THE EFFECT OF EXOGENOUS NITRIC-OXIDE ON PLASMINOGEN-ACTIVATOR INHIBITOR IN EXPERIMENTALLY-INDUCED ENDOTOXEMIA

This study evaluates the effect of exogenous nitric oxide (NO), S-nitr oso-N-acetyl-penicillamine (SNAP) on plasminogen activator inhibitor ( PAI) activity and glomerular fibrin deposition in rats with experiment ally induced endotoxemia. PAI activity increased in rats after Lipopol ysaccharide (LPS) administration and in rats receiving a nitric oxide synthase inhibitor, N-G-nitroso-L-arginine methyl ester (L-NAME). The combination of LPS and L-NAME further increase PAI activity as compare d with LPS alone (P<0.05). By contrast, the administration of SNAP to LPS rats reduced the increase in PAI activity and inhibited the additi onal increase in PAI activity induced by L-NAME. Plasma levels of plas minogen and antiplasmin were unchanged in all the studied groups. Whil e rats receiving LPS+L-NAME developed glomerular thrombosis, the addit ion of SNAP significantly reduced fibrin deposition of the glomeruli ( P<0.01). This data suggests that NO affects the fibrinolytic system du ring endotoxemia by modulating PAI activity. Thus NO, to some degree, can protect against the procoagulant effect of LPS.