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肾上腺髓质素在心血管系统的分布及在心血管功能调节中的作用

魏英杰 朱燕青 曹怡雯*付爱华 张肇康**汤健

  摘 要 目的:观察肾上腺髓质素(adrenomedullin,AdM)在大鼠心血管系统的分布及缩血管活性肽对血管平滑肌细胞中肾上腺髓质素表达的影响。方法与结果:应用免疫组织化学方法(ABC法)证实,在大鼠的外周组织,尤其是主动脉和心肌等心血管组织以及培养的血管内皮细胞、血管平滑肌细胞和心肌细胞,均含有丰富的免疫活性的肾上腺髓质素。应用半定量反转录-聚合酶链式反应(RT-PCR)分析方法证实,缩血管活性肽-内皮素(ET-1)和血管紧张素Ⅱ(AGT)可明显地降低培养的血管平滑肌细胞中肾上腺髓质素mRNA水平,这一作用可选择性地分别被ET-1的特异性受体阻断剂BQ123和AGT的特异性受体阻断剂Dup753所抑制,提示ET-1/AGT可抑制肾上腺髓质素的表达。应用[3H]-TdR掺入和细胞计数发现,肾上腺髓质素可抑制培养的自发性高血压大鼠(SHR)血管平滑肌细胞的DNA合成和细胞增殖。结论:心血管系统含有丰富的肾上腺髓质素,其表达受ET-1和AGT的调控,它可能作为一种增殖抑制因子而抑制SHR血管平滑肌细胞DNA合成和细胞增殖。
  关键词 肾上腺髓质;肌,平滑,血管;免疫组织化学

Distribution of adrenomedullin in cardiovascular system and its effect on cardiovascular function

WEI Ying-Jie,ZHU Yan-Qing,CAO Yi-Wen,FU Ai-Hua,CHANG Zhao-Kang,TANG Jian
Institute of Cardiovascular Research,Beijing Medical University,Beijing(100083)

  Abstract AIM:The present study was designed to evaluate the distribution of adrenomedullin(AdM) in the cardiovascular system,and the effect of endothelin and angiotensin Ⅱ on the AdM expression in cultured vascular smooth muscle cells(VSMCs).METHODS and RESULTS:Using immunohistochemistry method(ABC method),we demonstrated that high concentration of immunoreactive AdM was widely distributed in rat peripheral tissures,especially in cardiovascular tissue including artery and heart as well as cultured vascular endothelial cells,VSMCs and cardiomyocyte.By semiquantitative reverse transcription-polymerase chain reaction(RT-PCR) analysis,we found that the levels of AdM mRNA were decreased by endothelin(ET-1) or angiotensin Ⅱ(Ang-Ⅱ) in VSMCs,which could be blocked by ET-1 antagonist BQ123 and Ang-Ⅱ antagonist Dup753,respectively.It suggested that ET-1/Ang-Ⅱ may inhibit the expression of AdM mRNA.With[3H]-TdR incorporation and cell count,we found that AdM could inhibit DNA synthesis and the proliferation of VSMCs from spontanously hypertensive rats(SHR).CONCLUSION:Plenty of AdM was widely distributed in cardiovascular system,and the exp

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