Selective sensitization by L-glutamate of baroreflex-mediated bradycardia following microinjection into the rostral ventrolateral medulla.
This study examined the role of L-glutamate receptors in different sites in the rostral ventrolateral medulla (RVL) on baseline mean arterial pressure (MAP), heart rate (HR), sympathetic efferent discharge (SED) as well as baroreflex control of HR and SED. Depending on the site, the hemodynamic responses varied from an increase to a decrease in MAP which was accompanied by a similar or an opposite change in HR; the change in SED correlated positively with the change in MAP. Because injection of the test dose of glutamate (5 nM) into the deepest portion of the RVL produced the most pronounced increases in MAP, which was accompanied by a brisk bradycardia, we decided to investigate the nature of these responses. Dose-related sympathoexcitatory, pressor and bradycardic effects were obtained in response to 1, 3, 5 and 10 nM glutamate. The glutamate antagonist, glutamate diethylester (GDEE) abolished these responses and decreased baseline MAP, HR and SED. That glutamate-evoked bradycardia was baroreceptor-mediated was supported by: (1) the bradycardia was not only eliminated but was also converted to a small but significant tachycardic response in sinoaortic denervated rats and following cardiac muscarinic blockade; (2) glutamate substantially sensitized the baroreceptor HR and had no effect on SED response when tested by phenylephrine; and (3) GDEE abolished the sensitizing action of glutamate on the baroreflex control of HR. We conclude that glutamatergic pathways in the deepest portion of the RVL are tonically active and subserve sympathoexcitatory, pressor and tachycardic effects. Also, glutamate differentially sensitizes the baroreceptor reflex pathways that control HR by mainly activating the vagal component of the reflex, an effect which masks its tachycardic effect.
Zhang
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X
Department of Pharmacology, East Carolina University, School of Medicine, Greenville, NC 27858.
Abdel-Rahman
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AA
Wooles
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WR
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005971:Glutamates / Q000008:administration & dosage / Q000494:pharmacology*; D018698:Glutamic Acid; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D010656:Phenylephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013238:Stereotaxic Techniques; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology
D005971:Glutamates; D010656:Phenylephrine; D018698:Glutamic Acid