Halothane and enflurane constrict canine mesenteric arteries by releasing Ca2+ from intracellular Ca2+ stores.
BACKGROUND
Recent studies suggest that volatile anesthetics cause not only vasodilation but also vasoconstriction, depending on the experimental conditions. However, the mechanism of the constrictive effect of volatile anesthetics has not been clarified. The aim of this study was to evaluate the vasoconstrictor effects of halothane, enflurane, and isoflurane and to elucidate the underlying mechanism.


METHODS
Vascular rings of canine mesenteric arteries were mounted in organ baths, and isometric tension changes were recorded. Changes in intracellular free Ca2+ concentration of vascular smooth muscle were examined by using the fluorescent Ca2+ indicator fura 2 and a dual-wavelength fluorometer.


RESULTS
Halothane (0.75-2.3%) and enflurane (1.7-3.4%), but not isoflurane (1.2-3.5%), induced a concentration-dependent transient contraction, followed by a slight, sustained contraction. Halothane (1.5%)- and enflurane (3.4%)-induced contractions were reduced by endothelial denudation and enhanced by indomethacin (10(-5) M) treatment but were not affected by L-NG-nitroarginine (10(-5) M) or nifedipine (2 x 10(-7) M) treatment. Ryanodine (2 x 10(-5) M) treatment completely abolished the transient increases in tension and Ca2+ concentration. Even in ryanodine-treated arteries, however, both anesthetics induced a slowly developing sustained contraction, and the sustained contraction induced by enflurane (3.4%) was not accompanied by a significant increase in Ca2+ concentration.


CONCLUSIONS
Halothane and enflurane, but not isoflurane, induce vasoconstriction by releasing Ca2+ from intracellular stores. Release of a vasodilating prostanoid and endothelium-derived constricting factor may also be involved in the vasoconstrictor effect. Furthermore, increased Ca2+ sensitivity of contractile machinery may be involved in the effect of enflurane.
Kakuyama
M
M
Department of Anesthesia, Kyoto University Hospital, Japan.
Hatano
Y
Y
Nakamura
K
K
Toda
H
H
Terasako
K
K
Nishiwada
M
M
Mori
K
K
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D004285:Dogs; D004737:Enflurane / Q000494:pharmacology*; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives; D006221:Halothane / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D019335:Nitroarginine; D012433:Ryanodine / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D005456:Fluorescent Dyes; C049925:fura-2-am; D012433:Ryanodine; D019335:Nitroarginine; D002110:Caffeine; D004737:Enflurane; D001120:Arginine; D009543:Nifedipine; D002118:Calcium; D016257:Fura-2; D006221:Halothane; D007213:Indomethacin