PROTECTIVE ROLE OF NO IN HEPATIC MICROCIRCULATORY DYSFUNCTION DURING ENDOTOXEMIA

Nitric oxide (NO) has been reported to have a protective function in a ttenuating hepatic injury during endotoxemia or sepsis. As a result, t he role of NO in attenuating the hepatic microcirculatory alterations associated with endotoxemia was investigated in mice by in vivo micros copy. The livers were examined 2 h after intravenous injection of Esch erichia coli 0111:B4 lipopolysaccharide (LPS) alone or in combination with inhibitors of the synthesis of NO, N-G-nitro-L-arginine methyl es ter or N-G-monomethyl-L-arginine. In the animals treated with the comb ination of NO synthase inhibitors and LPS, leukocyte adherence was inc reased threefold above that in animals treated with LPS alone. This wa s accompanied by a 33% reduction in sinusoidal blood flow. Simultaneou s administration of L-arginine, but not D-arginine, eliminated these m icrocirculatory disturbances. The results demonstrate that inhibition of LPS-stimulated NO production results in an early hepatic microvascu lar inflammatory response to a dose of endotoxin which by itself is sc arcely inflammatory. This suggests that NO plays a significant role in stabilizing the hepatic microcirculation during endotoxemia, thereby helping to protect the liver from ischemia and leukocyte-induced oxida tive injury.