Sympathetic influence on carotid chemoreceptor response to substance P in the cat

Previous studies have suggested that substance P (SP) may play a role in the carotid chemoreceptor response to hypoxia. Given the data from these studies we speculated that within the carotid body hypoxia might release SP which then acts on the chemosensitive unit. Concomitantly SP might be released in the superior cervical ganglion (SCG) and increase sympathetic outflow to the carotid body by interacting with acetylcholine in the SCG. The resulting vasoconstriction in the carotid body would further increase neural output from the carotid body. Hence we hypothesized that the exogenous SP on the carotid chemoreceptor neural activity would decrease after eliminating preganglionic inflow into the SCG. The hypothesis was tested using anesthetized, paralyzed and artificially ventilated cats. Neural activity from the carotid body (carotid chemoreceptor activity) or from the SCG (ganglioglomerular efferent nerve activity (GGN)) was measured. Close intra-arterial administration of SP (10 micrograms) caused a sustained stimulation of the carotid chemoreceptor activity which was accompanied by a fall in arterial blood pressure. The magnitude and time-course of the carotid body responses were extremely variable among the cats. The duration of increased chemoreceptor activity was significantly shortened after a transection of the cervical sympathetic nerve (CVSN). As a control, the duration of carotid body stimulation produced by the second injection of SP in a group of sham-operated cats was measured. This was essentially the same as the first injection, suggesting that the tachyphylactic effect of SP was negligible. The effects of the commonly used pharmacological agents (nicotine, cyanide, dopamine) on carotid chemoreceptor activity were not affected by the transection of the CVSN, GGN activity was also increased by exogenous SP. These results suggest that the effect of exogenous SP on carotid chemoreceptor activity consists of two components: (1) an initial direct excitatory effect; (2) a slowly developing excitatory effect mediated by the sympathetic outflow to the carotid body. The effects could be augmented by the accompanying hypotension.