EFFECT OF MODIFYING NITRIC-OXIDE PATHWAY ON LIVER CIRCULATION IN A RABBIT ENDOTOXIN-SHOCK MODEL

The role of nitric oxide (NO) inhibition on liver circulation during s epsis is unknown. To answer this question, we studied the effects of L -arginine (the substrate for the NO synthase), linsidomine (a direct N O donor), and N-omega-nitro-L-arginine (an NO inhibitor) on the liver circulation in anesthetized rabbits previously injected with endotoxin (Escherichia coli, Salmonella enteridis, and Salmonella minnesota, 40 0 mu g each). After endotoxin administration, and without fluid resusc itation, rabbits showed a hypodynamic shock with decrease in mean arte rial pressure (MAP) and aortic blood flow velocity. Portal vein blood flow velocity decreased, whereas hepatic artery blood flow velocity in creased. Saline or treatments were injected, 75 min after endotoxin ad ministration. In saline-treated rabbits, MAP, aortic and portal vein b lood flow velocities remained steady but hepatic artery blood flow vel ocity decreased. Only N-omega-nitro-L-arginine (7.5 mg/kg, intravenous ly) significantly increased MAP compared to saline treatment. However, aortic, portal vein, and hepatic artery blood flow velocities were lo wer in rabbits treated with N-omega-nitro-L-arginine than in saline-tr eated rabbits. L-Arginine (600 mg/kg, intravenously) increased aortic blood flow and portal vein blood flow velocity with no change on hepat ic artery blood flow velocity. In contrast, linsidomine (1 mg) increas ed both hepatic flows. These results show that NO inhibition after end otoxin injection reduces systemic and liver flows, while NO release fr om linsidomine improves them. These findings question the usefulness o f NO inhibition during septic shock, particularly as hepatic failure f requently occurs in the evolution of the disease.