Intracarotid Substance P infusion inhibits ventilation in the goat

Abstract

Substance P (SP) has been proposed as an excitatory neuromodulator of the carotid body (CB) response to hypoxia based on data from the cat and rat. The role of SP as a CB neuromodulator in the goat is unknown. Awake ( n = 14) and chloralose anesthetized goats ( n = 6) were used to investigate the effects of intracarotid (IC) SP infusions (1–6 μg · kg −1 · min −1) and bolus injections (6 μg · kg −1) to the CB intact and denervated (CBX) sides (control) on mean ventilation (V̇ e) and mean blood pressure (MBP). In awake goats V̇ e was decreased by infusion or bolus SP injection at a dose of 6 μg · kg −1 ( P < 0.05) and occurred with infusions to the intact or CBX sides. MBP was elevated with SP infusion to either the CB intact or CBX sides at all SP doses. The SP antagonist CP — 96,345 (0.1 mg · kg −1,IV) blocked the decrease in V̇ e induced by SP in normoxia and significantly increased the hypoxic ventilatory response (Pa O 2 = 40 torr). In anesthetized goats, IC injections of SP (1 to 6 μg · kg −1) reduced phrenic activity and MBP before and after CBX. In only one of five goats airway pressure was increased suggesting that bronchoconstriction was not a cause for the reduced ventilatory and phrenic activity induced by SP. Immunohistochemistry provided evidence of SP in CB nerve fibers and terminals, carotid sinus nerve axons and petrosal ganglion cells, but not in type I glomus cells. Our results do not support the view that SP is an excitatory neuromodulator of CB chemotransduction in the goat.