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Role of N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors in the cardiovascular effects of L-glutamate microinjection into the hypothalamic paraventricular nucleus of unanesthetized rats.

Abstract
We report on the cardiovascular effects of L-glutamate (L-glu) microinjection into the hypothalamic paraventricular nucleus (PVN) as well as the mechanisms involved in their mediation. L-glu microinjection into the PVN caused dose-related pressor and tachycardiac responses in unanesthetized rats. These responses were blocked by intravenous (i.v.) pretreatment with the ganglion blocker pentolinium (PE; 5 mg/kg), suggesting sympathetic mediation. Responses to L-glu were not affected by local microinjection of the selective non-NMDA receptor antagonist NBQX (2 nmol) or by local microinjection of the selective NMDA receptor antagonist LY235959 (LY; 2 nmol). However, the tachycardiac response was changed to a bradycardiac response after treatment with LY235959, suggesting that NMDA receptors are involved in the L-glu heart rate response. Local pretreatment with LY235959 associated with systemic PE or dTyr(CH(2))(5)(Me)AVP (50 microg/kg) respectively potentiated or blocked the response to L-glu, suggesting that L-glu responses observed after LY235959 are vasopressin mediated. The increased pressor and bradycardiac responses observed after LY + PE was blocked by subsequent i.v. treatment with the V(1)-vasopressin receptor antagonist dTyr(CH(2))(5)(Me)AVP, suggesting vasopressin mediation. The pressor and bradycardiac response to L-glu microinjection into the PVN observed in animals pretreated with LY + PE was progressively inhibited and even blocked by additional pretreatment with increasing doses of NBQX (2, 10, and 20 nmol) microinjected into the PVN, suggesting its mediation by local non-NMDA receptors. In conclusion, results suggest the existence of two glutamatergic pressor pathways in the PVN: one sympathetic pathway that is mediated by NMDA receptors and a vasopressinergic pathway that is mediated by non-NMDA receptors.
AuthorsCristiane Busnardo, Rodrigo F Tavares, Fernando M A Corrêa
JournalJournal of neuroscience research (J Neurosci Res) Vol. 87 Issue 9 Pg. 2066-77 (Jul 2009) ISSN: 1097-4547 [Electronic] United States
PMID19229989 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright(c) 2009 Wiley-Liss, Inc.
Chemical References
  • Excitatory Amino Acid Antagonists
  • Ganglionic Blockers
  • Receptors, N-Methyl-D-Aspartate
  • Arginine Vasopressin
  • Glutamic Acid
Topics
  • Animals
  • Arginine Vasopressin (analogs & derivatives, metabolism, pharmacology)
  • Autonomic Pathways (drug effects, metabolism)
  • Blood Pressure (drug effects, physiology)
  • Cardiovascular Physiological Phenomena (drug effects)
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists (pharmacology)
  • Ganglionic Blockers (pharmacology)
  • Glutamic Acid (metabolism, pharmacology)
  • Heart Rate (drug effects, physiology)
  • Male
  • Microinjections
  • Neurons (drug effects, metabolism)
  • Paraventricular Hypothalamic Nucleus (drug effects, metabolism)
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate (drug effects, metabolism)
  • Sympathetic Nervous System (drug effects, metabolism)

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