Involvement of nitric oxide production via kynurenic acid-sensitive glutamate receptors in DOPA-induced depressor responses in the nucleus tractus solitarii of anesthetized rats.
We have proposed the hypothesis that L-3,4-dihydroxyphenylalanine (DOPA) plays a role of neurotransmitter of the primary baroreceptor afferents terminating in the nucleus tractus solitarii (NTS). In the present study, we tried to clarify whether glutamate receptors and/or nitric oxide (NO), important modulators for central cardiovascular regulation, are involved in the DOPA-induced cardiovascular responses in the nucleus. Male Wistar rats were anesthetized with urethane and artificially ventilated. Compounds or antisense oligos (17-mer) for neuronal NO synthase were microinjected into depressor sites of the unilateral nucleus. DOPA 30-300 pmol microinjected into the nucleus dose-dependently induced depressor and bradycardic responses. Prior injection of kynurenic acid (600 pmol) suppressed DOPA (300 pmol)-induced responses by approximately 80%. Prior injection of N(G)-monomethyl-L-arginine 100 nmol, a potent NO synthase inhibitor, reversibly attenuated by approximately 90% DOPA-induced responses, while the D-isomer 100 nmol produced no effect. Furthermore, prior injection of neuronal NO synthase antisense oligos (20 pmol) reversibly reduced by approximately 70% responses to DOPA. Sense or scrambled oligos produced no effect. A NO precursor L-arginine (30 nmol) induced depressor and bradycardic responses, but these responses were not affected by kynurenic acid. These results suggest important roles for glutamate receptors and NO in DOPA induced-depressor and bradycardic responses in the NTS.
Yamanashi
Kaori
K
Department of Pharmacology, Yokohama City University School of Medicine, Japan.
Miyamae
Takeaki
T
Sasaki
Yukio
Y
Maeda
Masanobu
M
Hirano
Hideyasu
H
Misu
Yoshimi
Y
Goshima
Yoshio
Y
D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000494:pharmacology*; D007736:Kynurenic Acid / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000378:metabolism*; D017552:Solitary Nucleus / Q000187:drug effects* / Q000378:metabolism
D018686:Anesthetics, Intravenous; D017470:Receptors, Glutamate; D009569:Nitric Oxide; D004295:Dihydroxyphenylalanine; D007736:Kynurenic Acid