藻酸双酯钠对大鼠离体胸主动脉的血管收缩作用

Contractile effect of alginic sodium diester on rat thoracic aorta in vitro

目的探讨藻酸双酯钠(ASD)引起心绞痛等副作用是否由其对血管的直接效应所致,并探讨其可能机制。方法采用大鼠离体血管环标本浴管内实验,观察累积浓度ASD(0.05～500mg.L-1)对血管环的作用。结果在内皮完整血管环,ASD对基础状态或KCl预收缩血管环的张力无明显影响;对去氧肾上腺素(PE)预收缩的血管环,ASD在低浓度时无明显作用,高浓度时具有收缩作用。而在PE预收缩的去内皮血管环上,ASD0.05～500mg.L-1对血管环的张力均无明显影响。内皮素转换酶抑制剂磷阿米酮和环氧化酶抑制剂吲哚美辛预孵育对PE预收缩血管环的ASD收缩作用无明显影响,血管紧张素转换酶抑制剂卡托普利预孵育可部分抑制ASD的血管收缩。ASD(500mg.L-1)对PE预收缩血管环的乙酰胆碱血管舒张效应无明显影响。结论高浓度ASD对胸主动脉具有内皮依赖性收缩作用,其机制可能部分与促进血管紧张素Ⅱ的合成和(或)激活有关。

AIM To examine whether the side effects, such as angina pectoris, of alginic sodium diester （ASD） are resulted from its direct action on blood vessels, and to investigate the underlying mechanisms. METHODS The isolated rat thoracic aortic rings were incubated with accumulated ASD （ 0.05 - 500 mg·L^-1 ） in organ bath and contraction of aortic rings was examined. RESULTS ASD had no significant effects on aortic rings with intact endothelium in resting tension or pre-constricted with KCl. In phenylephrine （ PE ） pre-constricted aortic rings with intact endothelium, accumulated ASD had no significant effects in lower concentrations（0.05 - 15 mg·L^-1 ） , but enhance the contraction markedly in higher concentrations （50 - 5000 mg·L^-1 ）. While ASD （0.05 - 500 mg·L^-1） had no significant effect on the endothelium-denuded aortic rings pre-constricted by PE. When endothelium-intact aortic rings were pre-constricted with PE, ASD-induced vasoconstriction was not affected when pre-incubated endothelium-intact aortic rings with endothelin converting enzyme inhibitor phosphoramidone or cyclooxygenase inhibitor indometacin, but was partially inhibited by preincubated with angiotensin converting enzyme inhibitor captopril. ASD （500 mg·L^-1 ） had no effect on the relaxation induced by acetylcholine in the aortic rings pre-constricted by PE. CONCLUSION High concentration of ASD has endothelium-dependent contractile effect on rat thoracic aortas, which may be mediated partially by promoting the synthesis or release of angiotensin Ⅱ.