Berkenboom G, Fang Z Y, Unger P, Goldman M, Fontaine J
Department of Cardiology, Erasmus Hospital, Brussels, Belgium.
Eur J Pharmacol. 1991 Jan 25;193(1):81-6. doi: 10.1016/0014-2999(91)90203-3.
Experiments were performed with isolated rat aortas to study the vasoactive properties of pentoxifylline, a cyclic AMP phosphodiesterase inhibitor, which is used as a hemorheologic agent in the treatment of peripheral vascular disease. In rings precontracted with phenylephrine (0.1 microM), pentoxifylline (10 nM-10 microM) induced concentration-dependent relaxations which were not modified after incubation with indomethacin (3 microM) but which were almost completely abolished after incubation with methylene blue (10 microM) or after mechanical removal of the endothelium. After incubation with pentoxifylline (10 microM) for 30 min, the concentration-response curves for endothelium-dependent relaxations to acetylcholine were shifted to the left and the serotonin-induced contractions were decreased, while the relaxations to forskolin, which are endothelium-independent and cyclic AMP-mediated, were not altered. We conclude that pentoxifylline exerts vasoactive effects that are mediated by endothelium-derived relaxing factor (EDRF), and that pentoxifylline has negligible endothelium-independent vasodilating properties. These properties of inducing or potentiating EDRF-mediated effects might contribute to the efficacy of pentoxifylline in the treatment of vascular disease.
采用离体大鼠主动脉进行实验，以研究己酮可可碱（一种环磷酸腺苷磷酸二酯酶抑制剂，用作血液流变学药物治疗外周血管疾病）的血管活性特性。在苯肾上腺素（0.1微摩尔）预收缩的血管环中，己酮可可碱（10纳摩尔至10微摩尔）诱导浓度依赖性舒张，吲哚美辛（3微摩尔）孵育后该舒张无改变，但亚甲蓝（10微摩尔）孵育后或机械去除内皮后几乎完全消除。己酮可可碱（10微摩尔）孵育30分钟后，内皮依赖性舒张对乙酰胆碱的浓度-反应曲线左移，血清素诱导的收缩减弱，而对福斯可林的舒张（内皮非依赖性且由环磷酸腺苷介导）未改变。我们得出结论，己酮可可碱发挥由内皮源性舒张因子（EDRF）介导的血管活性作用，且己酮可可碱的内皮非依赖性血管舒张特性可忽略不计。诱导或增强EDRF介导作用的这些特性可能有助于己酮可可碱治疗血管疾病的疗效。
