Spinal cord substance P mediates bicuculline-induced activation of cardiovascular responses from the ventral medulla.

Substance P (SP) and serotonin are contained in ventral medullary projections to the intermediolateral cell column (IML) of the spinal cord, and both neurotransmitters excite sympathetic preganglionic neurons upon injection into the IML. Since gamma-aminobutyric acid (GABA) in the ventral medulla inhibits, and GABA-receptor antagonists excite sympathetic outflow to the cardiovascular system, experiments were done to determine if SP and serotonin in the spinal cord were responsible for mediating these GABAergic effects. Anesthetized rats were either given intrathecal injections of SP antagonists acutely, or pretreated with intrathecal injections of the serotonin neurotoxin, 5,7-dihydroxytryptamine. The effects of these drugs on mean arterial pressure (MAP) and heart rate (HR), as well as their ability to block the responses to topical application of GABA or the GABA antagonist, bicuculline, at the ventral medulla were assessed. Three SP antagonists (50 micrograms) decreased MAP to 2/3 baseline values, but did not change HR. They also blocked the characteristic increases in MAP and HR elicited by application of bicuculline to the ventral medulla. A lower dose (5 micrograms) of a SP antagonist also decreased MAP and blocked the bicuculline-induced increases in MAP and HR, an effect which was reversed in 1-2 h. Neonatal capsaicin treatment reduced the SP content in the dorsal horns of the thoracic spinal cord, but did not affect the cardiovascular responses to intrathecal injection of SP antagonist nor the blockade of bicuculline-induced responses. Intrathecal injection of 5,7-dihydroxytryptamine two weeks prior to the experiments resulted in 56% depletion of serotonin in the thoracic spinal cord, but did not change either basal MAP and HR, nor the responses to bicuculline and GABA applied to the ventral surface of the medulla. These data provide evidence for a role of spinal cord SP in cardiovascular regulation.