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 ac tion of enflurane by comparing the vascular smooth muscle responses of conduit arteries of larger (aorta) and smaller (femoral artery) diame ter to enflurane using isolated rings and skinned strips. Methods: Iso lated intact rings (endothelium denuded) of aorta and femoral artery f rom rabbits were activated by various concentrations of norepinephrine (NE) and the effects of enflurane were examined at the steady-state f orce. In a separate study, the rings were pretreated with verapamil be fore the NE activation and tested with enflurane. In the saponin-treat ed arterial strips (''skinned''), the effects of enflurane on Ca2+ upt ake or release from the sarcoplasmic reticulum were studied using caff eine-induced tension transients. Results: In isolated aortic rings, en flurane (0.9%-5%) enhanced tension development at low NE concentration s (5 and 30 nM) but depressed it at highest concentration (10 mu M). I n contrast, enflurane depressed tension development in the femoral art ery 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 result ing 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-depende nt. Enflurane potentiated ryanodine depression of caffeine-induced ten sion transients. Conclusions: Enflurane has similar mechanisms of acti on in aorta and femoral artery: blocking Ca2+ influx, and causing, at least in part, Ca2+ release from the sarcoplasmic reticulum through th e ryanodine-receptor channel. These cellular actions of enflurane acco unt for the depression in femoral artery and enhancement in aorta of N E-activated force in isolated rings.