Inhibition of Nitric Oxide Synthase During Sepsis and Endotoxemia May Be Detrimental

Abstract

Both in patients and in experimental animals sepsis and endotoxemia are associated with increased production of nitric oxide (NO), documented by urinary excretion of N03 and elevated plasma levels of nitrite and nitrate (N02/ N03), the stable end-products of NO [1–3]. Results in previous reports suggest that NO may be responsible for hemodynamic and metabolic consequences of sepsis and endotoxemia, and that inhibition of NO synthesis may be beneficial during these conditions [4–6]. Results observed in two patients with septic shock following treatment with the NO synthase inhibitor NG-monomethyl-l-arginine (NMA) were interpreted as indicating that NO contributes to the pathogenesis of septic shock, and that inhibition of NO synthesis may be a therapeutic option in septic patients [7]. In contrast, several recent studies, including reports from our laboratory, suggest that inhibition of NO synthase activity during sepsis and endotoxemia may be detrimental. Thus, evidence of increased mortality, liver and lung injury, and decreased intestinal integrity has been reported following treatment with NO synthase inhibitors during sepsis and endotoxemia.