Mechanisms of action of isoflurane on contraction of rabbit conduit artery.
Isoflurane may cause differential effects on different vascular beds of the same animal species. The mechanisms of this action have not been elucidated. Accordingly, we compared in rabbit aorta and femoral artery the effects of isoflurane (1-3.3%) in isolated rings (endothelium denuded) activated by norepinephrine, and isoflurane effects on Ca2+ fluxes from the sarcoplasmic reticulum in skinned strips. When < 30 nM norepinephrine was used to cause ring contraction, isoflurane increased the force of contraction in aortic rings, but decreased force in femoral arterial rings. At 30 nM norepinephrine stimulation, 3.3% isoflurane decreased the force and, in the presence of verapamil, isoflurane actually increased the force in both arterial types. In skinned strips of both arterial types, isoflurane present during Ca2+ uptake decreased the caffeine-induced tension transients, whereas isoflurane present during Ca2+ release enhanced the transients. Isoflurane potentiated the depression of the tension transients by ryanodine. Isoflurane directly caused contracture even in the absence of caffeine. Thus, isoflurane has similar cellular mechanisms of action in the aortic and femoral arterial smooth muscle: inhibiting Ca2+ influx through the sarcolemma, decreasing Ca2+ uptake by the sarcoplasmic reticulum, and enhancing caffeine-induced Ca2+ release from the sarcoplasmic reticulum.
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J Y
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Department of Anesthesiology, University of Washington, Seattle 98195-6540, USA.
D000818:Animals; D001011:Aorta / Q000187:drug effects*; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology; D005263:Femoral Artery / Q000187:drug effects*; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D002110:Caffeine; D014700:Verapamil; D007530:Isoflurane; D002118:Calcium; D009638:Norepinephrine