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, NG-nitro-L-arginine methyl ester (L-NAME) on the E. coli lipopolysaccharide (LPS)-induced changes in the plasma fibrinolytic 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 6 h 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.
Korbut
R
R
William Harvey Research Institute, Saint Bartholomew's Hospital Medical College, London.
Warner
T D
TD
Gryglewski
R J
RJ
Vane
J R
JR
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D004211:Disseminated Intravascular Coagulation / Q000097:blood; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D015849:Plasminogen Inactivators / Q000378:metabolism; D010976:Platelet Count / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000503:physiopathology*
D008070:Lipopolysaccharides; D015849:Plasminogen Inactivators; D005340:Fibrinogen; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester