Abstract
Overexpression of DDAH‐1 in mice inhibits effects of ADMA on endothelial function in the cerebral circulation
The FASEB journal, Vol.20(4), pp.A731-A731
03/2006
DOI: 10.1096/fasebj.20.4.A731-a
Abstract
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of eNOS and increases in ADMA levels are associated with endothelial dysfunction and cardiovascular disease. ADMA is hydrolysed by the enzyme DDAH (dimethylarginine dimethylaminohydrolase). We tested the hypothesis that overexpression of human DDAH‐1 in transgenic mice (DDAH‐Tg) would inhibit the effects of ADMA on endothelial function. Using non‐transgenic (non‐Tg) and DDAH‐Tg mice, we compared responses of carotid arteries (in vitro) and cerebral arterioles (in vivo) to acetylcholine (ACh) and nitropruside (NP) in the presence or absence of ADMA. Responses of carotid arteries to ACh in DDAH‐Tg animals were slightly enhanced compared to non‐Tg mice (65±7 vs 57±6 % relaxation to 1 μM ACh respectively, p=0.04). ADMA (100 μM) impaired the response to ACh to a greater extent in non‐Tg compared to DDAH‐Tg mice (41±4 vs 50±10% respectively, P<0.05). Responses to NP were similar in all groups. In vivo, ADMA (10 μM) reduced responses of cerebral arterioles to ACh by 70% (31±5 vs 10±3%, respectively, P<0.05) in non‐Tg mice. This inhibitory effect was absent in DDAH‐Tg mice in which ACh dilated by 32±5 and 27±2% in the absence and presence of ADMA, respectively. These findings provide the first evidence that overexpression of DDAH‐1 protects against ADMA‐induced endothelial dysfunction.
Details
- Title: Subtitle
- Overexpression of DDAH‐1 in mice inhibits effects of ADMA on endothelial function in the cerebral circulation
- Creators
- Hayan Dayoub - Department of MedicineUniversity of Iowa2000 MLIowa CityIowa52242Cynthia Lynch - Department of MedicineUniversity of Iowa2000 MLIowa CityIowa52242Roman Rodionov - Department of MedicineUniversity of Iowa2000 MLIowa CityIowa52242John P. Cooke - Cardiovascular MedicineStanford University300 Pasteur DrStanfordCA94305Steven R. Lentz - University of IowaFrank M. Faraci - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.20(4), pp.A731-A731
- Publisher
- Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.20.4.A731-a
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Language
- English
- Date published
- 03/2006
- Academic Unit
- Cardiovascular Medicine; Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine; Neuroscience and Pharmacology
- Record Identifier
- 9984304741102771
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