Biological and clinical roles of adrenomedullin in circulation control and cardiovascular diseases.
1. Adrenomedullin (AM) is found ubiquitously in tissues and organs, especially 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 AM induces a vasodilator depressor response, cardiac inotropic effects, diuresis and suppression of aldosterone secretion in experimental animals. 3. Long-term continuous administration of a very low dose of AM causes vasodilation in sheep (0.5 microgram/kg per h) and hypotension in rats (0.8 microgram/kg per h). 4. The plasma concentration of AM increases under pathological conditions such as congestive heart failure, myocardial infarction and hypertensive and renal diseases. Under these disease conditions, AM may be produced in vascular endothelial and smooth muscle cells and in cardiac myocytes in response to volume expansion, hypertension and activated humoral factors, such as catecholamine and the renin-angiotensin system. 5. Increased AM in the circulating blood and cardiovascular tissues may counteract pathological deviation in the system that controls circulation and 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 cardiovascular diseases.
Eto
T
T
First Department of Internal Medicine, Miyazaki Medical College, Japan. keto@post.miyazaki-med.ac.jp
Kitamura
K
K
Kato
J
J
D053607:Adrenomedullin; D000818:Animals; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D002320:Cardiovascular Physiological Phenomena; D006801:Humans; D007674:Kidney Diseases / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000235:genetics / Q000378:metabolism / Q000493:pharmacokinetics / Q000502:physiology*; D015398:Signal Transduction; D014018:Tissue Distribution
D010455:Peptides; D053607:Adrenomedullin