盐酸埃他卡林对动脉平滑肌钾电流的影响

Effects of iptakalim hydrochloride on potassium currents in artery smooth muscles

目的 探讨抗高血压新药盐酸埃他卡林对动脉平滑肌细胞钾电流的作用。方法 分离大鼠动脉平滑肌细胞 ,用膜片钳全细胞记录技术记录细胞钾电流 ,通过浴槽内给药 ,观察盐酸埃他卡林对钾电流的影响。结果 盐酸埃他卡林(0 1、1、10、10 0 μmol·L-1)均可明显引起正常血压大鼠肺动脉平滑肌外向钾电流I U曲线上移 ,盐酸埃他卡林作用后 5min内细胞外向钾电流强度分别增强为初始电流强度的[(118 6± 15 9) % ,P <0 0 1vscontrol,n =6 ]、[(10 3 9±5 9) % ,P <0 0 1vscontrol,n =5 ]、[(132 7± 2 3 9) % ,P <0 0 1vscontrol,n =6 ]、[(15 0 1± 2 5 1) % ,P <0 0 1vscontrol,n =7];盐酸埃他卡林 (1、10、10 0 μmol·L-1)均可引起肾性高血压大鼠肺动脉平滑肌外向钾电流I U曲线上移 ,盐酸埃他卡林作用后 5min内细胞外向钾电流强度分别增强为初始电流强度的 [(12 1 5± 4 2 ) % ,P <0 0 1vscon trol,n =7]、[(132 2± 6 7) % ,P <0 0 1vscontrol,n =8]、[(114 2± 7 7) % ,P <0 0 1vscontrol,n =8];盐酸埃他卡林 (10 μmol·L-1)可引起肺动脉高压大鼠肺动脉平滑肌外向钾电流I U曲线上移 ,盐酸埃他卡林作用后 5min内细胞外向钾电流强度为初始电流强度的 [(80 6± 10 1) % ,n =5 ]。

AIM To investigate the effects of the novel antihypertensive drug iptakalim hydrochloride on potassium currents in artery smooth muscle cells. METHODS The effects of iptakalim hydrochloride on potassium currents in smooth muscle cells derived from rat pulmonary arteries were observed by using patch clamp technique(whole cell recording) after application of the drug in the bath. RESULTS The potassium current-voltage curves ( I-U curves) of smooth muscle cells derived from normotensive rat pulmonary arteries were up-ward shifted by iptakalim hydrochloride(0.1,1,10 and 100 μmol·L -1 ). Within 5 minutes after application of the drug, the current amplitude could increase to[(118.6±15.9)%, P< 0.01 vs control, n =6],[(103.9±5.9)%, P< 0.01 vs control, n =5],[(132.7±23.9)%, P< 0.01 vs control, n =6],[(150.1±25.1)%, P< 0.01 vs control, n =7) of initial current amplitude respectively. The potassium I-U curves of smooth muscle cells derived from renal hypertensive rat pulmonary arteries were up-ward shifted by iptakalim hydrochloride (1,10 and 100 μmol·L -1 ). Within 5 minutes after application of the drug, the current amplitude could increase to[(121.5±4.2)%, P< 0.01 vs control, n =7],[(132.2±6.7)%, P< 0.01 vs control, n =8]?[(114.2±7.7)%, P< 0.01 vs control, n= 8)of initial current amplitude respectively.The potassium I-U curves of smooth muscle cells derived from pulmonary hypertensive rat pulmonary arteries were up-ward shifted after application of iptakalim hydrochloride (10 μmol·L -1 ) in extracellular solution. Within 5 minutes after application of the drug, the current amplitude changed to[(80.6±10.1)%, n= 5] of initial current amplitude while the current amplitude of control decreased to [(71.4±7.6)%, n =5] of initial current amplitude. The effects of iptakalim hydrochloride(10 μmol·L -1 ) were blocked by glybenclimade (30 μmol·L -1 ). CONCLUSIONS The out-ward potassium currents in smooth muscle cells derived from normotensive, pulmonary hypertensive and renal hypertensive rats could be increased by iptakalim hydrochloride, which could be blocked by glybenclimade, a specific ATP-sensitive potassium channels(K_ ATP ) blocker. It is reasonable to suggest that the K_ ATP channels of artery smooth muscle cells can be activated by iptakalim hydrochloride.