重症高血压大鼠左心室肥厚时肾上腺髓质素系统的上调  

Upregulation of adrenomedullin system in left ventricular hypertrophy of severe hypertension rats

作　　者：王新[1] 锦见俊雄 李志忠[1] 李庆祥[1] 朱小玲[1] 白树功[1] 

机构地区：[1]首都医科大学附属北京安贞医院抢救中心,100029 [2]日本独协医科大学循环内科

出　　处：《中华心血管病杂志》2005年第1期77-80,共4页Chinese Journal of Cardiology

摘　　要：目的　探讨肾上腺髓质素 (AM )在重症高血压大鼠左心室心肌肥大中的病理生理作用 ,包括其配体及酰胺化活性。方法　试验分为 4组 :Wistar Kyoto大鼠为对照组 ,有卒中倾向的自然发症高血压大鼠组 ,用卡托普利治疗 8周组 ,用三氯甲噻嗪治疗 8周组。AM前体为无活性的甘氨酸基肾上腺髓质素 (AM Gly) ,AM Gly经酰胺化转变为成熟的有活性的AM (AM m)。通过放射性免疫分析 ,检测血浆和左心室中AM m、总AM (AM m +AM Gly)、心房利钠肽含量 ,以及AM和心房利钠肽基因水平。结果　自然发症高血压大鼠组血压、左心室重量、血浆和左心室中心房利钠肽及其mRNA水平均较对照有所升高。血浆中 (AM m :+31% ,总AM :+5 6 % )及心室中 (AM m :+84 % ,总AM :+31% )的AM m和总AM均较对照组显著升高。在左心室组织中自然发症高血压大鼠组 (93 2 % )的AM m/总AM比率明显高于对照组。在左心室中的AM的mRNA水平显著高于对照组。卡托普利和三氯甲噻嗪降血压和降低肥大左心室中AM m、总AM、AM的mRNA含量作用相似。结论　此高血压模型的肥大心肌中肾上腺髓质素系统上调。作为一个抗重塑的自分泌和(或 )旁分泌因子 ,AM的上调可能改变左心室肥厚的病理生理过程。Objective To investigate the pathophysiological role of the cardiac adrenomedullin (AM) system, including the ligand and amidating activity in the hypertrophied heart in severe hypertension. Methods The following four groups were studied: control Wistar Kyoto rats (WKY), spontaneously hypertensive stroke-prone rats (SHR-SP), 8 weeks captopril-treated SHR-SP, and 8 weeks trichlormethiazide-treated SHR-SP. AM precursor was converted to inactive glycine-extended AM (AM-Gly) and subsequently AM-Gly was converted to active mature AM (AM-m) by enzymatic amidation. AM-m, AM-total (AM-T; AM-T=AM-m+AM-Gly), atrial natriuretic peptide (ANP) in the plasma and left ventricle (LV) by immunoradiometric assay, and gene expression of AM and ANP were measured. Results SHR-SP had increased blood pressure, LV weight, plasma and LV ANP levels and mRNA levels of ANP compared with WKY. AM-m and AM-T levels in the plasma (AM-m:+31%; AM-T:+56%) and in the LV (AM-m:+84%; AM-T:+31%) were significantly higher in SHR-SP than those in WKY. The LV tissue AM-m/AM-T ratio was significantly higher in SHR-SP (93.2%) than that in WKY. The mRNA levels of AM in the LV were significantly higher in SHR-SP than those in WKY. Captopril and trichlormethiazide similarly decreased blood pressure and LV hypertrophy with the reduction of the LV AM-m and AM-T levels and mRNA abundance of AM. Conclusions These results suggested that cardiac AM system was upregulated in the hypertrophied heart in this hypertension model. Considering that AM being as an antiremodeling autocrine and (or) paracrine factor, upregulation of the AM system may modulate the pathophysiological course in LV hypertrophy.

关 键 词：左心室 大鼠 肾上腺髓质素 对照组 重症高血压 心房利钠肽 治疗 MRNA水平 前体 旁分泌 

分 类 号：R541.3[医药卫生—心血管疾病]