TRPV4在高血压小鼠胸主动脉舒张中的作用

Effect of TRPV4 in the diastole of thoracic aorta in hypertensive mice

目的:研究瞬时受体电位香草素亚型4(transient receptor potential vanilloid type 4,TRPV4)在高血压小鼠胸主动脉舒张中的作用,并探讨其作用机制。方法:分离小鼠胸主动脉,取其离体胸主动脉血管环进行血管张力测试,以1μmol/L盐酸苯肾上腺素预收缩血管,分别观察对照组与TRPV4抑制剂HC067064处理组在乙酰胆碱(ACh)和GSK1016790A介导下血管张力变化,野生型与TRPV4基因敲除(TRPV4-/-)小鼠在ACh和GSK1016790A介导下血管张力变化;对于普通饮食组和高盐饮食组小鼠胸主动脉环进行血管张力测试,检测GSK1016970A舒张血管的张力变化。结果:HC067064组在ACh和GSK1016790A引起的动脉舒张反应明显低于对照组(P<0.05);TRPV4-/-小鼠胸主动脉环在ACh和GSK1016790A引起的动脉舒张反应亦低于野生型小鼠(P<0.05);高盐饮食组GSK1016790A引起的动脉舒张反应低于普通饮食组(P<0.05)。结论:TRPV4参与了小鼠胸主动脉的舒张作用,此作用是通过刺激TRPV4通道开放,促进内皮细胞外钙离子内流进入胞内,经过一系列信号转导,继而舒张血管;但是在病理模型,如高盐饮食下,TRPV4在胸主动脉中的舒张作用会被抑制。

Objective ：To investigate the role of transient receptor potential vanilloid type 4 （TRPV4） in the diastole of thoracic aorta in hypertensive ,nice, and explore its mechanism. Methods ： The vascular tension of thoracic aorta in mouse was measured. The vasocon-striction was pre-contracted with 1 μmol/L phenylephrine hydrochloride （ Phe ）. The vascular tension changes mediated by ACh and GSKI016790A in control group and TRPV4 inhibitor HC067064 treating group were observed, and the vascular tension changes media-ted by ACh and GSKI016790A in wild type and TRPV4 knockout（TRPV4 -/- ） ,nice were obsevred. The vascular tension of the tho-racic aorta rings in normal diet group and high salt diet group were measured to detect the vascular tension change induced by GSKI016970A. Results ：The arterial diastole response induced by ACh and GSKI016790A in HC067064 group was significantly lower than that in control group（P 〈0.05）. The arterial diastole response induced by ACh and GSKI016790A in thoracic aorta rings of TR- PV4 -/- ,nice was lower than that in wildtype ,nice（P 〈 0.05 ）. The arterial diastole response induced by GSKI016790A in high salt diet group was lower than that in normal diet group（ P 〈 0.05 ）. Conclusions ：TRPV4 is involved in the diastole of the thoracic aorta in ,nice. The action mechanism is to stimulate the opening of the TRPV4 channel, promote the extracellular calcium ion influx into the in-tracellular, and relax the blood vessels after a series of signal transduction. But for the pathological models, such as highsalt diet, the re-laxation of TRPV4 in thoracic aorta can be inhibited.