Blaise G, To Q, Parent M, Lagarde B, Asenjo F, Sauvé R
Department of Anesthesia, University of Montreal, Quebec, Canada.
Anesthesiology. 1994 Feb;80(2):417-26. doi: 10.1097/00000542-199402000-00022.
Halothane attenuates endothelium-dependent relaxation. To differentiate halothane's effect on endothelium-derived relaxing factor/nitric oxide (EDRF/NO) production from its effect on nitric oxide action on vascular smooth muscle, halothane's effect on endothelium-dependent relaxation was studied in a bioassay system.
Indomethacin-treated, bovine aortic endothelial cells (BAEC) grown on microcarrier beads, continuously perfused by oxygenated and carbonated (95% O2, 5% CO2) Krebs-Ringer solution served as nitric oxide donors while an isolated denuded rabbit aortic ring directly superfused by the effluent of the BAEC and precontracted with phenylephrine was used to detect EDRF/NO release. The effect of basal and bradykinin-stimulated EDRF release on the tension of the vascular ring was measured. In the bioassay, it was possible to treat either the vascular denuded ring alone or the vascular ring plus the BAEC with halothane by adding it to the perfusate either upstream or downstream from the BAEC. Halothane (final concentration 2.2%) was added to the perfusate at these two positions, and its effect on the relaxation induced by EDRF/NO was determined. In some experiments, the preparations were treated with hemoglobin or L-monomethyl-L-arginine to attenuate the relaxation induced by the EDRF/NO pathway. Finally, halothane's effect on vascular relaxation induced by an increasing concentration of sodium nitroprusside was measured. Halothane's concentration in the perfusate was determined by gas chromatography using electron capture for anesthetic measurement.
EDRF/NO released by the BAEC was responsible for the relaxation of the vascular ring. Halothane added to the perfusate potentiated the tension induced by phenylephrine (7.1 +/- 1.89%) and attenuated the relaxation induced by the release of EDRF/NO. This effect was reversible after discontinuation of halothane. Halothane's effect was present even when the anesthetic was added to the perfusate downstream to the perfusion of the endothelial cells. Halothane had no effect on the vascular relaxation induced by sodium nitroprusside.
The authors' data demonstrate that halothane does not interfere with endothelial cell release of EDRF/NO and its smooth muscle cell relaxation but seems to modify either EDRF/NO half-life or its activated redox form.
氟烷可减弱内皮依赖性舒张。为区分氟烷对内皮源性舒张因子/一氧化氮（EDRF/NO）生成的影响与其对一氧化氮作用于血管平滑肌的影响，在生物测定系统中研究了氟烷对内皮依赖性舒张的作用。
在微载体珠上培养并用吲哚美辛处理的牛主动脉内皮细胞（BAEC），由含氧和含二氧化碳（95% O₂，5% CO₂）的 Krebs-Ringer 溶液持续灌注，作为一氧化氮供体，而用苯肾上腺素预收缩的离体去内皮兔主动脉环直接由 BAEC 的流出液灌注，用于检测 EDRF/NO 的释放。测量基础和缓激肽刺激的 EDRF 释放对血管环张力的影响。在生物测定中，通过将氟烷添加到 BAEC 上游或下游的灌注液中，可以单独处理血管去内皮环或同时处理血管环和 BAEC。在这两个位置将氟烷（终浓度 2.2%）添加到灌注液中，并确定其对 EDRF/NO 诱导的舒张的影响。在一些实验中，用血红蛋白或 L-单甲基-L-精氨酸处理制剂以减弱 EDRF/NO 途径诱导的舒张。最后，测量氟烷对硝普钠浓度增加诱导的血管舒张的影响。通过使用电子捕获的气相色谱法测定灌注液中氟烷的浓度以进行麻醉剂测量。
BAEC 释放的 EDRF/NO 导致血管环舒张。添加到灌注液中的氟烷增强了苯肾上腺素诱导的张力（7.1±1.89%），并减弱了 EDRF/NO 释放诱导的舒张。停止使用氟烷后，这种作用是可逆的。即使将麻醉剂添加到内皮细胞灌注下游的灌注液中，氟烷的作用仍然存在。氟烷对硝普钠诱导的血管舒张没有影响。
作者的数据表明，氟烷不干扰内皮细胞释放 EDRF/NO 及其对平滑肌细胞的舒张作用，但似乎改变了 EDRF/NO 的半衰期或其活化的氧化还原形式。
