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 mmHg, 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/10 microliters) reduced the arterial pressure from 101 to 68 mmHg and heart rate from 364 to 330 beats/min. Parabrachial pressor responses were virtually eliminated after spinal administration of D-AP7 while tachycardic 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 tachycardic 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 further, that excitatory amino acid neurotransmitters in the spinal cord may play a significant role in central cardiovascular regulation.
Bazil
M K
MK
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322.
Gordon
F J
FJ
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000596:Amino Acids / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D007275:Injections, Intravenous; D007278:Injections, Spinal; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D000596:Amino Acids; D000927:Anticonvulsants; D016194:Receptors, N-Methyl-D-Aspartate; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid