Intrathecal administration of non-NMDA receptor agonists increases arterial pressure and heart rate in the rat.
We have found that spinal NMDA receptors are involved in control of sympathetic output in pathways to the heart and vessels. The present study was done to determine whether spinal non-NMDA excitatory amino acid receptors participate in cardiovascular regulation. Experiments were done on urethane-anesthetized Sprague-Dawley rats, giving the non-NMDA receptor agonists, quisqualate and kainate, and the antagonist, kynurenate, intrathecally at the spinal T9 level. Both quisqualate (30 nmol; n = 7; to activate AMPA receptors) and kainate (2 nmol; n = 6; to activate K receptors) increased arterial pressure and heart rate. The responses were characterized by a rapid onset, achieving, in most cases, greater than 80% of the maximum response within 1-4 min, and a persistence throughout the remaining 20-24 min of the experiment. I.v. injection of hexamethonium (10 mg/kg) prevented the effects of intrathecal administration of quisqualate (n = 5) but not of kainate (n = 7). To determine whether the hexamethonium-resistant effects of kainate were due to a peripheral action, kainate was given i.v. (n = 6); it was found to be without effect on arterial pressure or heart rate. The increases in arterial pressure and heart rate produced by intrathecal administration of quisqualate (30 nmol; n = 6), kainate (2 nmol; n = 6), glutamate (1 mumol; n = 6) and NMDA (2 nmol; n = 6) but not carbachol (27.4 nmol; n = 6) were prevented by similar preadministration of kynurenate (125 nmol). Intrathecal administration of kynurenate (125 nmol; n = 6; 500 nmol; n = 7) decreased arterial pressure and/or heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology, McGill University, Montreal, Que., Canada.
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Henry
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002217:Carbachol / Q000494:pharmacology; D005725:Ganglia, Autonomic / Q000187:drug effects; D005730:Ganglionic Blockers / Q000494:pharmacology; D005971:Glutamates / Q000008:administration & dosage; D018698:Glutamic Acid; D006339:Heart Rate / Q000187:drug effects*; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007278:Injections, Spinal; D007608:Kainic Acid / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D007736:Kynurenic Acid / Q000008:administration & dosage; D008297:Male; D016202:N-Methylaspartate / Q000008:administration & dosage; D016318:Quisqualic Acid / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D005730:Ganglionic Blockers; D005971:Glutamates; D006584:Hexamethonium Compounds; D011978:Receptors, Nicotinic; D018738:Hexamethonium; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D002217:Carbachol; D007736:Kynurenic Acid; D007608:Kainic Acid