Accelerated cardiac hypertrophy and renal damage induced by angiotensin II in adrenomedullin knockout mice
Accelerated cardiac hypertrophy and renal damage induced by angiotensin II in adrenomedullin knockout mice
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DOI：
10.1291/hypres.26.731
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发表时间：
2003-09-01
影响因子：
5.4
通讯作者：
Nagai, R
中科院分区：
文献类型：
--
作者：
Niu, P;Shindo, T;Nagai, R
肾上腺髓质素（AM）是一种有效的血管舒张和利钠肽，被认为在心血管功能中起重要作用。AM是否参与心肌肥厚和肾损害的发生仍有争议。在本研究中，我们利用AM基因（AM+/-）的杂合子敲除小鼠，分析了内源性AM基因的生理和病理作用。与野生型（AM+/+）小鼠相比，体型或心脏和肾脏重量没有差异。然而，血管紧张素II （Ang II）输注导致AM+/-小鼠更严重的心脏肥厚。AM+/-小鼠心脏重量与体重比和左心室壁厚的增加更为明显。以肌酸酐清除率（C-cr）降低为特征的肾功能障碍在AM+/-输注Ang II后更为严重。这些结果提示AM在心肌肥厚和肾功能障碍的防御机制中起重要作用。对这些作用的更好理解可能为预防心血管疾病的新药理学方法铺平道路。
Adrenomedullin (AM) is a potent vasodilating and natriuretic peptide that is thought to play important roles in cardiovascular function. Whether or not AM is involved in the development of cardiac hypertrophy and renal damage remains controversial. In the present study, using heterozygote knockout mice of the AM gene (AM+/-), we analyzed the physiological and pathological roles of the endogenous AM gene. There were no differences in body size or heart and kidney weight compared with wild-type (AM+/+) mice. However, angiotensin II (Ang II) infusion resulted in more severe cardiac hypertrophy in AM+/- mice. The increases in the heart weight-to-body weight ratio and wall thickness of the left ventricle were more prominent in the AM+/- mice. Renal dysfunction characterized by decreased creatinine clearance (C-cr) was more severe in AM+/- after Ang II infusion. These results suggest that AM plays critical roles in the defense mechanism against cardiac hypertrophy and renal dysfunction. An improved understanding of these roles may pave the way to a novel pharmacological approach for the prevention of cardiovascular diseases.