Adrenomedullin: a Possible Autocrine or Paracrine Hormone in the Cardiac Ventricles

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Abstract
Adrenomedullin (AM), a potent vasodilator peptide originally isolated from pheochromocytoma, is expressed in cardiovascular tissues such as those of the cardiac atria and ventricles. Cell culture experiments have shown that AM peptide is synthesized and secreted from cardiac myocytes and fibroblasts of neonatal rats. Humoral factors, such as angiotensin II (Ang II) and endothelin-1 (ET-1), and mechanical stress due to pressure and volume overload to the heart have been shown to be involved in AM expression of the myocardium in both in vitro and in vivo studies. The effects of AM on cardiomyocytes and cardiac fibroblasts have been examined in in vitro studies, with the result that AM was shown to exert inhibitory actions on myocyte hypertrophy and on proliferation and collagen production of cardiac fibroblasts in an autocrine or paracrine manner. In rats, experimental therapeutic intervention consisting of transfer of the AM gene or of recombinant AM appears to partly inhibit the progression of cardiac hypertrophy and remodeling. It has been shown that the calcitonin receptor-like receptor (CRLR) and receptor-activity-modifying protein (RAMP) act together to function as AM receptors, although in this regard there are a number of issues, including the cellular mechanism of AM actions, that remain to be addressed. In addition, the role of proadrenomedullin N-terminal 20 peptide (PAMP), which is derived from preproAM, is another topic for future experiments. Collectively, the research data accumulating in this area suggest that AM plays a role as an autocrine or paracrine hormone in the cardiac ventricles, and that AM might be utilized as a therapeutic tool in the treatment of hypertensive or ischemic heart disease. (Hypertens Res 2003; 26 (Suppl): S113-S119)