Comparative contractile effects of halothane and sevoflurane in rat aorta.
BACKGROUND
Volatile anesthetic agents have been shown to have contractile effects in vascular tissues during specific conditions. This study compared contractile effects of halothane and sevoflurane in rat aorta treated with verapamil. This study also tried to elucidate the mechanism of the contraction.


METHODS
Endothelium-denuded rat thoracic aorta was used for recording of isometric tension and measurement of influx of 45Ca2+. All experiments were performed in the presence of verapamil. In recording of tension, rings were precontracted with a submaximum dose of phenylephrine, followed by exposure to halothane or sevoflurane. For measurement of influx of 45Ca2+, rat aortic strips were exposed to phenylephrine and then to additional halothane or sevoflurane. Influx of Ca2+ was estimated by incubating the strips in 45Ca2+-labeled solution for 2 min.


RESULTS
Halothane (0.5-4.0%) induced contraction in a dose-dependent manner, whereas sevoflurane (1-4%) had no effect on tension. Influx of 45Ca2+ was strongly enhanced by halothane at 1% and 2%, but only slightly at 4%, and was not affected by 1-4% sevoflurane. SK&F 96365, a blocker of voltage-independent Ca2+ channels, abolished contraction and influx of 45Ca2+ by 1% halothane. Depletion of Ca2+ from the sarcoplasmic reticulum with ryanodine or thapsigargin reduced the contraction induced by halothane at 4% but not that at 1% and 2%.


CONCLUSIONS
Halothane is suggested to cause contraction by enhancing influx of Ca2+ via voltage-independent Ca2+ channels at concentrations up to 2% and by inducing release of Ca2+ at 4%. Sevoflurane (1-4%) is devoid of these contractile effects.
Vinh
V H
VH
Department of Anesthesia, Kyoto University Hospital, Japan.
Enoki
T
T
Hirata
S
S
Toda
H
H
Kakuyama
M
M
Nakamura
K
K
Fukuda
K
K
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004347:Drug Interactions; D006221:Halothane / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane; D014665:Vasodilator Agents / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*
D018685:Anesthetics, Inhalation; D002121:Calcium Channel Blockers; D007093:Imidazoles; D008738:Methyl Ethers; D014665:Vasodilator Agents; D000077149:Sevoflurane; D014700:Verapamil; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium; D006221:Halothane