Lischke V, Busse R, Hecker M
Zentrum der Anästhesie und Wiederbelebung, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1995 Sep;352(3):346-9. doi: 10.1007/BF00168567.
In addition to nitric oxide (NO) and prostacyclin (PGI2) another endothelium-derived factor, which hyperpolarizes vascular smooth muscle cell via activation of K+ channels, contributes to the vasorelaxant effect of bradykinin in different vascular beds. Preliminary findings suggest that this endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilatation is attenuated by both volatile and intravenous anesthetics. Since EDHF may play an important role in the coronary microcirculation, we investigated the effects of isoflurane (2 vol.% equivalent to approximately 250 microM), etomidate (30 and 100 microM), phenobarbital (100 microM) and thiopental (30 and 100 microM) on the EDHF-mediated dilator response to bradykinin and on the endothelium-independent dilatation evoked by sodium nitroprusside (SNP) in the isolated saline-perfused rat heart (Langendorff preparation). None of the anesthetics tested affected the dilator response to bradykinin or SNP under basal conditions. However, following inhibition of NO and PGI2 formation with NG-nitro-L-arginine (100 microM) and diclofenac (1 microM) respectively, isoflurane, etomidate and thiopental, but not phenobarbital, significantly attenuated the NO/PGI2-independent, i.e. EDHF-mediated dilator response to bradykinin, while the vasorelaxant effect of SNP remained unaffected. Isoflurane, etomidate and thiopental, but not phenobarbital, display cytochrome P450-inhibiting properties, suggesting that these anesthetics impair the cytochrome P450-dependent synthesis of EDHF in the coronary microcirculation.
除一氧化氮（NO）和前列环素（PGI2）外，另一种内皮衍生因子可通过激活钾通道使血管平滑肌细胞超极化，它在不同血管床中对缓激肽的血管舒张作用有贡献。初步研究结果表明，这种内皮衍生超极化因子（EDHF）介导的血管舒张作用会被挥发性麻醉药和静脉麻醉药减弱。由于EDHF可能在冠状动脉微循环中起重要作用，我们研究了异氟烷（2体积%，约相当于250微摩尔）、依托咪酯（30和100微摩尔）、苯巴比妥（100微摩尔）和硫喷妥钠（30和100微摩尔）对EDHF介导的缓激肽舒张反应以及对硝普钠（SNP）在离体盐水灌注大鼠心脏（Langendorff标本）中引起的非内皮依赖性舒张的影响。在基础条件下，所测试的麻醉药均未影响对缓激肽或SNP的舒张反应。然而，在用N-硝基-L-精氨酸（100微摩尔）和双氯芬酸（1微摩尔）分别抑制NO和PGI2形成后，异氟烷、依托咪酯和硫喷妥钠（而非苯巴比妥）显著减弱了不依赖NO/PGI2的，即EDHF介导的对缓激肽的舒张反应，而SNP的血管舒张作用未受影响。异氟烷、依托咪酯和硫喷妥钠（而非苯巴比妥）具有细胞色素P450抑制特性，这表明这些麻醉药损害了冠状动脉微循环中细胞色素P450依赖性的EDHF合成。
