| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Background and objective The purpose of this study was to determine the effect of acute and chronic administration of 7-nitroindazole, a selective neuronal nitric oxide synthase inhibitor, on the righting reflex ED_<50> and minimum alveolar concentration during sevoflurane anaesthesia in rats.
Methods Seven-nitroindazole was acutely (0, 50, and 100 mg kg^<-1>) and chronically (0 and 150 mg kg^<-1> day^<-1>, 4 days) administered to rats. After the preparation, minimum alveolar concentration and righting reflex ED_<50> was measured. The concentration of cyclic GMP in the brain, cerebellum and spinal cord was also measured.
Results Acute administration reduced the minimum alveolar concentration (50 mg kg^<-1>, 58.8 % (95 %CI 50.3-67.3 %) of the baseline value, P<0.01; 100 mg kg^<-1>, 55.8 (46.9-64.7), P<0.01) and the righting reflex ED_<50> (50 mg kg^<-1>, 27.2 (17.2-37.2), P<0.01; 100 mg kg^<-1>, 14.3 (6.6-22.0), P<0.01). Chronic administration did not reduce the minimum alveolar concentration, however, it reduced the righting reflex ED_<50> (65.3 (52.9-77.7), P<0.01). Overall, the reduction in minimum alveolar concentration in acute and chronic protocol did not correlate with that of the righting reflex ED_<50>. Seven-nitroindazole (100 mg kg^<-1>, acute) reduced the cyclic GMP level within the cerebellum by 55.4 %, however, it did not decrease levels in the brain or spinal cord.
Conclusions Different mechanisms are responsible for the observed alterations in minimum alveolar concentration and righting reflex ED_<50> following treatment with 7-nitroindazole. The nitric oxide - cyclic GMP pathway might play a less important role in the determination of minimum alveolar concentration than the righting reflex ED_<50>.
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