高盐抑制胸主动脉内皮细胞一氧化氮生成及其机制

High salt inhibits nitric oxide production in thoracic aortic endothelial cells and its mechanism

目的探究小鼠胸主动脉内皮细胞高盐模型对一氧化氮(nitric oxide,NO)生成的影响。方法使用瞬时受体电位香草素4(transient receptor potential vanilloid 4,TRPV4)抑制剂HC067047对胸主动脉内皮细胞预孵育后,通过钙离子荧光探针Fluo-4和NO荧光探针DAF-FM DA进行Ca^2+以及NO标记,研究TRPV4对NO产生的影响。以60 mmol·L^-1高盐刺激胸主动脉内皮细胞,检测Ca^2+内流以及NO的生成情况。结果与对照组相比,抑制TRPV4减少胸主动脉内皮细胞Ca 2+内流及NO的生成;与同渗透压的甘露醇相比,高盐抑制胸主动脉内皮细胞中TRPV4介导的Ca 2+内流及NO的生成。结论高盐状态下,通过抑制TRPV4通道导致Ca^2+内流减少,NO的生成下降。

Aim To investigate the effect of high-salt model of mouse thoracic aortic endothelial cells on the production of nitric oxide(NO). Methods After pre-incubation of thoracic aortic endothelial cells with transient receptor potential vanilloid 4(TRPV4) inhibitor HC067047, the effects of TRPV4 on NO production were studied by Ca ^2+ and NO staining with calcium ion fluorescent probe Fluo-4 and NO fluorescent probe DAF-FM DA. The thoracic aortic endothelial cells were stimulated with a high salt concentration of 60 mmol·L ^-1 to detect Ca ^2+ influx and NO production. Results Compared with control group, suppression of TRPV4 inhibited Ca ^2+ influx and NO production in thoracic aortic endothelial cells, and high salt conditions inhibited TRPV4-medicated Ca 2+ influx and NO production compared with mannitol under the same osmotic pressure. Conclusion In high salt state, the inhibition of TRPV4 channel leads to the decrease of Ca ^2+ influx and the down-regulation of NO synthesis.