title: Blockade of L-glutamate receptors in the rostral ventrolateral medulla contributes to ethanol-evoked impairment of baroreflexes in conscious rats.
abstract: This study investigated the effect of ethanol microinjected into the rostral ventrolateral medulla on the cardiovascular responses to intrarostral ventrolateral medulla administration of the excitatory amino acids L-glutamate and N-methyl-D-aspartate (NMDA) and on baroreflex-mediated heart rate responses (baroreflex sensitivity) in conscious freely moving Sprague-Dawley rats. L-Glutamate (5 nmol) or NMDA (25, 50, and 100 pmol) microinjected into the rostral ventrolateral medulla elicited pressor and bradycardiac responses. The cardiovascular responses elicited by both L-glutamate and NMDA were significantly (p < 0.05) attenuated by intrarostral ventrolateral medulla ethanol (10 micrograms) or 2-amino-5-phosphonopentanoic (2 nmol), a selective NMDA receptor antagonist, but not by ACSF. Enhancement of the cardiovascular responses to L-glutamate by intrarostral ventrolateral medulla p-chloromercuriphenylsulfonic acid (0.1 nmol), a glutamate uptake inhibitor, was reversed by subsequent ethanol, but not ACSF, microinjection. None of the treatments influenced baseline blood pressure or heart rate. Ethanol or 2-amino-5-phosphonopentanoic acid microinjected into the rostral ventrolateral medulla significantly (p < 0.05) attenuated baroreflex sensitivity tested by phenylephrine. In contrast, p-chloromercuriphenylsulfonic acid significantly (p < 0.05) enhanced baroreflex sensitivity (-2.14 +/- 0.09 vs. -3.08 +/- 0.18); subsequent ethanol microinjection reversed this enhancement (-2.90 +/- 0.21 vs. -1.86 +/- 0.24). Equal volume of ACSF had no effect on baroreflex sensitivity of pretreated rats (-3.22 +/- 0.31 vs. -2.98 +/- 0.34). These results suggest that ethanol exerts a marked inhibitory action on glutamatergic pathways within the rostral ventrolateral medulla that act to enhance baroreflex sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858, USA.
authors.forename: L
authors.initials: L
authors.lastname: Mao
authors.forename: A A
authors.initials: AA
authors.lastname: Abdel-Rahman
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000008:administration & dosage / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D008845:Microinjections; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
chemical_list: D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D010656:Phenylephrine; D000431:Ethanol; D018698:Glutamic Acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate