Involvement of NMDA receptors in the hypotensive response to the injection of L-glutamate into the lateral hypothalamus of unanesthetized rats.
We report that microinjections of L-glutamate (L-glu) or N-methyl-D-aspartic acid (NMDA) in the lateral hypothalamus (LH) of unanesthetized rats caused a hypotensive response. Guide cannulas were stereotaxically placed in the LH 3 days before the experiments, under tribromoethanol anesthesia. One day before the experiments, the femoral artery was cannulated for pulsatile arterial pressure (PAP), mean arterial pressure (MAP) and heart rate (HR) measurements. In the first experiment, unanesthetized rats received microinjections of 2.5, 5.0 or 10.0 nmol/100 nL of L-glu in the LH. Dose-dependent hypotensive responses were observed, without significant concomitant changes in heart rate. In a second group of experiments, 5.0 nmol of L-glu was microinjected into the LH before and 10 min after pretreatment with glutamatergic antagonists. Pretreatments with the non-selective ionotropic glutamatergic-receptor antagonist kynurenic acid or the selective NMDA receptor antagonists AP-7 and LY235959 significantly reduced the hypotensive response to microinjection of L-glu in the LH. Pretreatment with the selective AMPA-receptor antagonist NBQX or with vehicle did not affect the hypotensive response. The present results suggest that the hypotensive response to the injection of L-glu into the LH is mediated by NMDA receptors.
Pajolla
Gisela Pugliesi
GP
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Avenue Bandeirantes 3900, 14040-900, Ribeirão Preto, São Paulo, Brazil.
Pelosi
Gislaine Garcia
GG
Corrêa
Fernando Morgan Aguiar
FM
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000633:toxicity*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism; D007026:Hypothalamic Area, Lateral / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008845:Microinjections / Q000379:methods; D016202:N-Methylaspartate / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D014851:Wakefulness
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate