Jougasaki M, Grantham J A, Redfield M M, Burnett J C
Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Peptides. 2001 Nov;22(11):1841-50. doi: 10.1016/s0196-9781(01)00527-7.
Adrenomedullin (ADM), a potent natriuretic and vasorelaxing peptide with inotropic properties, is elevated in plasma in human and experimental congestive heart failure (CHF). Recent studies suggest that angiotensin II stimulates ADM production and secretion from cardiac myocytes and fibroblasts. In the present study, we investigated cardiac ADM in experimental CHF, and tested the hypothesis that angiotensin converting enzyme (ACE) inhibition modulates cardiac ADM in CHF. Cardiac tissue ADM immunoreactivity and gene expression were assessed by radioimmunoassay, immunohistochemistry, in situ hybridization and Northern blot analysis in normal and CHF dogs in the presence and absence of ACE inhibition. Experimental CHF was produced by progressive rapid ventricular pacing and characterized by increased ventricular ADM concentrations as well as increased ventricular ADM gene expression. ACE inhibition abolished the increases in ventricular ADM concentrations and ventricular ADM gene expression in CHF. Ventricular ADM gene expression was localized to ventricular myocytes and correlated with left ventricular mass index, suggesting that ventricular ADM is a marker for ventricular hypertrophy. In contrast, atrial ADM concentrations and gene expression did not change in CHF with or without ACE inhibition. Increased plasma ADM concentrations in CHF were also abolished with ACE inhibition. The present study demonstrates that circulating and ventricular ADM are activated in pacing-induced experimental CHF and that ACE inhibition reverses ventricular ADM activation in CHF. This study also indicates that cardiac ADM gene expression is differently regulated between atrium and ventricle in CHF.
肾上腺髓质素（ADM）是一种具有正性肌力作用的强效利钠和血管舒张肽，在人类和实验性充血性心力衰竭（CHF）患者的血浆中水平升高。最近的研究表明，血管紧张素II可刺激心肌细胞和成纤维细胞产生和分泌ADM。在本研究中，我们调查了实验性CHF中的心脏ADM，并检验了血管紧张素转换酶（ACE）抑制可调节CHF中心脏ADM的这一假设。在有或无ACE抑制的情况下，通过放射免疫测定、免疫组织化学、原位杂交和Northern印迹分析，评估正常和CHF犬心脏组织中的ADM免疫反应性和基因表达。通过逐步快速心室起搏诱导实验性CHF，其特征为心室ADM浓度增加以及心室ADM基因表达增加。ACE抑制消除了CHF中室性ADM浓度和心室ADM基因表达的增加。心室ADM基因表达定位于心室肌细胞，并与左心室质量指数相关，提示心室ADM是心室肥大的标志物。相比之下，无论有无ACE抑制，CHF时心房ADM浓度和基因表达均无变化。ACE抑制也消除了CHF时血浆ADM浓度的升高。本研究表明，在起搏诱导的实验性CHF中，循环和心室ADM被激活，且ACE抑制可逆转CHF时心室ADM的激活。本研究还表明，CHF时心房和心室中心脏ADM基因表达的调节方式不同。
