氯沙坦对大鼠离体胸主动脉的舒张作用及机制

Effects of losartan on vascular tone of isolated thoracic aortic rings in rats

目的:观察氯沙坦对大鼠胸主动脉的舒张作用,并探讨其作用机制。方法:记录氯沙坦对血栓素A2(TXA2)类似物U46619、氯化钾(KCl)预收缩的离体大鼠胸主动脉环作用,观察N-硝基-L-精氨酸甲酯(L-NAME)与吲哚美辛对其作用的影响。结果:氯沙坦(3×10-8～3×10-5 mol/L)对U46619(1μmol/L)预收缩的主动脉环有内皮依赖性的、浓度依赖性的舒张作用。L-NAME(0.1mmol/L)可显著抑制氯沙坦的舒血管作用。吲哚美辛(1μmol/L)对氯沙坦的舒血管作用无明显影响。氯沙坦对KCl(60mmol/L)诱发的血管收缩无明显影响。结论:氯沙坦对U46619引起的血管收缩有浓度依赖性的舒张作用,此作用具有内皮依赖性,与内皮产生的一氧化氮(NO)有关,与前列环素(PGI2)无关。

AIM：To investigate the effects of losartan on the reactivity of the aortic rings in male wistar rats.METHODS： The effects of losartan（3×10-8-3×10-5 mol/L） on rat isolated thoracic aortic rings＇ contraction induced by TXA2 analog U46619（1 μmol/L） and KCl（60 mmol/L）were observed.In addition,the effect of the NO synthase inhibitor L-NAME（0.1 mmol/L） and the cyclooxygenase inhibitor indomethacin（1μmol/L） on losartan were observed.RESULTS：Losartan（3×10-8-3×10-5 mol/L） reduced the constriction induced by U46619（1 μmol/L） in a dose-dependent and endothelium-dependent manner.L-NAME（0.1 mmol/L）significantly shifted the concentration-response curves of losartan to the right.Indomethacin（1 μmol/L） did not change the relaxations of losartan.Losartan did not significantly affect the constriction induced by KCl（60 mmol/L）.CONCLUSION： Losartan preferentially antagonizes contraction induced by U46619 in a dose-dependent and endothelium-dependent manner.The vasorelaxation of losartan is relevant to the production of nitrogen and not relevant to the production of prostaglandin.