核苷酸对ATP-敏感性钾通道开放剂吡那地尔舒血管效应的调节作用

REGULATORY EFFECTS OF NUCLEOTIDES ON ATP-SENSITIVE POTASSIUM CHANNEL OPENER PINACIDIL-INDUCED VASCULAR RELAXATION

目的 :在正常Wistar大鼠离体主动脉上 ,研究核苷酸类物质ATP ,ADP ,UDP ,GTP及其代谢产物腺苷 (Ade)对ATP敏感性钾通道 (ATP sensitivepotassiumchannel,KATP)开放剂吡那地尔 (pinacidil,Pin)舒血管效应的影响 ,以评价其对动脉平滑肌KATP功能的调节作用。方法 :大鼠离体主动脉去内皮血管环以核苷酸或核苷酸与格列本脲(Gli)孵育 10min后 ,再以KCl2 0mmol·L-1诱发收缩 ,观察Pin的血管舒张效应的变化。结果 :离体去内皮大鼠主动脉标本经ATP ,ADP ,UDP和GTP 4种核苷酸和Ade在 10 0 μmol·L-1浓度下预孵育后 ,Pin舒血管作用发生变化 :①ATP可减弱Pin对KATP的开放作用 ,但增强Gli对KATP的阻断作用。②ADP既减弱Pin对KATP的开放作用 ,又减弱Gli对KATP的阻断作用。③Ade对KATP功能的调节与ADP相似 ,既减弱Pin对KATP的开放作用 ,又减弱Gli对KATP的阻断作用。④UDP 10 0 μmol·L-1可增强Pin对KATP的开放作用 ,但减弱Gli对KATP的阻断作用。⑤GTP可增强Pin激活KATP开放的作用 ,但对Gli阻断KATP开放的作用无影响。结论 :不同的核苷酸和腺苷均可调节血管平滑肌KATP的功能 ,但其调节作用的药理学特征并不相同。

Aim: In order to evaluate the regulatory effects of nucleotides and adenosine on ATP-sensitive potassium channel (K ATP ) in artery smooth muscles, the effects of them on vascular relaxation induced by K ATP opener pinacidil(Pin) were investigated. Methods: The isolated endothelium- denuded aorta rings were preincubated with nucleotides or nucleotides and glibenclamide(Gli) for 10 min, the vascular relaxation induced by Pin in aorta precontracted with 20 mmol·L -1 KCl was observed. Results: After the isolated endothelium-denuded aorta rings were preincubated with ATP, ADP, UDP, GTP and adenosine (Ade) 100 μmol·L -1 respectively, the vascular relaxation induced by Pin was changed as following: ①ATP could inhibit the K ATP activation by Pin and enhance the blockade of K ATP by Gli. ②ADP could inhibit the K ATP activation by Pin and attenuate the blockade of K ATP by Gli. ③The regulatory effect of Ade on K ATP was similar with that of ADP. ④UDP could enhance the K ATP activation by Pin and attenuate the blockade of K ATP by Gli. ⑤GTP could enhance the K ATP activation by Pin, but had no effects on the blockade of K ATP by Gli. Conclusion: Nucleotides and adenosine, related to energy metabolism, could modulate the functions of K ATP in vascular smooth muscle. But their pharmacological characteristics were different.