Su J Y, Chang Y I, Tang L J
Dept. of Anesthesiology, University of Washington, Seattle 98195.
Anesthesiology. 1994 Sep;81(3):700-9. doi: 10.1097/00000542-199409000-00024.
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.
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.
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.
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.
本研究旨在通过使用离体血管环和去表皮肌条，比较较大直径（主动脉）和较小直径（股动脉）的传导动脉对恩氟烷的血管平滑肌反应，以阐明恩氟烷的作用机制。
用不同浓度的去甲肾上腺素（NE）激活兔主动脉和股动脉的离体完整血管环（内皮剥脱），并在稳态张力下检测恩氟烷的作用。在另一项研究中，血管环在NE激活前用维拉帕米预处理，然后用恩氟烷进行测试。在皂角苷处理的动脉条（“去表皮”）中，使用咖啡因诱导的张力瞬变研究恩氟烷对肌浆网Ca2+摄取或释放的影响。
在离体主动脉环中，恩氟烷（0.9%-5%）在低NE浓度（5和30 nM）时增强张力发展，但在最高浓度（10 μM）时抑制张力发展。相反，恩氟烷在所有NE浓度下均抑制股动脉的张力发展。恩氟烷使经维拉帕米预处理的血管环中NE激活的力量显著增加。在去表皮肌条中，恩氟烷（1%-3%）降低Ca2+摄取（导致50%抑制的浓度：主动脉为1.8%，股动脉为2.5%），并增加肌浆网的Ca2+释放（主动脉为59%-208%，股动脉为10%-55%）。这些作用呈剂量依赖性。恩氟烷增强了ryanodine对咖啡因诱导的张力瞬变的抑制作用。
恩氟烷在主动脉和股动脉中具有相似的作用机制：阻断Ca2+内流，并至少部分地通过ryanodine受体通道引起肌浆网释放Ca2+。恩氟烷的这些细胞作用解释了离体血管环中股动脉张力的抑制和主动脉中NE激活力量的增强。
