Park K W, Dai H B, Lowenstein E, Darvish A, Sellke F W
Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Anesth Analg. 1997 Feb;84(2):278-84. doi: 10.1097/00000539-199702000-00008.
Volatile anesthetics attenuate endothelium-dependent vasodilation but the mechanism of attenuation remains controversial. The present study examines the mechanism of isoflurane- and halothane-mediated attenuation of endothelium-dependent vasodilation in Wistar rat coronary microvessels of about 100 microns internal diameter. The vessels were studied in vitro in a pressurized (40 mm Hg), no-flow state using video microscopy. After preconstriction of the vessels with the thromboxane analog U46619 1 microM, concentration response curves to acetylcholine (ACh), the calcium ionophore A23187, sodium nitroprusside (SNP), or the stable cyclic guanosine monophosphate (cGMP) analog 8-bromo-cGMP (Br-cGMP) were obtained in the presence of 0% (control), 1% or 2% isoflurane, or 1% or 2% halothane. Isoflurane 1% and 2% significantly attenuated vasodilation to ACh and A23187. Isoflurane 2%, but not 1%, attenuated vasodilation to SNP. Vasodilation to Br-cGMP was not affected by isoflurane. Halothane attenuated vasodilation to ACh, but had no effect on vasodilation to A23187, SNP, or Br-cGMP. We conclude that isoflurane attenuates endothelium-dependent vasodilation by impairing at least two distinct steps in the nitric oxide (NO)-cGMP pathway, the first being between endothelial increase of calcium and smooth muscle guanylate cyclase and the second being inhibition of soluble guanylate cyclase activity. These two steps appear to have different sensitivities to the effect of isoflurane. Halothane has an effect at the endothelial receptor level, but not any distal steps in the NO-cGMP pathway.
挥发性麻醉剂会减弱内皮依赖性血管舒张，但减弱机制仍存在争议。本研究探讨异氟烷和氟烷介导的内径约100微米的Wistar大鼠冠状动脉微血管内皮依赖性血管舒张减弱的机制。使用视频显微镜在体外对处于加压（40毫米汞柱）、无血流状态的血管进行研究。在用1微摩尔血栓素类似物U46619对血管进行预收缩后，在0%（对照）、1%或2%异氟烷或1%或2%氟烷存在的情况下，获得对乙酰胆碱（ACh）、钙离子载体A23187、硝普钠（SNP）或稳定的环鸟苷单磷酸（cGMP）类似物8-溴-cGMP（Br-cGMP）的浓度反应曲线。1%和2%的异氟烷显著减弱对ACh和A23187的血管舒张。2%而非1%的异氟烷减弱对SNP的血管舒张。对Br-cGMP的血管舒张不受异氟烷影响。氟烷减弱对ACh的血管舒张，但对A23187、SNP或Br-cGMP的血管舒张无影响。我们得出结论，异氟烷通过损害一氧化氮（NO）-cGMP途径中至少两个不同步骤来减弱内皮依赖性血管舒张，第一个步骤在内皮钙增加与平滑肌鸟苷酸环化酶之间，第二个步骤是抑制可溶性鸟苷酸环化酶活性。这两个步骤对异氟烷的作用似乎具有不同的敏感性。氟烷在内皮受体水平起作用，但在NO-cGMP途径的任何远端步骤不起作用。
