TRPV4 在渗透压对大鼠心肌收缩性影响中的作用(英文)

Role of transient receptor potential vanilloid 4 in the effect of osmotic pressure on myocardial contractility in rat

本文旨在探讨低渗和高渗内环境对心肌收缩性的影响及机制。取Sprague-Dawley(SD)大鼠左心室乳头状肌,在电刺激引起兴奋的条件下,分别记录在低渗、等渗和高渗灌流液中肌条的收缩力;同样条件下观察在低渗、等渗和高渗灌流液中加入渗透压敏感蛋白瞬时感受器电位离子通道家族香草素受体亚家族IV型(transient receptor potential vanilloid4,TRPV4)的拮抗剂和激动剂后肌条收缩力的变化。结果显示:(1)与等渗(310mOsm/L)时心肌收缩力相比,渗透压为290、270和230mOsm/L时心肌收缩力分别增加11.5%、21.5%、25.0%(P<0.05);渗透压为350、370、390mOsm/L时心肌收缩力分别降低16.0%、23.7%、55.2%(P<0.05)。(2)在低渗液(270mOsm/L)中加入TRPV4拮抗剂钌红(ruthenium red,RR),低渗对心肌收缩力的增强作用被抑制36%(P<0.01);在高渗液(390mOsm/L)中加入RR,高渗对心肌收缩力的抑制作用增加56.1%(P<0.01)。(3)在等渗液中(310mOsm/L)加入TRPV4激动剂4-α-佛波醇-12,13-二癸酸(4-α-phorbol-12,13-didecanoate,4α-PDD),心肌收缩力没有改变;在高渗液中(390mOsm/L)加入4α-PDD,高渗对心肌收缩力的抑制作用增加27.1%(P<0.01)。以上结果提示,TRPV4参与渗透压引起的心肌收缩力变化。

The aim of the present study was to investigate the influence of osmotic pressure on myocardial contractility and the possible mechanism. Electrical stimulation was used to excite papillary muscles of the left ventricle of Sprague-Dawley （SD） rats. The contractilities of myocardium in hyposmotic, isosmotic, and hyperosmotic perfusates were recorded. The influences of agonist and antagonist of the transient receptor potential vanilloid 4 （TRPV4） on the contractility of myocardium under hyposmotic, isosmotic and hyperosmotic conditions were observed. The results were as follows： （1） Compared with that under isosmotic condition （310 mOsm/L）, the myocardial contractility was increased by 11.5%, 21.5% and 25.0% （P〈0.05） under hyposmotic conditions when the osmotic pressure was at 290, 270 and 230 mOsm/L, respectively; and was decreased by 16.0%, 23.7% and 55.2% （P〈0.05） under hyperosmotic conditions when the osmotic pressure was at 350, 370 and 390 mOsm/L, respectively, （2） When ruthenium red （RR）, an antagonist of TRPV4, was added to the hyposmotic perfusate （270 mOsm/L）, the positive inotropic effect of hyposmia was restrained by 36% （P〈0.01）; and when RR was added to the hyperosmotic perfusate （390 mOsm/L）, the inhibitory effect of hyperosmia on myocardial contractility was increased by 56.1% （P〈0.01）. （3） When 4-α-phorbol-12,13-didecanoate （4α-PDD）, an agonist of TRPV4, was added to the i sosmotic perfusate （310 mOsm/L）, the myocardial contractility did not change; and when 4α-PDD was added to the hyperosmotic perfusate （390 mOsm/L）, the inhibition of myocardial contractility by hyperosmia was increased by 27.1% （P〈0.01）. These results obtained indicate that TRPV4 is possibly involved in the osmotic pressure-induced inotropic effect.