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

Abstract

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 NO₂ ^-/NO₃ ^- 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 NO₂ ^-/NO₃ ^- 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.