Renal arginine and protein synthesis are increased during early endotoxemia in mice

The kidney has an important function in arginine metabolism, because the kidney is the main endogenous source for de novo arginine production from circulating citrulline. In conditions such as sepsis, nitric oxide (NO) production is increased and is dependent on extracellular arginine availability. To elucidate the adaptive role of renal de novo arginine synthesis in a condition of increased NO production, we studied renal arginine metabolism in a mouse model of endotoxemia. Because arginine flux is largely dependent on protein flux, we also measured protein metabolism in mice. Female mice were injected intraperitoneally with lipopolysaccharide; control mice received 0.9% NaCl. Six hours later, renal blood flow was measured with the use of para-aminohippuric acid. Arginine and protein metabolism were studied using organ-balance, stable-isotope techniques. Systemic NO production was increased in the endotoxin-treated mice. In addition, renal protein synthesis and de novo arginine production from citrulline were increased. However, no effect on renal NO production was observed. In conclusion, increased renal de novo arginine production may serve to sustain systemic NO production. To our knowledge, it was shown for the first time that renal protein synthesis is enhanced in the early response to endotoxemia.