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

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

目的：观察肾上腺髓质素（ａｄｒｅｎｏｍｅｄｕｌｉｎ，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。

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 BQ 123 and Ang-Ⅱ antagonist Dup753,respectively.It suggested that ET-1/Ang-Ⅱ may inhibit the expression of AdM mRNA.With-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 expression of AdM mRNA is regulated by ET-1 and AGT.Besides,AdM may act as an inhibitor on DNA synthesis and cell proliferation of SHR VSMCs.