Marshall C, Marshall B E
Department of Anesthesia, University of Pennsylvania School of Medicine, Philadelphia 19104-4283.
Anesthesiology. 1990 Sep;73(3):441-8. doi: 10.1097/00000542-199009000-00012.
Inhalational anesthetics inhibit hypoxic pulmonary vasoconstriction (HPV). One mechanism suggested for this action is stimulation of release of endothelium-derived relaxing factor. The present study has tested this hypothesis. These studies were performed in 66 ventilated and perfused isolated rat lungs. There were three study protocols. Study 1 examined the effect of HPV of the inhibition of soluble guanylate cyclase by methylene blue (MB). In the presence or absence of MB, the lungs constricted to hypoxia with pulmonary artery pressure increases of 8.6 +/- 0.2 cmH2O and 11.5 +/- 0.4 cmH2O, respectively, and halothane, enflurane, and isoflurane caused a reversible 50% decrease in the pulmonary pressor response, but acetylcholine (ACh) was vasodilatory in the saline group and vasoconstrictor in the MB group. In Study II a dose-response curve was established for the potent stimulator (Sin 1) of the enzyme guanylate cyclase. In the presence of MB the dose-response curve for Sin 1 was shifted to the right with an increase in the ED50 for Sin 1 from 44 microM for the control to 85 microM for the MB group. In Study III, baseline pulmonary artery pressure was increased with U46619, and the hypoxic pressor response was increased (28.9 +/- 2.5 cmH2O), but halothane again caused a 50% decrease (11.0 +/- 1.8 cmH2O) in the response to hypoxia. In summary, when soluble guanylate cyclase activity is inhibited by MB, the inhibition of hypoxic pulmonary vasoconstriction by halothane, isoflurane, or enflurane was unaltered, and release of endothelium-derived relaxing factor (EDRF) is therefore not an essential mechanism underlying this action.
吸入性麻醉药可抑制低氧性肺血管收缩（HPV）。针对这一作用提出的一种机制是刺激内皮源性舒张因子的释放。本研究对这一假说进行了验证。这些研究在66个通气和灌注的离体大鼠肺上进行。有三个研究方案。方案1研究了亚甲蓝（MB）抑制可溶性鸟苷酸环化酶对HPV的影响。在有或无MB的情况下，肺脏对低氧产生收缩反应，肺动脉压分别升高8.6±0.2 cmH₂O和11.5±0.4 cmH₂O，氟烷、恩氟烷和异氟烷使肺血管加压反应可逆性降低50%，但乙酰胆碱（ACh）在生理盐水组中是血管舒张剂，而在MB组中是血管收缩剂。在方案II中，为鸟苷酸环化酶的强效刺激剂（Sin 1）建立了剂量-反应曲线。在MB存在的情况下，Sin 1的剂量-反应曲线右移，Sin 1的半数有效剂量（ED50）从对照组的44 μmol增加到MB组的85 μmol。在方案III中，用U46619使基线肺动脉压升高，低氧加压反应增强（28.9±2.5 cmH₂O），但氟烷再次使对低氧的反应降低50%（11.0±1.8 cmH₂O）。总之，当可溶性鸟苷酸环化酶活性被MB抑制时，氟烷、异氟烷或恩氟烷对低氧性肺血管收缩的抑制作用未改变，因此内皮源性舒张因子（EDRF）的释放不是这一作用的必要机制。
