The present study was conducted to determine whether atorvastatin reduces hypertension‐induced vascular remodelling and whether its effects involve protein kinase D (PKD) and extracellular signal‐regulated kinase 5 (ERK5). We used 16‐week‐old spontaneously hypertensive rats (SHRs) and age‐matched Wistar‐Kyoto (WKY) rats. The blood pressure and serum lipid concentration were measured. Changes in the vascular morphology and histology were examined using H&E, Masson^’s trichrome, and Sirius Red staining. The media thickness (MT), ratio of MT to lumen diameter (LD) (MT/LD), collagen volume fraction (CVF) and hydroxyproline content were measured to evaluate vascular remodelling. Atorvastatin (50 mg/kg/day) was administered for 8 weeks. Increased blood pressure and vascular remodelling were more prominent in SHRs than in WKY rats. SHRs also had elevated PKD and ERK5 activation. The systolic blood pressure, MT/LD ratio, and hydroxyproline content were positively correlated with the activation level of PKD and ERK5 in SHRs. Atorvastatin significantly attenuated the activation of PKD and ERK5. Overall, this study demonstrated that atorvastatin could reverse vascular remodelling in SHRs. The PKD/ERK5 signalling pathway might be important for elucidating the beneficial pleiotropic effects of atorvastatin on vascular remodelling.

中文翻译：

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阿托伐他汀通过蛋白激酶 D/细胞外信号调节激酶 5 通路减弱自发性高血压大鼠的血管重塑。

本研究旨在确定阿托伐他汀是否减少高血压诱导的血管重塑，以及其作用是否涉及蛋白激酶 D (PKD) 和细胞外信号调节激酶 5 (ERK5)。我们使用了 16 周大的自发性高血压大鼠 (SHR) 和年龄匹配的 Wistar-Kyoto (WKY) 大鼠。测量血压和血脂浓度。使用 H&E, Masson ^'检查血管形态和组织学的变化s 三色和天狼星红染色。测量介质厚度 (MT)、MT 与管腔直径 (LD) 的比率 (MT/LD)、胶原体积分数 (CVF) 和羟脯氨酸含量以评估血管重塑。阿托伐他汀 (50 mg/kg/天) 给药 8 周。与 WKY 大鼠相比，SHR 的血压升高和血管重塑更为突出。SHR 还具有升高的 PKD 和 ERK5 激活。收缩压、MT/LD 比值和羟脯氨酸含量与 SHR 中 PKD 和 ERK5 的激活水平呈正相关。阿托伐他汀显着减弱了 PKD 和 ERK5 的激活。总的来说，这项研究表明阿托伐他汀可以逆转 SHR 的血管重塑。