The role of nitric oxide in the reversal of hemorrhagic shock by oxotremorine

In the present study, the effect of the nitric oxide synthase inhibitor, N- G-nitro-L-arginine methylester (L-NAME), on the antishock actions of oxotre morine was investigated in rats subjected to hemorrhagic shock under uretha ne anesthesia. L-citrulline production in the AV3V region, as an indicator of nitric oxide (NO) synthesis, was assayed by hi.-h-performance liquid chr omatography (HPLC with fluorescent detection throughout the experiment. The rats were pretreated with either intravenous (i.v.) physiological saline o r L-NAME (2.5 mg/kg) before bleeding. L-NAME potentiated the reversal of hy potension by oxotremorine (25 mug/kg, i.v.). However, oxotremorine either a lone or in combination with L-NAME did not produce any significant change i n 60-min survival rate at this low dose. Analysis of microdialysis samples collected from the AV3V region showed that L-citrulline concentration incre ased during bleeding and that this increase was abolished by L-NAME pretrea tment, These results may suggest that nitric oxide production contributes t o hypotension in rats bled to shock since nitric oxide levels in the AV3V r egion increased in response to bleeding and nitric oxide synthase (NOS) inh ibition abolished this increase and potentiated the oxotremorine-induced re versal of hypotension. (C) 2001 Elsevier Science B.V. All rights reserved.