卡托普利抗同型半胱氨酸和溶血性磷脂酰胆碱损伤大鼠血管内皮功能

Protection of captopril against homocysteine and lysophosphatidyl-choline induced endothelium damage in isolated rat aorta

目的 研究卡托普利能否保护同型半胱氨酸(Hcy)和溶血性磷脂酰胆碱 (LPC)在体外直接损伤的大鼠离体胸主动脉内皮功能。方法 用Hcy或LPC孵育大鼠离体胸主动脉环 3 0min诱导血管内皮损伤 ,观察卡托普利对Hcy和LPC损伤血管内皮依赖性舒张反应的影响。结果 Hcy( 0 .3～ 3mmol·L-1)或LPC( 1～1 0 μmol·L-1)呈浓度依赖性地损伤乙酰胆碱诱导的内皮依赖性血管舒张反应 ,但不影响硝普钠诱导的内皮非依赖性血管舒张。卡托普利( 3～3 0 μmol·L-1)预孵育血管环 1 5min,再与Hcy( 1mmol·L-1)共同孵育 3 0min,浓度依赖性改善Hcy对血管内皮依赖性舒张反应的损害。 3 0 μmol·L-1卡托普利也可完全逆转LPC( 3 μmol·L-1)对内皮依赖性血管舒张反应的损害。

AIM To investigate if captopril can protect against the endothelium damage directly induced by homocysteine (Hcy) and lysophosphatidylcholine (LPC) in vitro. METHODS Aortic rings were incubated with various concentrations of Hcy or LPC for 30 min to induce endothelial damage. In the captopril groups, aortic rings were pre incubated with captopril for 15 min and then exposed to Hcy or LPC for another 30 min in the presence of captopril. After these incubations, the endothelium dependent relaxation response to acetylcholine and the endothelium independent relaxation response to sodium nitroprusside were examined at the plateau phase of phenylephrine contraction, respectively. RESULTS Exposure to Hcy (0.3-3 mmol·L -1 ) or LPC (1-10 μmol·L -1 ) induced a significant concentration dependent inhibition of endothelium dependent relaxation response of aortic rings to acetylcholine, but did not affect endothelium independent relaxation response to sodium nitroprusside. Pre incubation of aortic rings with captopril (3-30 μmol·L -1 ) for 15 min and co incubation of aortic rings with Hcy (1 mmol·L -1 ) for another 30 min attenuated the inhibition induced by Hcy in a concentration dependent manner. Moreover, captopril (30 μmol·L -1 ) also reversed the impairment of vasorelaxation induced by LPC (3 μmol·L -1 ). CONCLUSION Captopril has protective effects against damages of vascular endothelium induced by Hcy and LPC.