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Dimethylarginine dimethylaminohydrolase (DDAH): expression, regulation, and function in the cardiovascular and renal systems
- Source :
- American Journal of Physiology-Heart and Circulatory Physiology. 293:H3227-H3245
- Publication Year :
- 2007
- Publisher :
- American Physiological Society, 2007.
-
Abstract
- Asymmetric ( NG, NG)-dimethylarginine (ADMA) inhibits nitric oxide (NO) synthases (NOS). ADMA is a risk factor for endothelial dysfunction, cardiovascular mortality, and progression of chronic kidney disease. Two isoforms of dimethylarginine dimethylaminohydrolase (DDAH) metabolize ADMA. DDAH-1 is the predominant isoform in the proximal tubules of the kidney and in the liver. These organs extract ADMA from the circulation. DDAH-2 is the predominant isoform in the vasculature, where it is found in endothelial cells adjacent to the cell membrane and in intracellular vesicles and in vascular smooth muscle cells among the myofibrils and the nuclear envelope. In vivo gene silencing of DDAH-1 in the rat and DDAH +/− mice both have increased circulating ADMA, whereas gene silencing of DDAH-2 reduces vascular NO generation and endothelium-derived relaxation factor responses. DDAH-2 also is expressed in the kidney in the macula densa and distal nephron. Angiotensin type 1 receptor activation in kidneys reduces the expression of DDAH-1 but increases the expression of DDAH-2. This rapidly evolving evidence of isoform-specific distribution and regulation of DDAH expression in the kidney and blood vessels provides potential mechanisms for nephron site-specific regulation of NO production. In this review, the recent advances in the regulation and function of DDAH enzymes, their roles in the regulation of NO generation, and their possible contribution to endothelial dysfunction in patients with cardiovascular and kidney diseases are discussed.
- Subjects :
- medicine.medical_specialty
Endothelium
Physiology
Arginine
Kidney
Nitric Oxide
Gene Expression Regulation, Enzymologic
Amidohydrolases
Nitric oxide
chemistry.chemical_compound
Physiology (medical)
Internal medicine
Diabetes Mellitus
medicine
Animals
Humans
Endothelial dysfunction
Endothelium-Dependent Relaxing Factors
biology
business.industry
Liver Diseases
medicine.disease
Dimethylargininase
Isoenzymes
Vasodilation
Nitric oxide synthase
medicine.anatomical_structure
Endocrinology
chemistry
Cardiovascular Diseases
biology.protein
Kidney Diseases
Endothelium, Vascular
Nitric Oxide Synthase
Cardiology and Cardiovascular Medicine
Asymmetric dimethylarginine
business
Kidney disease
Subjects
Details
- ISSN :
- 15221539 and 03636135
- Volume :
- 293
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Heart and Circulatory Physiology
- Accession number :
- edsair.doi.dedup.....5b08bb51269df0a63a761ff2b5477feb
- Full Text :
- https://doi.org/10.1152/ajpheart.00998.2007