螺内酯对离体大鼠胸主动脉环舒张功能的作用和机制

Effect of spironolactone on vasodilatation of rat isolated thoracic aortas

目的研究螺内酯(spironolactone,SPT)对离体血管平滑肌张力影响,同时探讨SPT的作用机制。方法离体血管平滑肌张力记录法,应用SPT,观测其对Sprague Dawley(SD)大鼠离体胸主动脉环的作用及不同工具药的影响。结果 SPT对KCl(30 mmol.L-1)和NE(1μmol.L-1)预收缩的血管环具有浓度依赖的舒张作用,对内皮完整和去内皮血管环舒张作用无差异,该舒张作用为非内皮依赖性。Na+/H+交换阻滞剂氨氯吡咪(amiloride,AM,1μmol.L-1)对SPT的舒血管作用有抑制作用。在KCl预收缩基础上,加入钾通道阻断剂氯化钡(BaCl2,2μmol.L-1)、四乙胺(TEA,0.2 mol.L-1)、四氨基吡啶(4-AP,1 mmol.L-1)均不能抑制SPT的舒血管效应,ATP敏感钾通道(KATP)格列苯脲(Gli,10μmol.L-1)能抑制SPT对血管的舒张作用。在无钙的生理盐溶液中,SPT对CaCl2收缩血管有明显抑制作用。结论 SPT舒张血管的作用具有浓度依赖性,其作用机制可能与抑制Na+/H+交换、ATP敏感钾通道(KATP)以及钙离子内流有关。

Aim To investigate the effect of spironolactone（SPT） on isolated vascular smooth muscle tension and to explore the mechanism of the SPT.Methods The isolated thoracic aortic rings of male Sprague Dawley（SD） rats were mounted on the organ bath and tension was recorded.The effect of SPT on the ringswith endothelium intact or endothelium denuded precontracted by the potassium chloride（KCl,30 mmol.L-1） or norepinephrine（NE,1 μmol.L-1）,and the effect of SPT on the vessel reaction induced by various drugs were recorded with Powerlab biological signal assay system.Results SPT completely relaxed the contractions induced by KCl and NE in a concentrationdependent manner in endothelium intact and endothelium-denuded rat aorta.The vasodilator effect of SPT was partially inhibited by amiloride（1 μmol.L-1）.The vasodilator effect of SPT was not statistically inhibited by barium chloride（BaCl 2,2 μmol.L-1）,tetraethtylamine（TEA,0.2 mmol.L-1）,4-aminopyridine（4-AP,1 mmol.L-1） in KCl pre-contracted thoracic aortic rings,but inhibited by glibenclamide（Gli,10 μmol.L-1）.SPT could not inhibit the contraction induced by additions of NE in Ca 2 ＋-free PSS,but significantly inhibit the contraction induced by additions of CaCl 2.Conclusion SPT-induced vasodilatation is mainly related to inhibiting Na ＋ / H ＋ exchanger,blocking ATP-sensitive potassium channel,and interfering intracellular calcium homeostasis by blocking Ca 2 ＋ influx.