Live and let die: asymmetric dimethylarginine and septic shock

被引:0
作者
Rainer H Böger
机构
[1] University Hospital Hamburg-Eppendorf,Clinical Pharmacology Unit, Institute of Experimental and Clinical Pharmacology
来源
Critical Care | / 10卷
关键词
Nitric Oxide; Septic Shock; Sequential Organ Failure Assessment; Sequential Organ Failure Assessment Score; ADMA Level;
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摘要
Nitric oxide (NO) is an important mediator of host defence and of vascular tone. In septic shock, upregulation of inducible NO synthase leads to the production of vast amounts of NO, which contribute to pathogen elimination but also to inappropriate vasodilation and to loss of vascular resistance. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthases shown to contribute to the regulation of vascular tone. ADMA was recently identified as a marker of organ dysfunction and mortality in intensive care patients and as a novel cardiovascular risk factor. In the present issue of Critical Care, a study by O'Dwyer and colleagues identifies ADMA as a potential regulator of NO production in septic shock. Being an inhibitor of NO production, ADMA may at least partly counteract pathological hypotension, but at the same time may impair the NO-dependent host defence. A mechanism is proposed by which the interplay between ADMA and inducible NO synthase activity is mediated. ADMA levels should be determined in future studies evaluating the regulation of NO in the intensive care setting.
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[1]  
O'Dwyer MJ(2006)Septic shock is correlated with asymmetrical dimethyl arginine levels, which may be influenced by a polymorphism in the dimethylarginine dimethylaminohydrolase II gene: a prospective observational study Crit Care 10 R139-214
[2]  
Dempsey F(1999)Treating patients with severe sepsis N Engl J Med 340 207-91
[3]  
Crowley V(1998)The discovery of nitric oxide as a key mediator in septic shock Sepsis 1 85-E24
[4]  
Kelleher D(2000)iNOS gene expression modulates microvascular responsiveness in endotoxin-challenged mice Circ Res 87 E18-295
[5]  
McManus R(1998)Effect of aminoguanidine on plasma nitric oxide by-products and blood flow during chronic peritoneal sepsis Shock 9 289-30
[6]  
Ryan T(2004)Multiple-center, randomized, placebo-controlled, double-blind study of the nitric oxide synthase inhibitor 546C88: effect on survival in patients with septic shock Crit Care Med 32 21-442
[7]  
Wheeler AP(1999)Inducible nitric oxide synthase (iNOS) gene deficiency increases the mortality of sepsis in mice Surgery 126 438-833
[8]  
Bernard GR(2003)The emerging role of asymmetric dimethylarginine as a novel cardiovascular risk factor Cardiovasc Res 59 824-1818
[9]  
Kilbourn R(2004)Asymmetrical dimethylarginine: the Uber marker? Circulation 109 1813-1030
[10]  
Boyle WA(2004)Cardiovascular biology of the asymmetric dimethylarginine: dimethylarginine dimethylaminohydrolase pathway Arterioscler Thromb Vasc Biol 24 1023-136