Adrenomedullin: Potential in physiology and pathophysiology

Adrenomedullin (ADM), a 52-amino acid ringed-structure peptide with C- terminal amidation, was originally isolated from human pheochromocytoma. ADM mediates vasodilatory and natriuretic properties through the second messenger cyclic adenosine 3',5'-monophosphate (cAMP), nitric oxide and the renal prostaglandin system. ADM immunoreactivity and its gene are widely distributed in cardiovascular, pulmonary, renal, gastrointestinal, cerebral and endocrine tissues. ADM is also synthesized and secreted from vascular endothelial and smooth muscle cells. When injected intravenously, ADM increases flow rates predominantly in organs in which the ADM gene is highly expressed, suggesting that ADM acts as a local autocrine and/or paracrine vasoactive hormone. In addition, ADM is a circulating hormone and its plasma concentration is increased in various cardiorenal diseases such as hypertension, chronic renal failure and congestive heart failure. Current evidence suggests that ADM plays an important role in fluid and electrolyte homeostasis and cardiorenal regulation, however further investigations are required to address the importance of ADM under various physiological and pathophysiological conditions.