The role of nitric oxide-cGMP system in anesthetic action of volatile anesthetic at spinal cord 7

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 12671461
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: KATOH Takasumi Hamamatsu University School of Medicine, Department of Anesthesiology and Intensive Care, Assistant Professor, 医学部・附属病院, 講師 (80204478)
• Project Period (FY): 2000 – 2001
• Keywords: nitric oxide / sevoflurane / cGMP / spinal cord / 7-nitroindazole / MAC

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>.