title: Medial prefrontal cortex NMDA receptors and nitric oxide modulate the parasympathetic component of the baroreflex.
abstract: The ventral portion of the medial prefrontal cortex (vMPFC) is involved in the modulation of the parasympathetic component of the baroreflex. In the present study, we verified the effect of blockade of vMPFC glutamatergic receptors and nitric oxide synthases (NOS) on the parasympathetic component of baroreflex in awake rats. Bilateral microinjection of the non-selective ionotropic glutamate antagonist kynurenic acid (KYN) into the vMPFC caused a shift of the threshold of reflex bradycardia toward higher pressures in response to increases in mean arterial pressure (MAP) caused by intravenous infusion of phenylephrine, thus indicating a tonic facilitatory influence action of vMPFC glutamate receptors on the parasympathetic component of the baroreflex. The effect of blockade of vMPFC-NMDA receptors by AP7 was similar to that observed after KYN, suggesting mediation via NMDA receptors. Pretreatment with the NOS inhibitor L-NAME or the specific neural NOS (nNOS) N(omega)-propyl-l-arginine microinjected in the vMPFC caused a shift of the reflex threshold toward higher pressures that was similar to that observed after blockade of NMDA receptors, thus indicating participation of the NO/NMDA-receptor pathway in the vMPFC modulation of the parasympathetic component of the baroreflex. In conclusion, our data indicate that glutamatergic neurotransmission in the vMPFC has a tonic facilitatory influence on the parasympathetic component of the baroreflex. Because local treatment with either the nNOS inhibitor N(omega)-propyl-l-arginine or the specific NMDA antagonist AP7 had similar effects on the baroreflex, it is also suggested that this modulation involves an NMDA-NO interaction within the vMPFC.
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, USP, Av. Bandeirantes 3900, 14049-900 Ribeirão Preto, São Paulo, Brazil.
authors.forename: L B M
authors.initials: LB
authors.lastname: Resstel
authors.forename: F M A
authors.initials: FM
authors.lastname: Corrêa
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D004333:Drug Administration Routes; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D010656:Phenylephrine / Q000008:administration & dosage; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013566:Sympathomimetics / Q000008:administration & dosage; D013997:Time Factors; D014851:Wakefulness
chemical_list: D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; C109116:N(omega)-propargylarginine; D016194:Receptors, N-Methyl-D-Aspartate; D013566:Sympathomimetics; D010656:Phenylephrine; D009569:Nitric Oxide; D015763:2-Amino-5-phosphonovalerate; D001120:Arginine; C031231:2-amino-7-phosphonoheptanoic acid; D019331:NG-Nitroarginine Methyl Ester