Blockade of L-glutamate receptors in the rostral ventrolateral medulla contributes to ethanol-evoked impairment of baroreflexes in conscious rats.
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)
Mao
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Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858, USA.
Abdel-Rahman
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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
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