Role of NMDA and non-NMDA receptors in the nucleus tractus solitarius in the depressant effect of ethanol on baroreflexes.
Ethanol has been shown to attenuate hemodynamic responses to baroreceptor activation. Because the excitatory amino acid (EAA), L-glutamate (L-Glu), modulates the baroreceptor function within the nucleus tractus solitarius (NTS), the present study investigated whether ethanol-evoked impairment of baroreceptor activity involves blockade of EAA receptors in this area and whether this action involves selective blockade of N-methyl-D-aspartate (NMDA) receptors. Separate groups of urethane-anesthetized Sprague-Dawley rats received graded doses of the EAA receptor agonists, L-Glu, NMDA, kainic acid or alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid microinjected into the NTS before and after systemic administration of ethanol (1 g/kg). Baroreflex-mediated heart rate responses (baroreflex sensitivity, BRS) were tested by phenylephrine in the same rats. Different doses of the agonists were selected so that comparable dose-related depressor and bradycardic responses were obtained. Ethanol significantly attenuated the BRS and the hemodynamic responses elicited by all EAA agonists. However, the attenuation of the hemodynamic responses was more evident with NMDA. This effect was dose related because a dose of 0.1 g/kg of ethanol had no effect on either BRS or hemodynamic responses to NMDA. Whether systemic ethanol attenuated these responses by a peripheral action or interaction with other brain areas that receive input from the NTS was investigated. Microinjection of ethanol (10 micrograms) into the NTS significantly attenuated the BRS and the hemodynamic responses elicited by NMDA microinjected into the same site. In contrast, responses elicited by non-NMDA (kainic acid and alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid) agonists were preserved.(ABSTRACT TRUNCATED AT 250 WORDS)
el-Mas
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MM
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina.
Abdel-Rahman
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D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001933:Brain Stem / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D011311:Pressoreceptors / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017459:Receptors, Amino Acid / Q000187:drug effects* / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000502:physiology; D012018:Reflex / Q000187:drug effects*
D017459:Receptors, Amino Acid; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D015763:2-Amino-5-phosphonovalerate