Glutamate release via NO production evoked by NMDA in the NTS enhances hypotension and bradycardia in vivo.
Nitric oxide (NO) in the nucleus tractus solitarii (NTS) plays an important role in regulating sympathetic nerve activity. The aims of this study were to determine whether the activation of N-methyl-D-aspartate (NMDA) receptors in the NTS facilitates the release of L-glutamate (Glu) via NO production, and, if so, to determine whether this mechanism is involved in the depressor and bradycardic responses evoked by NMDA. We measured the production of NO in the NTS as NO2- and NO3- (NO(x)) or Glu levels by in vivo microdialysis before, during, and after infusion of NMDA in anesthetized rats. We also examined effects of N(omega)-nitro-L-arginine methyl ester (L-NAME) on the changes in these levels. NMDA elicited depressor and bradycardic responses and increased the levels of NO(x) and Glu. L-NAME abolished the increases in the levels of NO(x) and Glu and attenuated cardiovascular responses evoked by NMDA. These results suggest that NMDA receptor activation in the NTS induces Glu release through NO synthesis and that Glu released via NO enhances depressor and bradycardic responses.
Matsuo
I
I
Department of Cardiovascular Medicine, Cardiovascular Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Hirooka
Y
Y
Hironaga
K
K
Eshima
K
K
Shigematsu
H
H
Shihara
M
M
Sakai
K
K
Takeshita
A
A
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001919:Bradycardia / Q000503:physiopathology; D002118:Calcium / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D007022:Hypotension / Q000503:physiopathology; D007263:Infusions, Parenteral; D008297:Male; D017551:Microdialysis; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009573:Nitrites / Q000378:metabolism; D010396:Penicillamine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D026423:S-Nitroso-N-Acetylpenicillamine; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology*
D009566:Nitrates; D020030:Nitric Oxide Donors; D009573:Nitrites; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D018698:Glutamic Acid; D016202:N-Methylaspartate; D026423:S-Nitroso-N-Acetylpenicillamine; D010396:Penicillamine; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester