title: Nitric oxide-dependent guanylyl cyclase participates in the glutamatergic neurotransmission within the rostral ventrolateral medulla of awake rats.
abstract: A well-known action of nitric oxide (NO) is to stimulate the soluble form of guanylyl cyclase, evoking an accumulation of cyclic GMP in target cells. The aim of the present study was to examine the effects of inhibition of guanylyl cyclase dependent on NO during cardiovascular responses induced by L-glutamate and S-nitrosoglutathione (SNOG) microinjected into the rostral ventrolateral medulla (RVLM) of awake rats. Three days before the experiments, adult male Wistar rats (280 to 320 g) were anesthetized for implantation of guide cannulas to the desired stereotaxic position (AP=-2.5 mm, L=1.8 mm) in relation to lambda. The cannulas were fixed to the skull with acrylic cement. Twenty-four hours before the experiments, a femoral artery and vein were cannulated for recording arterial pressure (AP) and heart rate (HR) and injection of anesthetic. Unilateral microinjections (100 nL) of L-glutamate (5 nmol/L) and SNOG (2.5 nmol/L) were made into the histologically confirmed RVLM. The cardiovascular responses to these drugs were evaluated before and after microinjection (3 nmol/L, 200 nL) of either methylene blue or oxodiazoloquinoxaline (ODQ). The hypertensive effect of L-glutamate was attenuated by 74% after methylene blue (DeltaAP=49+/-8 to 13+/-4 mm Hg) and by 80.5% after ODQ (DeltaAP=30+/-2 to 6+/-2 mm Hg). The increase in AP produced by SNOG was fully blocked by ODQ (DeltaAP=39+/-8 to 1+/-2 mm Hg). These data indicate that cyclic GMP mechanisms have a key role in glutamatergic neurotransmission in the RVLM of awake rats, and it is most probable that NO participates in this response.
authors.affiliation: Department of Physiology, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, Brazil.
authors.forename: M C
authors.initials: MC
authors.lastname: Martins-Pinge
authors.forename: G C
authors.initials: GC
authors.lastname: Araújo
authors.forename: O U
authors.initials: OU
authors.lastname: Lopes
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000494:pharmacology / Q000502:physiology*; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000502:physiology*; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D026422:S-Nitrosoglutathione; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D009569:Nitric Oxide; D018698:Glutamic Acid; D026422:S-Nitrosoglutathione; D006162:Guanylate Cyclase; D005978:Glutathione