Modulation of Nitrogen Oxide Synthesis In Vivo: N G ‐Monomethyl‐L‐Arginine Inhibits Endotoxin‐Induced Nitrate/Nitrate Biosynthesis While Promoting Hepatic Damage

Attempts were made to promote or inhibit nitric oxide (·N=O) synthesis in a murine model of hepatic damage (Corynebacterium parvum followed by lipopolysaccharide; LPS) to determine the role of N=O in the liver injury. Moderate hepatic damage and increases in circulating NO 2 ‐ /NO 3 ‐ levels were detectable after C . parvum alone. Administration of LPS to these mice resulted in severe hepatic damage and acute elevations in circulating nitrogen oxide levels. L‐arg had no influence on the C . parvum or LPS‐induced changes. N G ‐monomethyl‐L‐arginine (NMA) had no effect in the absence of LPS, but when given with LPS, a dose‐dependent suppression in plasma NO 2 ‐ /NO 3 ‐ levels and an increase in liver injury were seen. The NMA‐induced changes were partially reversed by the simultaneous administration of L‐arg. These findings suggest a protective role for · N=O in this model.