Journal article
Inhibition of eNOS phosphorylation mediates endothelial dysfunction in renal failure: new effect of asymmetric dimethylarginine
Kidney international, Vol.81(8), pp.762-768
04/01/2012
DOI: 10.1038/ki.2011.476
PMID: 22297680
Abstract
Patients with chronic kidney disease have elevated circulating asymmetric dimethylarginine (ADMA). Recent studies have suggested that ADMA impairs endothelial nitric oxide synthase (eNOS) by effects other than competition with the substrate L-arginine. Here, we sought to identify the molecular mechanism by which increased ADMA causes endothelial dysfunction in a chronic kidney disease model. In wild-type mice with remnant kidney disease, blood urea nitrogen, serum creatinine, and ADMA were increased by 2.5-, 2-, and 1.2-fold, respectively, without any change in blood pressure. Nephrectomy reduced endothelium-dependent relaxation and eNOS phosphorylation at Ser1177 in isolated aortic rings. In transgenic mice overexpressing dimethylarginine dimethylaminohydrolase-1, the enzyme that metabolizes ADMA, circulating ADMA was not increased by nephrectomy and was decreased to half that of wild-type mice. These mice did not exhibit the nephrectomy-induced inhibition of both endothelium-dependent relaxation and eNOS phosphorylation. In cultured human endothelial cells, agonist-induced eNOS phosphorylation and nitric oxide production were decreased by ADMA at concentrations less than that of L-arginine in the media. Thus, elevated circulating ADMA may be a cause, not an epiphenomenon, of endothelial dysfunction in chronic kidney disease. This effect may be attributable to inhibition of eNOS phosphorylation.
Details
- Title: Subtitle
- Inhibition of eNOS phosphorylation mediates endothelial dysfunction in renal failure: new effect of asymmetric dimethylarginine
- Creators
- Hidemi Kajimoto - Kurume UniversityHisashi Kai - Kurume UniversityHiroki Aoki - Kurume UniversitySuguru Yasuoka - Kurume UniversityTakahiro Anegawa - Kurume UniversityYuji Aoki - Kurume UniversitySeiji Ueda - Kurume UniversitySeiya Okuda - Kurume UniversityTsutomu Imaizumi - Kurume University
- Resource Type
- Journal article
- Publication Details
- Kidney international, Vol.81(8), pp.762-768
- DOI
- 10.1038/ki.2011.476
- PMID
- 22297680
- NLM abbreviation
- Kidney Int
- ISSN
- 0085-2538
- eISSN
- 1523-1755
- Publisher
- Elsevier Inc
- Number of pages
- 7
- Language
- English
- Date published
- 04/01/2012
- Academic Unit
- Cardiology; Stead Family Department of Pediatrics
- Record Identifier
- 9984961029102771
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