去氢异雄酮衍生物对离体大鼠心脏模型的正性肌力作用。

Laboratory of Pharmaco-Chemistry at the Faculty of Chemical Biological Sciences of the University Autonomic of Campeche, Av. Agustín Melgar s/n, C.P. 24039, Col. Buenavista, CAM, Mexico,

Arch Pharm Res. 2013 Oct;36(10):1270-8. doi: 10.1007/s12272-013-0166-7. Epub 2013 Jul 4.

Experimental studies indicate that some steroid derivatives have inotropic activity; nevertheless, there is scarce information about the effects of the dehydroisoandrosterone and its derivatives at cardiovascular level. In addition, to date the cellular site and mechanism of action of dehydroisoandrosterone at cardiovascular level is very confusing. In order, to clarify those phenomena in this study, a dehydroisoandrosterone derivative was synthesized with the objective of to evaluate its activity on perfusion pressure and coronary resistance and compare this phenomenon with the effect exerted by dehydroisoandrosterone. The Langendorff technique was used to measure changes on perfusion pressure and coronary resistance in an isolated rat heart model in absence or presence of dehydroisoandrosterone and its derivative. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by dehydroisoandrosterone derivative was evaluated by measuring left ventricular pressure in absence or presence of following compounds; flutamide, prazosin, metoprolol and nifedipine. The results showed that dehydroisoandrosterone derivative significantly increased the perfusion pressure and coronary resistance in comparison with the control conditions and dehydroisoandrosterone. Additionally, other data indicate that dehydroisoandrosterone derivative increase left ventricular pressure in a dose-dependent manner [1 × 10(-9)-1 × 10(-4) mmol]; nevertheless, this phenomenon was significantly inhibited by nifedipine at a dose of 1 × 10(-6) mmol. In conclusion, these data suggest that dehydroisoandrosterone derivative induces positive inotropic activity through of activation the L-type calcium channel.

实验研究表明，一些甾体衍生物具有变力活性；然而，关于脱氢异雄酮及其衍生物在心血管水平的影响的信息却很少。此外，迄今为止，脱氢异雄酮在心血管水平的细胞作用部位和作用机制仍非常混乱。为了澄清这些现象，本研究合成了一种脱氢异雄酮衍生物，旨在评估其对灌流压和冠状动脉阻力的活性，并将这种现象与脱氢异雄酮的作用进行比较。采用 Langendorff 技术测量了在缺乏或存在脱氢异雄酮及其衍生物的情况下，分离大鼠心脏模型中灌流压和冠状动脉阻力的变化。此外，通过测量左心室压力，评估了参与脱氢异雄酮衍生物变力活性的分子机制，方法是在存在或不存在以下化合物的情况下进行：氟他胺、哌唑嗪、美托洛尔和硝苯地平。结果表明，与对照条件和脱氢异雄酮相比，脱氢异雄酮衍生物显著增加了灌流压和冠状动脉阻力。此外，其他数据表明，脱氢异雄酮衍生物以剂量依赖的方式增加左心室压力[1×10(-9)-1×10(-4)mmol]；然而，这种现象在 1×10(-6)mmol 时被硝苯地平显著抑制。综上所述，这些数据表明，脱氢异雄酮衍生物通过激活 L 型钙通道诱导正性变力活性。