M. Ketteler et al., NITRIC-OXIDE IN SEPSIS-SYNDROME - POTENTIAL TREATMENT OF SEPTIC SHOCKBY NITRIC-OXIDE SYNTHASE ANTAGONISTS, Kidney international, 1998, pp. 27-30
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.