a Department of Cardiology , Zhujiang Hospital Affiliated to Southern Medical University , Guangzhou , Guangdong Province , P.R. China.
b Department of Cardiology , The First Hospital of Nanping , Nanping , Fujian Province , P.R. China.
Clin Exp Hypertens. 2018;40(1):39-48. doi: 10.1080/10641963.2017.1299746. Epub 2017 Oct 26.
Increased short-term blood pressure variability (BPV) is strongly correlated with target organ damage. However, the molecular mechanisms underlying abnormal BPV-induced organ damage and effective therapeutic targets are poorly understood. The purpose of this study was to investigate the effects of losartan on vasomotor function and canonical transient receptor potential (TRPC) channels in the aortas of rats with arterial pressure lability induced by sinoaortic denervation (SAD). SAD was performed in male Sprague-Dawley rats at the age of 10 weeks. The experiment included sham-operated (Sham), SAD, and losartan-treated SAD (SAD+Los) groups. After 8 weeks of treatment, hemodynamic parameters were measured via catheterization, thoracic aortic vasomotor functions were evaluated using a physiological vascular ring tension recording system, and TRPC1 and 6 mRNA and protein expression levels in the endothelial cells (ECs) and smooth muscle cells (SMCs) of the thoracic aorta were determined via reverse transcription polymerase chain reaction (RT-PCR) and Western-blotting, respectively. Compared with Sham rats, SAD rats exhibited significantly increased BPV, enhanced norepinephrine-induced aortic contraction, and attenuated acetylcholine-induced aortic relaxation. Both the mRNA and the protein expression levels of TRPC1 and 6 were significantly downregulated in the ECs and upregulated in the SMCs of the thoracic aortas of SAD rats. Losartan treatment prevented these SAD-induced changes. In conclusion, losartan efficiently prevented vasomotor function impairment in SAD rats by reducing BPV and regulating TRPC1 and 6 expression levels.
短期血压变异性（BPV）增加与靶器官损伤密切相关。然而，异常 BPV 诱导的器官损伤的分子机制和有效的治疗靶点仍知之甚少。本研究旨在探讨 losartan 对去窦神经（SAD）诱导的血压波动性大鼠主动脉血管舒缩功能和经典瞬时受体电位（TRPC）通道的影响。在 10 周龄雄性 Sprague-Dawley 大鼠中进行 SAD。实验包括假手术（Sham）、SAD 和 losartan 治疗的 SAD（SAD+Los）组。治疗 8 周后，通过导管测量血流动力学参数，使用生理血管环张力记录系统评估胸主动脉血管舒缩功能，通过逆转录聚合酶链反应（RT-PCR）和 Western-blotting 分别检测胸主动脉内皮细胞（EC）和平滑肌细胞（SMC）中 TRPC1 和 6 mRNA 和蛋白表达水平。与 Sham 大鼠相比，SAD 大鼠的 BPV 显著增加，去甲肾上腺素诱导的主动脉收缩增强，乙酰胆碱诱导的主动脉舒张减弱。SAD 大鼠胸主动脉 EC 中 TRPC1 和 6 的 mRNA 和蛋白表达水平均显著下调，SMC 中表达水平显著上调。Losartan 治疗可预防这些 SAD 诱导的变化。结论：Losartan 通过降低 BPV 和调节 TRPC1 和 6 的表达水平，有效预防 SAD 大鼠的血管舒缩功能障碍。
