Department of Pharmaceutical Toxicology, Anadolu University, Eskisehir, Turkey.
Cardiovasc Toxicol. 2012 Mar;12(1):46-55. doi: 10.1007/s12012-011-9137-8.
In our study, we investigated the efficacy of everolimus in combination with sildenafil on hemodynamic and morphological parameters in rats with monocrotaline-induced pulmonary hypertension (PH). Right ventricular pressure (RVP), right ventricular hypertrophy, and the response to vasoconstrictor and vasodilator agents in pulmonary arteries as evaluated by myography and histopathological changes were compared among the groups. RVP and right ventricle/body weight ratios were increased in non-treated monocrotaline groups versus the controls; these increased ratios were decreased in the treated groups and were similar to control values. The contractile responses to endothelin-1 in the pulmonary arteries were decreased in the non-treated monocrotaline groups versus the control. In the treatment groups, contractile responses were similar to those in the controls. Responses to acetylcholine and sodium nitroprusside relaxation were decreased in non-treated monocrotaline groups but were improved significantly in the everolimus groups. Upon histopathological examination, the vascular hypertrophy and cardiac hypertrophy observed in monocrotaline groups were improved by the sildenafil and everolimus treatment. In particular, these improvements became remarkable, including the inflammatory changes, in the everolimus treatment groups. In the light of these results, sildenafil and everolimus in combination were more effective than sildenafil treatment alone in reversing the remodelling process without any cardiovascular toxic effects in the monocrotaline-induced PH model.
在我们的研究中，我们调查了依维莫司联合西地那非对野百合碱诱导的肺动脉高压（PH）大鼠血流动力学和形态学参数的疗效。通过肌动描记法和组织病理学变化比较各组之间右心室压力（RVP）、右心室肥厚以及对血管收缩剂和血管扩张剂的反应。与对照组相比，未治疗的野百合碱组的 RVP 和右心室/体重比增加；在治疗组中，这些增加的比例降低，与对照组相似。与对照组相比，肺动脉内皮素-1的收缩反应在未治疗的野百合碱组中降低。在治疗组中，收缩反应与对照组相似。乙酰胆碱和硝普钠松弛的反应在未治疗的野百合碱组中降低，但在依维莫司组中显著改善。组织病理学检查显示，野百合碱组的血管肥厚和心脏肥厚在西地那非和依维莫司治疗后得到改善。特别是，在依维莫司治疗组中，这些改善包括炎症变化，变得非常显著。鉴于这些结果，与单独使用西地那非相比，依维莫司联合西地那非在逆转野百合碱诱导的 PH 模型重塑过程中更有效，且没有任何心血管毒性作用。
