MECHANISMS OF INHIBITION OF ENDOTHELIUM-DEPENDENT RELAXATION BY HALOTHANE, ISOFLURANE, AND SEVOFLURANE

Volatile anaesthetics inhibit endothelium-dependent relaxation, but th e underlying mechanism(s) have not been clarified. In an attempt to el ucidate the mechanism(s), we determined the effects of halothane, isof lurane and sevoflurane on relaxation induced by acetylcholine and sodi um nitro-prusside (SNP) and the cGMP formation elicited by exogenous n itric oxide (NO) and SNP in rat aortas. Acetylcholine (10(-7) - 10(-5) M) - induced relaxation was attenuated by halothane (2%), isoflurane (2%) and sevoflurane (4%). SNP (10(-8) M) - induced relaxation was red uced by halothane (2%), but not by isoflurane (2%) or sevoflurane (4%) . The cGMP level of NO-stimulated aorta was reduced by halothane (2%) and sevoflurane (4%), but not by isoflurane (2%). The cGMP level of SN P (10(-7) M) - stimulated aorta was reduced by halothane (2%) but not by isoflurane (2%) and sevoflurane (4%). We conclude that the mechanis ms responsible for the inhibition of endothelium-dependent relaxation differ among anaesthetics. Isoflurane inhibits the relaxation mainly b y inhibiting the formation of NO in the endothelium. In contrast, the effect of halothane on endothelium-dependent relaxation may be largely due to the inhibition of action of NO in the vascular smooth muscle a nd the effect of sevoflurane may be to inactivate NO or to inhibit the action of NO.