THE EFFECT OF NITRIC-OXIDE SYNTHASE INHIBITION ON THE PLASMA FIBRINOLYTIC SYSTEM IN SEPTIC SHOCK IN RATS

1 We have investigated the effect of pretreatment of rats with nitric oxide (NO) synthase inhibitor, N-G-nitro-L-arginine methyl ester (L-NAME) on the E. coli lipopolysaccharide (LPS)-induced changes in the plasma frbrinolytic system, platelet count, fibrinogen level, as well as in gross and microscopic pathophysiological changes indicative of disseminated intravascular coagulation (DIC) in rats. 2 E. coli LPS (6 mg kg(-1), i.p.) produced a decrease in the levels of plasma fibrinogen and a drop in the blood platelet count 6h after administration. The decrease in fibrinogen but not the drop in platelet count was reversed by pretreatment with L-NAME (30 mg kg(-1), i.p., 24 h and 15 min before administration of LPS). 3 Pretreatment with L-NAME antagonized the LPS-induced activation of fibrinolysis as measured by changes in the euglobulin clot lysis time (ECLT) and enhanced the LPS-induced rise in the plasma level of plasminogen activator inhibitor (PAI). In animals pretreated with L-NAME there was also a marked reduction in the histological changes indicative of DIC. 4 We propose that L-NAME can act as a protective agent in LPS-induced DIC, and this protection is due to an increased generation of PAI following inhibition of NO synthase.