Nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, increases the anaesthetic potency of etomidate.

Objective: Comparable to other intravenous anaesthetics, etomidate is thought to mediate its anaesthetic effect through an action on gamma-amino-butyric-acid (GABA) receptors. Recently, there is evidence that general anaesthetics act on second messenger systems such as the nitric oxide (NO) metabolism too. This study was designed to evaluate the effects of the NO-synthase inhibitor nitro-l-arginine methyl ester (L-NAME) on the anaesthetic potency of the intravenous anaesthetic etomidate. Methods: With approval of the local animal care committee, the effect of L-NAME on the anaesthetic potency of etomidate was studied in Xenopus laevis tadpoles. The animals were exposed to different concentrations of the anaesthetic etomidate or a combination of etomidate and 1 mM L-NAME for 120 min. Anaesthesia was defined as loss of righting reflex for more than 5 s. A concentration-response curve was Fitted to the data according to the method of Waud for quantal biological data and half maximal effects (EC50) and slopes of the curves were calculated. Results: In both groups, the fraction of anaesthetised animals increased with increasing etomidate concentrations. The calculated values were EC50 4.5 +/- 0.2 mu M in the etomidate group with a slope of 2.6 +/- 0.3 (mean +/- SE). The etomidate plus L-NAME group exhibited a significantly different EC50 of 3.0 +/- 0.2 mu M with a slope of 2.3 +/- 0.3. Conclusion: The NO-metabolism has been suggested to be involved in the anaesthetic action of volatile as well as intravenous anaesthetics. The reduction in EC50 of etomidate in presence of L-NAME is comparable to that observed for thiopental or halothane, and thus may indicate an additional mechanism of action of etomidate.