Attenuation of nitric oxide-stimulated soluble guanylyl cyclase from the rat brain by halogenated volatile anesthetics

Purpose. The present study was undertaken to examine whether interaction between halogenated volatile anesthetics and nitric oxide (NO) at soluble guanylyl cyclase (sGC) would occur in rat brain. Methods. A soluble brain fraction was prepared from extensively perfused Sprague-Dawley rat brains by centrifugation and used as the source of sGC. sGC was incubated with NO and halogenated volatile anesthetics, and cGMP production was determined by enzyme immunoassay in aliquots of the supernatant. Results. Halothane and sevoflurane produced significant (P < 0.01) and dose-dependent inhibition of NO-stimulated sGC activity over a range of NO concentrations (2 x 10-9 to 2 x 10(-5) M). Among the anesthetics, halothane tended to have a large inhibitory effect on NO-stimulated sGC activity, which was, however, not significant. sGC activity was also inhibited by both anesthetics (P < 0.05) in the absence of NO stimulation. GTP dose-dependently increased both NO-stimulated and -nonstimulated sGC activities. Halothane and sevoflurane decreased these activities (P < 0.01), but the inhibition by these anesthetics was not significant at higher GTP concentrations. Conclusion. These results suggest that halogenated volatile anesthetics can attenuate the activity of NO-stimulated sGC by competing with NO for the NO binding site on the enzyme.