Live and let die: asymmetric dimethylarginine and septic shock.

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.