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Expression of NG,NG-dimethylarginine dimethylaminohydrolase and protein arginine N-methyltransferase isoforms in diabetic rat kidney: effects of angiotensin II receptor blockers
University of Tokyo, Japan and Georgetown University, USA .
University of Tokyo, Japan.
University College London, UK.
University of Tokyo, Japan.
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2008 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 57, no 1, 172-180 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: The nitric oxide (NO) synthase inhibitor asymmetric dimethylarginine (ADMA) is generated by protein arginine N-methyltransferase (PRMT)-1 and is metabolized by N(G),N(G)-dimethylarginine dimethylaminohydrolase (DDAH). We tested the hypothesis that increased serum ADMA (S(ADMA)) in the streptozotocin (STZ)-induced diabetic rat model of diabetes is mediated by an angiotensin receptor blocker-sensitive change in DDAH or PRMT expression.

RESEARCH DESIGN AND METHODS: Data were compared from four groups of rats: sham-injected controls, untreated STZ-induced diabetic rats at 4 weeks, STZ-induced diabetic rats administered the angiotensin II (Ang II) receptor blocker telmisartan for 2 weeks, and control rats administered telmisartan for 2 weeks.

RESULTS: Immunostaining and Western blotting of microdissected nephron segments localized DDAH I in the proximal tubules and DDAH II in the glomeruli, afferent arterioles, macula densa, and distal nephron. Renal Ang II and S(ADMA) increased with diabetes but were normalized by 2 weeks of telmisartan. DDAH I expression was decreased in diabetic kidneys, while DDAH II expression was increased. These changes were reversed by telmisartan, which also reduced expression of PRMT-1 and -5. Telmisartan increased expressions of DDAH I but decreased DDAH II in Ang II-stimulated kidney slices ex vivo.

CONCLUSIONS: Renal Ang II and S(ADMA) are increased in insulinopenic diabetes. They are normalized by an Ang II receptor blocker, which increases the renal expression of DDAH I, decreases PRMT-1, and increases renal NO metabolites.

Place, publisher, year, edition, pages
American Diabetes Association , 2008. Vol. 57, no 1, 172-180 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-99787DOI: 10.2337/db06-1772PubMedID: 17909098OAI: diva2:658176
Available from: 2013-10-21 Created: 2013-10-21 Last updated: 2013-10-29Bibliographically approved

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Palm, Fredrik
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