INVOLVEMENT OF NITRIC-OXIDE AND N-METHYL-D-ASPARTATE IN ACUTE HYPOXICALTITUDE CONVULSION IN MICE

Background: Altitude convulsion is a rather specific form of experimen tal convulsion which is induced by acute exposure to a hypobaric hypox ic condition. Several neurotransmitters have been shown to be involved in the mechanisms of altitude convulsions. However, their roles and i nteraction were not clear. Hypothesis: The novel neurotransmitter nitr ic oxide (NO) may be involved in the mechanisms of altitude convulsion through its neuronal signalling roles in relation to the NMDA recepto r. 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 synth esis precursor, L-arginine (20, 40, 200, 800 mg/kg), resulted in a dos e-dependent decrease in the ACT in mice, while the NO synthase (NOS) i nhibitor, N-G-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) p rior 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 mi ce and this decrease in hypoxic tolerance caused by NMDA can be preven ted by pretreatment with either NMDA receptor antagonist 2-amino-5-pho sphovalerate (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 convuls ion and further support the hypothesized relationship between NMDA-rec eptor mediated neurotoxicity and nitric oxide.