Biological and clinical roles of adrenomedullin in circulation control andcardiovascular diseases

1. Adrenomedullin(AM) is found ubiquitously in tissues and organs, especial ly in cardiovascular tissues and in the kidney, lung and endocrine glands. It has multifunctional biological properties, of which, its effects on the control of circulation and body fluid volume regulation seem to be the most outstanding and characteristic. 2. Acute administration of a high dose of AR I induces a vasodilator depres sor response, cardiac inotropic effects, diuresis and suppression of aldost erone secretion in experimental animals. 3. Long-term continuous administration of a very low dose of AM causes vaso dilation in sheep (0.5 mu g/kg per h) and hypotension in rats (0.8 mu g/kg per h), 4. The plasma concentration of AM increases under pathological conditions s uch as congestive heart failure, myocardial infarction and hypertensive and renal diseases. Under these disease conditions, AM may be produced in vasc ular endothelial and smooth muscle cells and in cardiac myocytes in respons e to volume expansion, hypertension and activated humoral factors, such as catecholanline and the renin-angiotensin system. 5. Increased API I in the circulating blood and cardiovascular tissues mag counteract pathological deviation in the system that controls circulation a nd body fluid volume, acting against cardiovascular damage and disease. 6. Because of these beneficial properties in the cardiovascular system, AM and its pharmaceutical ligands should prove useful in the treatment of card iovascular diseases.