Angiotensin II stimulates cardiac adrenomedullin production and causes accumulation of mature adrenomedullin independently of hemodynamic stress in vivo
Angiotensin II stimulates cardiac adrenomedullin production and causes accumulation of mature adrenomedullin independently of hemodynamic stress in vivo
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DOI：
10.1055/s-2005-861471
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发表时间：
2005-05-01
影响因子：
2.2
通讯作者：
Eto, T
中科院分区：
文献类型：
--
作者：
Onitsuka, H;Imamura, T;Eto, T
肾上腺髓质素是一种有效的扩张肽，可作用于肌细胞以抑制肥大，并作用于成纤维细胞以抑制由机械拉伸和血管紧张素II诱导的体外生长。肾上腺髓质素是从无活性的中间体肾上腺髓质素前体加工而来，具有甘氨酸延伸，随后通过酶促酰胺化转化为具有生物活性的成熟肾上腺髓质素。总肾上腺髓质素是中间肾上腺髓质素和成熟肾上腺髓质素的总和。我们在体内检查了降压剂量的血管紧张素II对左心室肾上腺髓质素产生和左心室成熟肾上腺髓质素蛋白水平的影响。我们还研究了这种作用是否由血管紧张素II 1型受体介导。无论压力超负荷如何，血管紧张素II输注均显著增加左心室总肾上腺髓质素和成熟肾上腺髓质素浓度以及成熟肾上腺髓质素与中间肾上腺髓质素的比值。总肾上腺髓质素和成熟肾上腺髓质素浓度与左心室重量显著相关。此外，增加肾上腺髓质素基因表达和蛋白水平完全抑制降压剂量的血管紧张素II 1型受体阻滞剂。总之，血管紧张素II刺激心脏肾上腺髓质素的生产和积累成熟的肾上腺髓质素在左心室独立的血流动力学应激。这些过程在体内通过血管紧张素II 1型受体部分调节。
Adrenomedullin is a potent hypotensive peptide that may act on myocytes to inhibit hypertrophy and on fibroblasts to inhibit growth in vitro induced by mechanical stretching and angiotensin II. Adrenomedullin is processed from the inactive intermediate adrenomedullin precursor with a glycine extension, which is subsequently converted to biologically active mature adrenomedullin by enzymatic amidation. Total adrenomedullin is the sum of intermediate and mature adrenomedullin. We examined the effect of a subpressor dose of angiotensin II on the production of left ventricular adrenomedullin and on protein levels of mature adrenomedullin in the left ventricle in vivo. We also investigated whether the effect is mediated by the angiotensin II type 1 receptor. Concentrations of total and mature adrenomedullin in the left ventricle and mature adrenomedullin-to-intermediate adrenomedullin ratio were significantly increased by angiotensin II infusion, regardless of pressure overload. Total and mature adrenomedullin concentrations significantly correlated with the weight of the left ventricle. Furthermore, increased adrenomedullin gene expression and protein levels were completely suppressed by a subdepressor dose of angiotensin II type 1 receptor blocker. In conclusion, angiotensin II stimulates the production of cardiac adrenomedullin and accumulates mature adrenomedullin in the left ventricle independently of hemodynamic stress. These processes are partially regulated through the angiotensin II type 1 receptor in vivo.