Wang Yu, Liu Ling, Tao Hongmei, Wen Li, Qin Shu
Department of Cardiovascular Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Heart Vessels. 2020 Dec;35(12):1755-1765. doi: 10.1007/s00380-020-01682-1. Epub 2020 Aug 25.
Increased blood pressure variability (BPV) has been proved to be associated with cardiovascular morbidity and mortality. It is of great significance to elucidate the mechanism of BPV increase. The cation channel transient receptor potential canonical 6 (TRPC6) is involved in a series of cardiovascular disease. Our experiment aimed to explore the role of TRPC6 in the development of BPV increase. Sino-aortic denervation (SAD) operation was applied to establish the model of BPV increase in rats. The BPV was presented as the standard deviation to the mean of systolic or diastolic blood pressure every 1 h during 12 h of the light period. SAD was performed in male Sprague Dawley (SD) rats at the age of 10 weeks. At 8 weeks after SAD operation, the hemodynamic parameters were determined non-invasively via a Rodent Blood Pressure Analysis System. The TRPC6 expressions in myocardial and thoracic aortic tissue was determined utilizing Western Blot, immunofluorescence and quantitative RT-PCR. The expression of TRPC3 was detected as well. To investigate whether TRPC6 was a causative factor of BPV increase in SAD rats, TRPC6 activator and inhibitor with three progressively increasing doses were intraperitoneally injected to the SAD rats. We found that SAD rats presented significant augmentation of systolic and diastolic BPV with no change of BP level and heart rate. The mRNA and protein expression levels of TRPC6 in myocardial and thoracic aortic tissue in SAD rats were substantially increased, but there was no obvious change in TRPC3 expression. The systolic and diastolic BPV increase were dose-dependently exacerbated after TRPC6 activation with GSK1702934A but were dose-dependently attenuated after TRPC6 inhibition with SAR7334. In Conclusion, the TRPC6 (but not TRPC3) expressions in myocardial and thoracic aortic tissue were substantially increased in SAD rats, and TRPC6 probably played an important role in the development of BPV elevation.
血压变异性（BPV）增加已被证明与心血管疾病的发病率和死亡率相关。阐明BPV升高的机制具有重要意义。阳离子通道瞬时受体电位经典型6（TRPC6）参与一系列心血管疾病。我们的实验旨在探讨TRPC6在BPV升高发展中的作用。采用去窦弓神经（SAD）手术建立大鼠BPV升高模型。BPV以光照期12小时内每1小时收缩压或舒张压平均值的标准差表示。对10周龄的雄性Sprague Dawley（SD）大鼠进行SAD手术。在SAD手术后8周，通过啮齿动物血压分析系统无创测定血流动力学参数。利用蛋白质免疫印迹法、免疫荧光法和定量逆转录-聚合酶链反应法测定心肌和胸主动脉组织中TRPC6的表达。同时检测TRPC3的表达。为了研究TRPC6是否是SAD大鼠BPV升高的病因，将三种剂量逐渐增加的TRPC6激活剂和抑制剂腹腔注射到SAD大鼠体内。我们发现，SAD大鼠的收缩压和舒张压BPV显著升高，而血压水平和心率无变化。SAD大鼠心肌和胸主动脉组织中TRPC6的mRNA和蛋白表达水平显著增加，但TRPC3表达无明显变化。用GSK1702934A激活TRPC6后，收缩压和舒张压BPV升高呈剂量依赖性加剧，而用SAR7334抑制TRPC6后则呈剂量依赖性减弱。总之，SAD大鼠心肌和胸主动脉组织中TRPC6（而非TRPC3）表达显著增加，TRPC6可能在BPV升高的发展中起重要作用。
