Abstract
Previous reports have described that glutamate ionotropic receptors in the nucleus tractus solitarius (NTS) are involved in the reflex control of heart rate, and that such a control can be inhibited by NTS-5-HT(3) receptor stimulation. In the present study, we examined in urethane anaesthetized rats the effects of intra-NTS microinjection of 1-(m-chlorophenyl)-biguanide (CPBG), a potent and selective 5-HT(3) receptor agonist, on the cardiovascular responses to local administration of glutamate ionotropic receptor agonists. Intra-NTS microinjection of CPBG reduced the atropine-sensitive bradycardia elicited by local microinjection of NMDA without affecting the cardiovascular responses to intra-NTS microinjections of AMPA or kainic acid. The reduction by CPBG of the NMDA-evoked cardiac response was blocked by prior intra-NTS microinjection of granisetron, a 5-HT(3) receptor antagonist, as well as bicuculline, a GABA(A) receptor antagonist. These results suggest that the stimulation of NTS 5-HT(3) receptors specifically reduces, via a GABA-dependent mechanism, the cardiac response to local NMDA administration.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Baroreflex / drug effects
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Bicuculline / pharmacology
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Biguanides / pharmacology
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Excitatory Amino Acid Agonists / administration & dosage
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Excitatory Amino Acid Agonists / pharmacology*
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GABA Antagonists / pharmacology
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Granisetron / pharmacology
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Heart Rate / drug effects*
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Hemodynamics / drug effects
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Male
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Microinjections
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N-Methylaspartate / administration & dosage
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N-Methylaspartate / pharmacology*
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Rats
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Rats, Sprague-Dawley
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Receptors, Kainic Acid / antagonists & inhibitors
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Receptors, Serotonin / drug effects*
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Receptors, Serotonin, 5-HT3
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Serotonin Antagonists / pharmacology
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Serotonin Receptor Agonists / pharmacology
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Solitary Nucleus / physiology*
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Sympathetic Nervous System / drug effects
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology
Substances
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Biguanides
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Excitatory Amino Acid Agonists
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GABA Antagonists
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Receptors, Kainic Acid
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Receptors, Serotonin
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Receptors, Serotonin, 5-HT3
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Serotonin Antagonists
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Serotonin Receptor Agonists
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N-Methylaspartate
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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1-(3-chlorophenyl)biguanide
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Granisetron
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Bicuculline