BLOCKADE OF PARABRACHIAL PRESSOR-RESPONSES BY SPINAL ADMINISTRATION OF AN N-METHYL-D-ASPARTIC ACID RECEPTOR ANTAGONIST

The purpose of these studies was to investigate a potential role for N-methyl-d-aspartic acid (NMDA) receptors in the spinal cord, in the mediation of pressor responses, evoked by electrical stimulation of supraspinal pressor sites. Graded electrical stimulation (10-40 Hz) of the lateral parabrachial complex increased the mean arterial pressure by 19 to 59 nunHg, and heart rate by 4 to 12 beats/min. Intrathecal administration of the NMDA receptor antagonist D-2-amino-7-phosphonoheptanoic acid (D-AP7; 200 nmol/10μl) reduced the arterial pressure from 101 to 68mmHg and heart rate from 364 to 330 beats/min. Parabrachial pressor responses were virtually eliminated after spinal administration of D-AP7 while tachycardie responses were not significantly affected. Neither intravenous administration of D-AP7 nor intrathecal infusion of vehicle had any effect on parabrachial pressor responses. Intrathecal infusion of NMDA (50 nmol) increased arterial pressure by 43 mmHg and heart rate by 53 beats/min. Intrathecal infusion of kainic acid (3 nmol) increased arterial pressure by 38 mmHg and heart rate by 54 beats/min. Intrathecal infusion of D-AP7 eliminated the pressor and tachycardie actions of NMDA, without affecting those of kainic acid. These results suggest that the maintenance of sympathetic vasomotor tone as well as the mediation of pressor responses produced by electrical stimulation of the parabrachial complex, is dependent upon synaptic activation of spinal NMDA receptors and furthr, that excitatory amino acid neurotransmitters in the spinal cord may play a significant role in central cardiovascular regulation. © 1990.