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Apelin对大鼠离体肺动脉环的舒张作用及与一氧化氮的关系

Effect of apelin on vasodilatation of isolated pulmonary arteries in rats is concerned with the nitric oxide pathway

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【作者】 黄萍范小芳庞玲霞高钰琪毛孙忠胡良冈洪林陈然龚永生

【Author】 HUANG Ping1,3,FAN Xiao-fang1,2,Pan Ling-xia1,2,GAO Yu-qi3,MAO Sun-zhong1,HU Liang-gang1,2,HONG Lin1,2,Chen Ran1,2,GONG Yong-sheng1,2,4(1.Laboratory of Cor Pulmonale,Institute of Hypoxia Medicine;2.Teaching Center of Functional Experiment;3.Department of Science and Technology,Wenzhou Medical College,Wenzhou 325035;4.Key Laboratory of High Altitude Medicine,Third Military Medical University,Chongqing 400038,China)

【机构】 温州医学院低氧医学研究所肺心病研究室温州医学院低氧医学研究所科技处温州医学院低氧医学研究所机能实验教学中心第三军医大学高原医学教育部重点实验室

【摘要】 目的:探讨新的小分子活性肽Apelin对大鼠离体肺动脉环的舒张作用及与一氧化氮(NO)途径的关系,并比较低氧大鼠的肺动脉环对Apelin的舒张反应与正常大鼠的差异。方法:36只大鼠随机分为正常组与低氧组;采用离体血管环灌流法,检测Apelin对去甲肾上腺素(NE)预收缩的大鼠离体肺主动脉环的舒张效应,观察去内皮或用一氧化氮合酶抑制剂(L-NAME)、可溶性鸟苷酸环化酶(sGC)抑制剂(ODQ)孵育后该舒张率的变化。结果:①在正常组大鼠肺动脉环,Apelin(0.01~100 nmol/L)具有浓度依赖性的舒张效应。去除内皮后,Apelin对NE预先收缩的肺血管舒张效应明显减弱(P<0.01)。L-NAME或ODQ预孵育后,Apelin的舒张效应均明显减弱(P均<0.01)。②低氧组大鼠的肺动脉环对Apelin的舒张反应明显低于正常组大鼠,在最大浓度100 nmol/L时,Apelin的效应低60.45%(P<0.01),而两组EC50相比差异无显著性(P>0.05)。结论:Apelin具有内皮依赖性的舒张肺动脉环的作用,该效应与NO-sGC-cGMP信号途径有关;低氧大鼠的离体肺动脉环对Apelin的舒张反应减弱。

【Abstract】 Objective: To investigate the effect of apelin on vasodilatation of isolated pulmonary arterial rings in rats and its relationship to the nitric oxide(NO) pathway,and to observe the difference of vasodilatation between hypoxic rats and normoxic rats.Methods: Thirty-six male Sprague-Dawley(SD)rats were randomly divided into hypoxic group and normoxic group.The effects of accumulated apelin on pulmonary arterial rings preconstricted with norepinephrine(NE) were observed by using tissue organ bath system.After pulmonary arterial rings were pretreated with three methods: removing the endothelium,pretreating with nitric oxide synthase inhibitor L-NAME or soluble guanylatecyclase inhibitor ODQ, the different effect of apelin was observed.In addition,the difference of vasodilatation between hypoxic rats and normal rats were observed.Results: ①Exposure of intact endothelium pulmonary arterial rings preconstricted by NE to apelin at concentration(0.01~100 nmol/L) induced a significant concentration dependent relaxation.The maximal vasorelaxant effect of apelin was 10.62%±2.60%,which was inhibited by removal of the endothelium(P<0.01),pretreatment with LNAME(P<0.01) or ODQ(P<0.01).②Response of pulmonary arterial rings from hypoxic pulmonary hypertension rats was decreased(P<0.05).Compared to normal rats,at a concentration of 100 nmol/L,the response to apelin on arteries from hypoxic rats decreased 60.45%(P<0.01).But the values of EC50 were not significantly different(P>0.05).Conclusion: These results indicate that apelin relaxes the pulmonary arterial rings of rats in an endothelium dependent manner,which may have a relationship to NO signaling pathway.The response of vasodilatation is decreased in the pulmonary arterial rings from the hypoxic rats.

【基金】 国家重点基础研究发展计划项目(2006CB504107);浙江省自然科学基金(Y206464,Y2091033);浙江省科技厅新苗人才计划项目(2008R40G2090029);第三军医大学高原医学教育部重点实验室资助项目(2009GK04);浙江省教育厅资助项目(20061806)
  • 【文献出处】 中国应用生理学杂志 ,Chinese Journal of Applied Physiology , 编辑部邮箱 ,2011年01期
  • 【分类号】R331.3
  • 【被引频次】14
  • 【下载频次】336
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