PROTECTIVE EFFECT OF NITRIC-OXIDE IN AN ENDOTOXIN-INDUCED SEPTIC SHOCK

BACKGROUND: Calcium ion (Ca++)-independent nitric oxide (NO) synthase activity in animals was markedly induced by treatment with endotoxin, but NO levels in various tissues removed from endotoxin-treated animal s have not been reported. The role of NO during an endotoxin-induced s eptic shock remains controversial. METHODS: ICR mice, randomly divided into one of six treatment groups, received intraperitoneal injections as follows: phosphate-buffered saline; Escherichia coli LPS (LPS); N- omega-nitro-L-arginine (L-NNA); N-omega-nitro-D-arginine (D-NNA); LPS plus L-NNA; and LPS plus D-NNA. The mice were either monitored for mor tality or killed for nitrite/nitrate assays and histologic analysis. R ESULTS: NO revels in many tissues were markedly increased by injection of LPS, and administration of L-NNA increased mortality rates of LPS- treated mice, in association with an increase in tissue damage in the lung, liver, and kidney. CONCLUSIONS: The endogenous NO generated duri ng LPS-mediated septic shock could be protective.