NITRIC-OXIDE IN SEPSIS-SYNDROME - POTENTIAL TREATMENT OF SEPTIC SHOCKBY NITRIC-OXIDE SYNTHASE ANTAGONISTS

Nitric oxide (NO) is an effector molecule with multiple effects on var ious organ systems. The most prominent physiological actions of NO as a biological mediator include cGMP-dependent vasodilation and cytotoxi city against pathogens in the unspecific immune defense. Sepsis syndro me is a complex disease entity mostly caused by overwhelming bacterial infections. It has a high mortality rate of 40 to 60%. Catecholamine- resistant hypotension and myocardial depression are regarded as major factors contributing to death in septic patients. In septic shock, a p athophysiologically increased NO production occurs due to an excessive induction of the inducible NO synthase (iNOS). Inducible nitric oxide synthase up-regulation is probably caused by bacterial endo-and exoto xins as well as by an increase of circulating pro-inflammatory cytokin es. It may be a key factor leading to pronounced vasodilation and myoc ardial toxicity. Experimental studies have confirmed that NO overprodu ction causes severe hypotension in septic animals. Treatment with comp etitive NOS-inhibitors abolishes this hypotension in animals as well a s in septic patients. However, their use is complicated by concomitant decreases in cardiac index and oxygen delivery. Conclusive data on mo rtality in animals and patients with sepsis-syndrome treated by NOS an tagonists are not available. This article discusses current concepts c oncerning the L-aginine/NO system in the pathophysiology of and as a p otential therapeutic target in septic shock.