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 sepsis is unknown. To answer this question, we studied the effects of L-arginine (the substrate for the NO synthase), linsidomine (a direct NO 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, 400 micrograms each). After endotoxin administration, and without fluid resuscitation, rabbits showed a hypodynamic shock with decrease in mean arterial pressure (MAP) and aortic blood flow velocity. Portal vein blood flow velocity decreased, whereas hepatic artery blood flow velocity increased. Saline or treatments were injected, 75 min after endotoxin administration. In saline-treated rabbits, MAP, aortic and portal vein blood flow velocities remained steady but hepatic artery blood flow velocity decreased. Only N omega-nitro-L-arginine (7.5 mg/kg, intravenously) significantly increased MAP compared to saline treatment. However, aortic, portal vein, and hepatic artery blood flow velocities were lower in rabbits treated with N omega-nitro-L-arginine than in saline-treated rabbits. L-Arginine (600 mg/kg, intravenously) increased aortic blood flow and portal vein blood flow velocity with no change on hepatic artery blood flow velocity. In contrast, linsidomine (1 mg) increased both hepatic flows. These results show that NO inhibition after endotoxin injection reduces systemic and liver flows, while NO release from linsidomine improves them. These findings question the usefulness of NO inhibition during septic shock, particularly as hepatic failure frequently occurs in the evolution of the disease.
Pastor
C M
CM
Department of Anesthesiology and Intensive Care, Lariboisière Hospital, Paris, France.
Payen
D M
DM
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D006499:Hepatic Artery / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019335:Nitroarginine; D011169:Portal Vein / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D011817:Rabbits; D012772:Shock, Septic / Q000503:physiopathology*; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D019335:Nitroarginine; D009569:Nitric Oxide; C002385:linsidomine; D001120:Arginine; D008981:Molsidomine