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This Article Full Text Full Text (PDF) All Versions of this Article: 295/2/F388    most recent 00405.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Huang, H.-S. Articles by Chen, J. Search for Related Content PubMed PubMed Citation Articles by Huang, H.-S. Articles by Chen, J.

Chronic L-arginine administration increases oxidative and nitrosative stress in rat hyperoxaluric kidneys and excessive crystal deposition

¹Department of Urology, National Taiwan University Hospital, Taiwan; ²School of Medicine, Fu Jen Catholic University, Hsinchuang, Taiwan; and ³Department of Urology, National Taiwan University Hospital, Yun-Lin Branch, Taipei, Taiwan, Republic of China

Submitted 31 August 2007 ; accepted in final form 26 April 2008

Hyperoxaluric kidneys show an impaired diuretic response to acute infusion of L-arginine. In this study, we examined the chronic effect of L-arginine supplementation on CaOx crystal formation in hyperoxaluric rat kidneys. Eight groups were tested: control (received drinking water), L group (received L-arginine, 0.6%), LN group [received N^G-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg)], L + LN group (received L-arginine + L-NAME), HP group [received hydroxyl-L-proline (HP, 5%) mixed with chow to induce hyperoxaluria], L + HP group (received HP + L-arginine), HP + LN group, and L + HP + LN group. The duration was 42 days, and each group had eight animals. Urinary biochemistry and renal CaOx amounts were measured, as well as renal expressions of nitric oxide synthase (NOS) isoforms and NAD(P)H oxidase. The distribution of inducible NOS (iNOS), NAD(P)H oxidase, ED1-positive cells, and nitrotyrosine was examined by immunohistochemical and immunofluorescence studies, whereas superoxide production from the kidneys was examined by fluorescence spectrometric assay. Compared with the HP group, the L + HP group had excessive CaOx crystal accumulation and enhanced endothelial NOS (eNOS), iNOS, and NAD(P)H oxidase protein expression in the kidney. Urinary excretion of nitrotyrosine was markedly increased. Increased superoxide formation in the L + HP kidney was derived from NAD(P)H oxidase and uncoupled eNOS, and increased nitrotyrosine formation might derive from iNOS and ED1-positive cells that gathered around the CaOx crystals. L-NAME cotreatment (L + HP + LN group) reduced renal oxidative nitrosative stress and tubular damage, which were induced by L + HP. The results showed that chronic L-arginine treatment to the hyperoxaluric kidney with massive CaOx crystal deposition may have a toxic effect by enhancing intrarenal oxidative and nitrosative stress.

hyperoxaluria; nephrolithiasis; NAD(P)H oxidase; nitric oxide synthase