The role of NOS2 and NOS3 in renal protein and arginine metabolism during early endotoxemia in mice

Y.C. Luiking, M.M. Hallemeesch, W.H. Lamers, N.E. Deutz*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Previously, we observed an enhanced renal protein synthesis and increased de novo arginine production in the early response to endotoxemia in wild-type Swiss mice (Hallemeesch et al, AJP 2002;282:F316-23). To establish whether these changes are regulated by nitric oxide (NO) synthesized by NOS2 and NOS3, we studied C57BL6/J wild type (WT), NOS2-deficient (NOS2(-/-)), and NOS3-deficient (NOS3(-/-)) mice under baseline (unstimulated) and LPS-treated conditions. Renal protein, amino-acid, and arginine metabolism were studied at the whole-body level and across the kidney by infusing the stable isotopes L-[phenyl-(2)H5]Phenylalanine, L-[phenyl-(2)H2]Tyrosine, L-[guanidine-(15)N2]Arginine, and L-[ureido-(13)C; (2)H2]Citrulline. Renal blood flow was measured using radioactive PAH extraction. Under baseline conditions, renal blood flow was significantly reduced in NOS2(-/-) mice (0.29 +/- 0.01 ml.10g body wt(-1).min(-1) vs. 0.48 +/- 0.07 ml.10g body wt(-1).min(-1) in WT (P<0.05), and de novo arginine production was lower in NOS2(-/-) mice. After LPS challenge, renal protein turnover and arginine production increased in all 3 groups (P<0.05), even though renal de novo arginine synthesis did not increase. The expected increase in renal citrulline production and disposal after LPS was not observed in NOS2(-/-) mice (P=0.06). Collectively, these data show that NOS2 is constitutively expressed in the kidney and remarkably functional as it affects renal blood flow and de novo arginine production under baseline conditions, and is important for the increase in renal citrulline turnover during endotoxemia. NOS3, in contrast, appears less important for renal metabolism. The increase in renal protein turnover during endotoxemia does not depend on NOS2 or NOS3 activity.
Original languageEnglish
Pages (from-to)F816-F822
JournalAmerican Journal of Physiology-Renal Physiology
Issue number4
Publication statusPublished - 1 Jan 2005

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