Involvement of nitric oxide and N-methyl-D-aspartate in acute hypoxic altitude convulsion in mice.
BACKGROUND
Altitude convulsion is a rather specific form of experimental convulsion which is induced by acute exposure to a hypobaric hypoxic condition. Several neurotransmitters have been shown to be involved in the mechanisms of altitude convulsions. However, their roles and interaction were not clear.


OBJECTIVE
The novel neurotransmitter nitric oxide (NO) may be involved in the mechanisms of altitude convulsion through its neuronal signalling roles in relation to the NMDA receptor.


METHODS
There were 177 mice intraperitoneally administrated (i.p.) with several drugs. The altitude convulsion threshold (ACT) was used as an index to evaluate the acute hypoxic tolerance.


RESULTS
NO synthesis precursor, L-arginine (20, 40, 200, 800 mg/kg), resulted in a dose-dependent decrease in the ACT in mice, while the NO synthase (NOS) inhibitor, NG-nitro-L-arginine-methyl ester (L-NAME, 1.25, 2.50, 5.00 mg/kg, i.p.) increased the ACT. Pretreatment with L-NAME (5.0 mg/kg) prior to L-arginine (200 mg/kg) administration prevented the effect of decreasing ACT caused by L-arginine. Similarly, N-methyl-D-aspartate (NMDA, 2.5, 10.0, 20.0 mg/kg, i.p.) yielded a decrease in the ACT in mice and this decrease in hypoxic tolerance caused by NMDA can be prevented by pretreatment with either NMDA receptor antagonist 2-amino-5-phosphovalerate (AP-5, 20.0 mg/kg, i.p.) or NOS inhibitor L-NAME (5.0 mg/kg, i.p.).


CONCLUSIONS
These findings suggest an important signalling role for nitric oxide and NMDA in the development of altitude convulsion and further support the hypothesized relationship between NMDA-receptor mediated neurotoxicity and nitric oxide.
Chen
C H
CH
Department of Physiology, Taipei Medical College, Taiwan.
Chen
A C
AC
Liu
H J
HJ
D000208:Acute Disease; D000532:Altitude Sickness / Q000150:complications*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016202:N-Methylaspartate / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D012640:Seizures / Q000209:etiology* / Q000378:metabolism*; D012720:Severity of Illness Index; D015398:Signal Transduction; D013997:Time Factors
D009569:Nitric Oxide; D016202:N-Methylaspartate