Mechanisms of inhibition of endothelium-dependent relaxation by halothane, isoflurane, and sevoflurane.
Volatile anaesthetics inhibit endothelium-dependent relaxation, but the underlying mechanism(s) have not been clarified. In an attempt to elucidate the mechanism(s), we determined the effects of halothane, isoflurane and sevoflurane on relaxation induced by acetylcholine and sodium nitroprusside (SNP) and the cGMP formation elicited by exogenous nitric 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 reduced 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 SNP (10(-7) M)-stimulated aorta was reduced by halothane (2%), but not by isoflurane (2%) and sevoflurane (4%). We conclude that the mechanisms responsible for the inhibition of endothelium-dependent relaxation differ among anaesthetics. Isoflurane inhibits the relaxation mainly by 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 and the effect of sevoflurane may be to inactivate NO or to inhibit the action of NO.
Nakamura
K
K
Department of Anesthesia, Kyoto University Hospital, Japan.
Terasako
K
K
Toda
H
H
Miyawaki
I
I
Kakuyama
M
M
Nishiwada
M
M
Hatano
Y
Y
Mori
K
K
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004987:Ethers / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology; D008738:Methyl Ethers; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D000777:Anesthetics; D004987:Ethers; D008738:Methyl Ethers; D009569:Nitric Oxide; D000077149:Sevoflurane; D007530:Isoflurane; D006152:Cyclic GMP; D006221:Halothane