uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Expression of DDAH and PRMT isoforms in the diabetic rat kidney; effects of angiotensin II receptor blocker
Show others and affiliations
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 NG, NG-dimethylarginine dimethylaminohydrolase (DDAH). We tested the hypothesis that increased serum ADMA (SADMA) in the streptozotocin (STZ)-induced rat model of diabetes mellitus (DM) is mediated by an angiotensin receptor blocker– sensitive change in DDAH or PRMT expression.

Research design and Methods: Data were compared from 4 groups of rats: sham injected controls; untreated STZ- DM at 4 weeks; STZ-DM rats administered the angiotensin II receptor blocker telmisartan for 2 weeks; 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 angiotensin II and SADMA increased with DM but were normalized by 2 weeks of telmisartan. DDAH I expression was decreased in DM 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.

Conclusion: Renal angiotensin II and SADMA are increased in insulinopenic DM. They are normalized by an angiotensin II receptor blocker which increases the renal expression of DDAH I, decreases PRMT-1 and increases renal NO metabolites.

Place, publisher, year, edition, pages
2008. Vol. 57, no 1, 172-180 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-11924DOI: 10.2337/db06-1772PubMedID: 17909098OAI: oai:DiVA.org:uu-11924DiVA: diva2:39693
Available from: 2008-01-21 Created: 2008-01-21 Last updated: 2010-04-19Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=17909098&dopt=Citation

Search in DiVA

By author/editor
Palm, Fredrik
By organisation
Department of Medical Cell Biology
In the same journal
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 239 hits
ReferencesLink to record
Permanent link

Direct link