Nitrict Oxide Synthase Inhibitors, 7-Nitro Indazole and Nitro sup G -L-Arginine Methyl Ester, Dose Dependently Reduce the Threshold for Isoflurane Anesthesia

Abstract

Inhibition of the NO synthase pathway decreased the MAC for isoflurane, which suggests that inhibition of the NO pathway decreases the level of consciousness and augments sedation, analgesia, and anesthesia. The MAC reduction by two structurally distinct NO synthase inhibitors supports that this is a specific effect on NO synthase. Furthermore, the action of the neuronal NO synthase inhibitor 7-NI supports an effect selective for neuronal NO synthase and also avoids the hypertensive response of generalized NO synthase inhibitors.

Reduction of isoflurane MAC by fentanyl or remifentanil in rats

“…Intratracheal gas sampling was used to measure anaesthetic gas concentration for determination of the MAC value. This method has been described in detail previously (Pajewski et al. 1996).…”

Is a New Paradigm Needed to Explain How Inhaled Anesthetics Produce Immobility?

“…The neuronal NOS inhibitors L-NAME161–163 or 7-NI160,162,164,165 can decrease MAC by 35%–95%, but not all investigators find an effect of L-NAME on MAC 166,167. Peculiarly, 7-NI decreases MAC to the same extent in wild-type and NOS knockout mice,160 and arginine reverses the effect of the 7-NI by the same amount in wild-type and NOS knockout mice 160.…”

Methylene blue treatment for vasoplegia and resultant isoelectric processed EEG (Bispectral Index)

“…The ability of methylene blue to inhibit the production of NO may provide some insight into its mechanism of action. Nitric oxide is a known neuromodulator with activity in the CNS [26,27]; a reduction in NOS activity decreases MAC [28,29] and propofol requirements [30] in animals. These interactions may be complex, as volatile anesthetics also decrease NOS activity [31].…”