a Fujian Hypertension Research Institute, First Affiliated Hospital of Fujian Medical University , Fuzhou , PR China.
Clin Exp Hypertens. 2017;39(6):495-501. doi: 10.1080/10641963.2016.1254225. Epub 2017 Jun 19.
This study examined the effects of preventive atorvastatin (Ator) treatment on vasodilatation of small pulmonary arteries (SPAs) in monocrotaline (MCT)-induced pulmonary hypertensive rats. SD rats were randomly assigned to: normal control (Ctr), pulmonary arterial hypertension (PAH), PAH treated with 5 mg/kg/d Ator (LAtor), or 10 mg/kg/d Ator (HAtor). PAH was induced by MCT injection (40 mg/kg, i.p.). Mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI%), endothelium-dependent relaxations (EDdRs), and endothelium-independent relaxations (EDiRs) were determined. Four weeks after MCT injection, mPAP was higher in PAH group compared to that in Ctr group, and this effect was suppressed by Ator treatment (PAH: 32.19 ± 0.91 mm Hg vs. LAtor: 19.13 ± 1.01 mm Hg, HAtor: 17.55 ± 0.20 mm Hg, p < 0.05). Similar trend of changes in RVHI% was found in the same way. EDdRs of SPA rings in PAH group were markedly decreased 2 and 4 weeks after MCT injection, while in Ator treated groups, the impairment can only be detected 4 weeks after MCT injection. There were no differences in EDiRs among all groups 1 week after MCT injection. However, 2 weeks and 4 weeks after MCT injection, EDiRs were significantly impaired, while in HAtor and LAtor groups, EDiR was only impaired 4 weeks but not 2 weeks after MCT injection. Preventive treatment with atorvastatin for 2 weeks ameliorated endothelium-dependent and endothelium-independent vasodilative dysfunction in small pulmonary artery rings of MCT-induced PAH rats. It suggests that MCT-induced damage of endothelial function was progressing, and Ator was only beneficial in the early stage of MCT-induced PAH.
本研究旨在探讨预防性阿托伐他汀（Ator）治疗对野百合碱（MCT）诱导肺动脉高压大鼠的小肺动脉（SPAs）舒张功能的影响。SD 大鼠随机分为：正常对照组（Ctr）、肺动脉高压组（PAH）、5mg/kg/d Ator 治疗组（LAtor）和 10mg/kg/d Ator 治疗组（HAtor）。通过 MCT 注射（40mg/kg，腹腔内）诱导 PAH。测定平均肺动脉压（mPAP）、右心室肥厚指数（RVHI%）、内皮依赖性舒张（EDdR）和内皮非依赖性舒张（EDiR）。MCT 注射后 4 周，PAH 组 mPAP 高于 Ctr 组，阿托伐他汀治疗抑制了这种作用（PAH：32.19±0.91mmHg vs. LAtor：19.13±1.01mmHg，HAtor：17.55±0.20mmHg，p<0.05）。RVHI%的变化趋势也相似。PAH 组 SPA 环的 EDdR 在 MCT 注射后 2 周和 4 周明显降低，而在阿托伐他汀治疗组，仅在 MCT 注射后 4 周才能检测到损伤。MCT 注射后 1 周，各组之间 EDiR 无差异。然而，2 周和 4 周后，EDiR 明显受损，而在 HAtor 和 LAtor 组，仅在 MCT 注射后 4 周而不是 2 周后 EDiR 受损。阿托伐他汀预防性治疗 2 周可改善野百合碱诱导肺动脉高压大鼠小肺动脉环的内皮依赖性和非内皮依赖性血管舒张功能障碍。这表明 MCT 诱导的内皮功能损伤在进展，阿托伐他汀仅在 MCT 诱导的 PAH 早期有益。
