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Canadian Journal of Anesthesia, Vol 44, 989-995, Copyright © 1997 by Canadian Anesthesiologists' Society


ARTICLES

Ketamine inhibits nitric oxide synthase in lipopolysaccharide-treated rat alveolar macrophages

CY Li, TC Chou, CS Wong, ST Ho, CC Wu, MH Yen and YA Ding
Department of Anesthesiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China. cyli@ndmcl.ndmctsgh.edu.tw

PURPOSE: To evaluate the effects of ketamine on the activity and protein expression of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide (LPS) in rat alveolar macrophages. METHODS: Pulmonary alveolar macrophages isolated from Wistar-Kyoto rats were used. After incubation of macrophages with ketamine (1, 10, or 100 microM) and LPS (1 microgram.ml-1) for 24 hr, the cell-free medium was removed for measuring the nitrite and tumour necrosis factor-alpha (TNF-alpha) levels by Griess reaction and ELISA kit, respectively. The harvested macrophages were also used to determine the activity of iNOS by using the conversion of [3H]-L-arginine to [3H]-L-citrulline method. In addition, the protein expression of iNOS was detected by Western blot analysis. RESULTS: In rat alveolar macrophages, (i) ketamine (1 to 100 microM) caused a dose-dependent suppression of the production of nitrite and TNF-alpha induced by LPS and (ii) ketamine (100 microM) inhibited the activity (46.5 +/- 4.8%, P < 0.05) and protein expression (35 +/- 11%, P X 0.05) of iNOS in response to LPS. CONCLUSION: These results show that ketamine inhibits the activity and expression of iNOS in LPS-activated alveolar macrophages, which may be associated with the reduction of the release of TNF-alpha following LPS treatment.


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