Inhibition of glutamate uptake in the rostral ventrolateral medulla enhances baroreflex-mediated bradycardia in conscious rats.
The current investigation tested the hypothesis that inhibition of L-glutamate uptake in the rostral ventrolateral medulla (RVL) enhances the baroreceptor-mediated heart rate responses. In conscious freely moving rats, unilateral microinjection of the L-glutamate uptake blocker p-chloromercuriphenylsalfonic acid (PCMS, 0.1 nmol) elicited a 45% increase in the baroreflex-mediated bradycardic response tested by i.v. phenylephrine (-2.0 +/- 0.1 vs -2.9 +/- 0.2 beats/min/mmHg). In the same rats, evidence for the ability of PCMS to inhibit L-glutamate uptake at the site of its microinjection in the RVL was obtained. PCMS microinjected into the RVL did not influence basal blood pressure and heart rate. However, the cardiovascular responses elicited by L-glutamate (5 nmol) microinjected into the RVL were significantly enhanced by PCMS pretreatment. The pressor and bradycardic responses to L-glutamate increased 53% (from 28.3 +/- 2.4 to 43.4 +/- 4.7 mmHg) and 68% (from -59.6 +/- 13.1 to -100.0 +/- 7.2 beats/min), respectively after PCMS. An equal volume of ACSF microinjected into the RVL had no effect on BRS (-2.1 +/- 0.2 vs -1.9 +/- 0.1 beats/min/mmHg), nor on the pressor (29.9 +/- 7.4 vs 30.6 +/- 4.4 mmHg) and bradycardic (-50.3 +/- 12.0 vs -43.3 +/- 12.0 beats/min) responses elicited by L-glutamate. These findings suggest that: (i) glutamatergic pathways in the RVL serve a facilitatory role in processing the baroreceptor information, and (ii) L-glutamate uptake mechanisms exert a restraining influence on BRS and the cardiovascular effect of L-glutamate.
Mao
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Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858-4353.
Abdel-Rahman
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D002731:4-Chloromercuribenzenesulfonate / Q000494:pharmacology*; D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001692:Biological Transport; D001794:Blood Pressure / Q000187:drug effects; D001931:Brain Mapping; D003243:Consciousness; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D010656:Phenylephrine; D018698:Glutamic Acid; D002731:4-Chloromercuribenzenesulfonate