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Articles in PresS, published online ahead of print August 21, 2001
Am J Physiol Renal Physiol, 10.1152/ajprenal.0039.2001
Submitted on February 8, 2001
Accepted on August 8, 2001
1 Surgery, Maastricht University, Maastricht, Netherlands
* To whom correspondence should be addressed. E-mail: mm.hallemeesch{at}ah.unimaas.nl.
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 as sepsis, 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 these mice. Female mice were injected i.p. with LPS, control mice received 0.9% NaCl. Six hours later, renal blood flow was measured using 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 was observed on renal nitric oxide production. In conclusion, increased renal de novo arginine production may serve to sustain systemic NO production. For the first time to our knowledge, it was shown that renal protein synthesis is enhanced in the early response to endotoxemia.
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