Adrenomedullin: a cardiac depressant factor in septic shock.
Despite intensive research, septic shock is still the most common cause of death in surgical intensive care, and its incidence keeps increasing. No curative treatment is yet available. The critical aspect of septic shock is the refractory hypotension that develops during its late phase which leads to a progressive deterioration of cell and organ functions, and in most instances, death. During septic shock, following the overproduction of cytokines, many factors such as nitric oxide and adrenomedullin (ADM) are produced in abnormally large quantities, but our understanding of their contribution to the pathophysiology of sepsis is limited. Here we show that adrenomedullin (22-52), an adrenomedullin receptor antagonist, improves the contractility of myocytes isolated from lipopolysaccharide (LPS)-treated rats, whereas in normal myocytes, adrenomedullin, acting through an adrenomedullin (22-52) sensitive receptor, decreases their contractility. In addition, adrenomedullin antiserum and inducible nitric oxide (NO) synthase inhibitor improve the survival of LPS-treated rats. The data indicate that adrenomedullin is a cardiac depressant factor, which along with NO precipitates ventricular failure during septic shock.
Hyvelin
Jean-Marc
JM
Department of Physiology, Institute of Cardiovascular Sciences and Medicine, The University of Hong Kong, Hong Kong SAR, China.
Shan
Qixian
Q
Bourreau
Jean-Pierre
JP
D000262:Adenylyl Cyclases / Q000187:drug effects; D053607:Adrenomedullin; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000097:blood* / Q000494:pharmacology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D010455:Peptides / Q000097:blood* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000097:blood*; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D016276:Ventricular Function / Q000187:drug effects
D015415:Biomarkers; D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D006146:Guanidines; D008070:Lipopolysaccharides; D009566:Nitrates; D010455:Peptides; D053607:Adrenomedullin; D000262:Adenylyl Cyclases; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester