雷米普利酸对内外源性自由基所致离体血管内皮依赖性舒张功能影响

目的:探讨雷米普利酸(Ramiprilat)对内外源性自由基所致家兔离体胸主动脉内皮依赖性舒张功能损伤的保护作用及其作用机制。方法:采用DPPH(0.25μmol/L)或通过次黄嘌呤(HX 0.06μmol/L)和黄嘌呤氧化酶(XO 2U/L)孵育家兔离体血管环10 min,诱导血管内皮依赖性舒张功能损伤。结果:DPPH和HX+XO诱导产生氧自由基超氧阴离子(O-.2),能明显抑制胸主动脉环对乙酰胆碱(Ach)诱导的血管内皮依赖性舒张反应。用雷米普利酸(5μmol/L)预孵育血管环20 min,可明显改善DPPH和HX+XO所致血管内皮依赖性舒张反应的抑制。而预先用选择性缓激肽B2受体阻断剂HOE140(10μmol/L)孵育血管10 min,可明显抑制雷米普利酸对DPPH和HX+XO所致血管内皮依赖性舒张反应的损伤保护作用。结论:雷米普利酸对DPPH和HX+XO所致血管内皮依赖性舒张反应的损伤具有保护作用,其机制至少部分是通过激活缓激肽B2受体所介导的。

Protective Effects of Ramiprilat on Free Radical-induced the Impairment of Endothelium-dependent Relaxation in Isolated Rabbits Thoracic Aorta

Objective To examine the protective effects of Ramiprilat on the impairment of endothelium-dependent relaxation induced by free radical in isolated rabbit thoracic aorta and its possible mechanisms.Methods Aortic rings were exposed to DPPH(0.25 μmol/L)or hypoxanthine(HX,0.06 μmol/L) + oxanthineoxidse(XO,2U/L) for 10 min to induce the impairment of endothelium-dependent vasodilation.In the Ramiprilat-treated groups,aortic rings were incubated with Ramiprilat(5 μmol/L) for 10 min and then exposed to DPPH or HX(0.06 μmol/L)+XO(2U/L) for 10 min in the presence of the Ramiprilat.Vasodilator responses to acetylcholine were measured.Results DPPH or HX+XO significantly inhibited the endothelium-dependent vasodilatator responses to acetylcholine.Pre-incubation of aortic rings with Ramiprilat for 10 min and co-incubation of aortic rings with DPPH or HX+XO for another 10 min markedly attenuated inhibition of endothelium-dependent relaxation induced by DPPH or HX+XO,effect was attenuated by pre-incubation of aortic rings with BK B2-receptor antagonist(HOE140) for 10 min.Conclusion Ramiprilat can protect rabbit aortic endothelium against damage due to DPPH or HX+XO,and the beneficial effect of Ramiprilat is related to activation of bradykin B2 receptor.