Spinal NMDA receptors mediate pressor responses evoked from the rostral ventrolateral medulla.
These studies investigated the role of spinal N-methyl-D-aspartic acid (NMDA) receptors in the mediation of cardiovascular responses evoked by L-glutamate (L-Glu) stimulation of the rostral ventrolateral medulla (RVM). Microinjections of L-Glu into the RVM of urethan-anesthetized rats increased mean arterial pressure (MAP) and heart rate. Intrathecal administration of the NMDA receptor antagonists D-(-)-2-amino-7-phosphonoheptanoic acid (D-AP-7) or 3-((+-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate (CPP) reduced MAP and heart rate. Blockade of NMDA receptors by D-AP-7 or CPP in the caudal thoracic spinal cord markedly reduced RVM pressor responses with little effect on evoked tachycardia. Administration of D-AP-7 to the rostral thoracic spinal cord had no effect on RVM pressor or tachycardic responses. Intrathecal D-AP-7 and CPP abolished the cardiovascular effects of intrathecal NMDA without reducing those produced by intrathecal kainic acid or the quisqualate agonist DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). These results indicate that 1) tonic activation of spinal NMDA receptors participates in the maintenance of sympathetic outflow to the heart and blood vessels, 2) pressor responses evoked from the RVM require synaptic activation of spinal NMDA receptors, and 3) an excitatory amino acid may be the neurotransmitter of pressor pathways descending from the RVM to the spinal cord.
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 / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005971:Glutamates / Q000032:analysis / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000502:physiology*; D013116:Spinal Cord / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology
D000596:Amino Acids; D000927:Anticonvulsants; D005971:Glutamates; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D015763:2-Amino-5-phosphonovalerate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; C031231:2-amino-7-phosphonoheptanoic acid