle receptors activates substance P-containing neurones within the NTS; and (3) convergence of afferent input from skeletal muscle receptors and ar terial baroreceptors onto substance P-containing neurones in the cNTS facil itates the release of substance P. The role of tachykininergic modulation o f cardiorespiratory input is discussed.