Abstract
Asymmetric Dimethylarginine is a Paracrine Regulator of Vascular Function in CKD
Journal of cardiac failure, Vol.15(7 Suppl), pp.S181-S181
09/01/2009
DOI: 10.1016/j.cardfail.2009.07.148
Abstract
Background: Patients with chronic kidney disease (CKD) suffer increased morbidity and mortality from cardiovascular diseases (CVD). Asymmetric dimethylarginine (ADMA), an endogenous endothelial nitric oxide synthase (eNOS) inhibitor, is elevated in CKD. ADMA has been suggested to increase CVD in CKD, but direct evidence is missing. We assessed the effect of ADMA in endothelial function in CKD. Methods and Results: We created a CKD model by performing 5/6 nephrectomy (Nx) in mice. Samples were collected for measurements of renal function and ADMA, and NOx levels at 4 weeks after Nx. The serum ADMA level was higher (p < 0.01) in Nx mice (1.20 ± 0.05 nmol/mL) than in controls (1.00 ± 0.05 nmol/mL). Urinary NOx was lower in Nx mice (controls: 2153 ± 189 nmol/L, Nx mice: 706 ± 335 nmol/L, p < 0.05). Isometric tension study using aortic rings showed that endothelium-mediated relaxation induced by acetylcholine was impaired in Nx mice. Furthermore, pretreatment with exogenously administered ADMA at a serum concentration comparable to that in Nx mice reduced acetylcholine-induced relaxation in the aorta of controls. Western blotting showed the phosphorylated eNOS level of the aorta was lower in Nx mice than in controls, whereas eNOS levels were similar. Conclusions: Elevated levels of circulating ADMA appear to impair endothelial function by inhibiting eNOS activity in CKD. ADMA may thus have a triggering role in the vasculo-renal interaction in CKD.
Details
- Title: Subtitle
- Asymmetric Dimethylarginine is a Paracrine Regulator of Vascular Function in CKD
- Creators
- Hidemi Kajimoto - Kurume UniversityHisashi Kai - Kurume UniversitySuguru Yasuoka - Kurume UniversityHiroki Aoki - Kurume UniversityTakahiro Anegawa - Kurume UniversityTsutomu Imaizumi - Kurume University
- Resource Type
- Abstract
- Publication Details
- Journal of cardiac failure, Vol.15(7 Suppl), pp.S181-S181
- DOI
- 10.1016/j.cardfail.2009.07.148
- ISSN
- 1071-9164
- eISSN
- 1532-8414
- Publisher
- Elsevier Inc
- Language
- English; Japanese
- Date published
- 09/01/2009
- Academic Unit
- Cardiology; Stead Family Department of Pediatrics
- Record Identifier
- 9984961023702771
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