In:
Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 42, No. 5 ( 2003-11), p. 985-990
Abstract:
We demonstrated recently that plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase, are increased by high salt intake concomitantly with a decrease in plasma levels of NO in human hypertension. We investigated the effect of shear stress on ADMA release in 2 types of cells: transformed human umbilical vein endothelial cells (HUVECs; cell line ECV-304) and HUVECs. Exposure of ECV-304 cells and HUVECs to shear stress with the use of a cone-plate viscometer enhanced gene expression of protein arginine methyltransferase (PRMT-1), ADMA synthase. In HUVECs, the ratio of PRMT-1 to glyceraldehyde 3-phosphate dehydrogenase mRNA was increased by 2-fold by a shear stress of ≥15 dyne/cm 2 . A dominant-negative mutant of IκB kinase α and troglitazone at 8 μmol/L, an activator of peroxisome proliferator–activated receptor γ, abolished the shear stress–induced increase in PRMT-1 gene expression in parallel with the blockade of nuclear factor (NF)-κB translocation into the nucleus. The activity of dimethylarginine dimethylaminohydrolase, the degradation enzyme of ADMA, was unchanged after shear stress ≤15 dyne/cm 2 and was enhanced by 1.48±0.06-fold ( P 〈 0.05) by shear stress at 25 dyne/cm 2 . The release of ADMA was increased by 1.64±0.10-fold ( P 〈 0.05) by shear stress at 15 dyne/cm 2 but was not affected by shear stress at 25 dyne/cm 2 . These results indicate that shear stress enhances gene expression of PRMT-1 and ADMA release via activation of the NF-κB pathway. Shear stress at higher magnitudes facilitates the degradation of ADMA, thus returning ADMA release levels to baseline.
Type of Medium:
Online Resource
ISSN:
0194-911X
,
1524-4563
DOI:
10.1161/01.HYP.0000097805.05108.16
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2003
detail.hit.zdb_id:
2094210-2
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