Back to Search
Start Over
Angiotensin II and NADPH oxidase increase ADMA in vascular smooth muscle cells.
- Source :
-
Hypertension (Dallas, Tex. : 1979) [Hypertension] 2010 Sep; Vol. 56 (3), pp. 498-504. Date of Electronic Publication: 2010 Aug 09. - Publication Year :
- 2010
-
Abstract
- Asymmetrical dimethylarginine inhibits nitric oxide synthase, cationic amino acid transport, and endothelial function. Patients with cardiovascular risk factors often have endothelial dysfunction associated with increased plasma asymmetrical dimethylarginine and markers of reactive oxygen species. We tested the hypothesis that reactive oxygen species, generated by nicotinamide adenine dinucleotide phosphate oxidase, enhance cellular asymmetrical dimethylarginine. Incubation of rat preglomerular vascular smooth muscle cells with angiotensin II doubled the activity of nicotinamide adenine dinucleotide phosphate oxidase but decreased the activities of dimethylarginine dimethylaminohydrolase by 35% and of cationic amino acid transport by 20% and doubled cellular (but not medium) asymmetrical dimethylarginine concentrations (P<0.01). This was blocked by tempol or candesartan. Cells stably transfected with p22(phox) had a 50% decreased protein expression and activity of dimethylarginine dimethylaminohydrolase despite increased promoter activity and mRNA. The decreased DDAH protein expression and the increased asymmetrical dimethylarginine concentration in p22(phox)-transfected cells were prevented by proteosomal inhibition. These cells had enhanced protein arginine methylation, a 2-fold increased expression of protein arginine methyltransferase-3 (P<0.05) and a 30% reduction in cationic amino acid transport activity (P<0.05). Asymmetrical dimethylarginine was increased from 6+/-1 to 16+/-3 micromol/L (P<0.005) in p22(phox)-transfected cells. Thus, angiotensin II increased cellular asymmetrical dimethylarginine via type 1 receptors and reactive oxygen species. Nicotinamide adenine dinucleotide phosphate oxidase increased cellular asymmetrical dimethylarginine by increasing enzymes that generate it, enhancing the degradation of enzymes that metabolize it, and reducing its cellular transport. This could underlie increases in cellular asymmetrical dimethylarginine during oxidative stress.
- Subjects :
- Analysis of Variance
Angiotensin II metabolism
Animals
Arginine genetics
Arginine metabolism
Benzimidazoles pharmacology
Biphenyl Compounds
Blotting, Western
Cells, Cultured
Muscle, Smooth, Vascular cytology
Muscle, Smooth, Vascular metabolism
Myocytes, Smooth Muscle metabolism
NADPH Oxidases genetics
Rats
Reactive Oxygen Species metabolism
Reverse Transcriptase Polymerase Chain Reaction
Tetrazoles pharmacology
Angiotensin II pharmacology
Arginine analogs & derivatives
Muscle, Smooth, Vascular drug effects
Myocytes, Smooth Muscle drug effects
NADPH Oxidases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4563
- Volume :
- 56
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Hypertension (Dallas, Tex. : 1979)
- Publication Type :
- Academic Journal
- Accession number :
- 20696982
- Full Text :
- https://doi.org/10.1161/HYPERTENSIONAHA.110.152959