Adrenomedullin and heart failure.
Evidence suggests that adrenomedullin (AM) plays a role in the pathophysiology of heart failure. Circulating concentrations of AM are elevated in cardiovascular disease in proportion to the severity of cardiac and hemodynamic impairment. Raised plasma AM levels following acute cardiac injury and in heart failure provide prognostic information on adverse outcomes. In heart failure, elevated circulating AM also identifies patients likely to receive long-term benefit from inclusion of additional anti-failure therapy (carvedilol). Administration of AM in experimental and human heart failure induces reductions in arterial pressure and cardiac filling pressures, and improves cardiac output, in association with inhibition of plasma aldosterone (despite increased renin release) and sustained (or augmented) renal glomerular filtration and sodium excretion. Furthermore, AM in combination with other therapies (angiotensin-converting enzyme inhibition and augmentation of the natriuretic peptides) results in hemodynamic and renal benefits greater than those achieved by the agents separately. Manipulation of the AM system holds promise as a therapeutic strategy in cardiac disease.
Rademaker
Miriam T
MT
The Christchurch Cardioendocrine Research Group, Department of Medicine, The Christchurch School of Medicine, PO Box 4345, Christchurch, New Zealand. miriam.rademaker@chmeds.ac.nz
Cameron
Vicky A
VA
Charles
Christopher J
CJ
Lainchbury
John G
JG
Nicholls
M Gary
MG
Richards
A Mark
AM
D053607:Adrenomedullin; D000595:Amino Acid Sequence; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D006333:Heart Failure / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008969:Molecular Sequence Data; D020097:Natriuretic Peptide, Brain / Q000627:therapeutic use; D010455:Peptides / Q000097:blood* / Q000737:chemistry / Q000627:therapeutic use*; D016415:Sequence Alignment; D012756:Sheep
D000806:Angiotensin-Converting Enzyme Inhibitors; D010455:Peptides; D020097:Natriuretic Peptide, Brain; D053607:Adrenomedullin