L-Arginine supplementation in hyperdynamic endotoxemic pigs: Effect on nitric oxide synthesis by the different organs

Objectives: Under septic conditions, the protective role of nitric oxide in the organs may become compromised at a time of increased demand as a result of decreased availability of L-arginine. It remains unknown whether supplementation with L-arginine, as a substrate, can modulate organ nitric oxide production. Design: Controlled study with laboratory animals. Setting: University research laboratory. Subjects: Female crossbred pigs. Intervention: Pigs were challenged with Escherichia coli endotoxin (intravenously) and received intravenous fluid resuscitation for 24 hrs to reproduce a model of long-lasting hyperdynamic endotoxemia. Pigs were infused with either L-arginine or L-alanine intravenously during endotoxin and via the intragastric route after cessation of endotoxin infusion. The effects Of L-arginine supplementation on nitric oxide synthesis and the relationships with arginine metabolism were determined with a stable isotope infusion protocol. Also, organ nitrite plus nitrate fluxes were measured. Implantation of multiple catheters enabled in vivo measurements across the hindquarter muscle, the portal-drained viscera, the liver, and the kidneys. Measurements and Results: The isotope conversion method showed that L-arginine intervention significantly increased nitric oxide production by the portal-drained viscera, liver, and kidneys, resulting in elevated whole-body nitric oxide synthesis under endotoxemic and postendotoxemic conditions. Organ nitrite plus nitrate fluxes only tended to increase because of high variance among data. Conclusions: In this endotoxemia model, supplemental use of L-arginine favored nitric oxide synthesis in various organs.