Mechanisms of action of enflurane on vascular smooth muscle. Comparison of rabbit aorta and femoral artery.
BACKGROUND
This study was performed to elucidate the mechanisms of action of enflurane by comparing the vascular smooth muscle responses of conduit arteries of larger (aorta) and smaller (femoral artery) diameter to enflurane using isolated rings and skinned strips.


METHODS
Isolated intact rings (endothelium denuded) of aorta and femoral artery from rabbits were activated by various concentrations of norepinephrine (NE) and the effects of enflurane were examined at the steady-state force. In a separate study, the rings were pretreated with verapamil before the NE activation and tested with enflurane. In the saponin-treated arterial strips ("skinned"), the effects of enflurane on Ca2+ uptake or release from the sarcoplasmic reticulum were studied using caffeine-induced tension transients.


RESULTS
In isolated aortic rings, enflurane (0.9%-5%) enhanced tension development at low NE concentrations (5 and 30 nM) but depressed it at highest concentration (10 microM). In contrast, enflurane depressed tension development in the femoral artery at all NE concentrations. Enflurane caused significant increase in the NE-activated force in rings pretreated with verapamil. In skinned strips, enflurane (1%-3%) decreased Ca2+ uptake (concentration resulting in 50% depression: 1.8% for aorta and 2.5% for femoral artery) and increased Ca2+ release from the sarcoplasmic reticulum (59%-208% for aorta and 10%-55% for femoral artery). These effects were dose-dependent. Enflurane potentiated ryanodine depression of caffeine-induced tension transients.


CONCLUSIONS
Enflurane has similar mechanisms of action in aorta and femoral artery: blocking Ca2+ influx, and causing, at least in part, Ca2+ release from the sarcoplasmic reticulum through the ryanodine-receptor channel. These cellular actions of enflurane account for the depression in femoral artery and enhancement in aorta of NE-activated force in isolated rings.
Su
J Y
JY
Dept. of Anesthesiology, University of Washington, Seattle 98195.
Chang
Y I
YI
Tang
L J
LJ
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000493:pharmacokinetics / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004737:Enflurane / Q000494:pharmacology*; D005263:Femoral Artery / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D012433:Ryanodine; D002110:Caffeine; D004737:Enflurane; D014700:Verapamil; D002118:Calcium; D009638:Norepinephrine