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(Hypertension. 2003;42:985.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Effect of Shear Stress on Asymmetric Dimethylarginine Release From Vascular Endothelial Cells

Tomohiro Osanai; Masayuki Saitoh; Satoko Sasaki; Hirofumi Tomita; Toshiro Matsunaga; Ken Okumura

From the Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan.

Correspondence to Tomohiro Osanai, MD, Second Department of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562 Japan. E-mail osanait{at}cc.hirosaki-u.ac.jp

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/cm². A dominant-negative mutant of IB kinase and troglitazone at 8 µmol/L, an activator of peroxisome proliferator–activated receptor , abolished the shear stress–induced increase in PRMT-1 gene expression in parallel with the blockade of nuclear factor (NF)-B translocation into the nucleus. The activity of dimethylarginine dimethylaminohydrolase, the degradation enzyme of ADMA, was unchanged after shear stress 15 dyne/cm² and was enhanced by 1.48±0.06-fold (P<0.05) by shear stress at 25 dyne/cm². The release of ADMA was increased by 1.64±0.10-fold (P<0.05) by shear stress at 15 dyne/cm² but was not affected by shear stress at 25 dyne/cm². These results indicate that shear stress enhances gene expression of PRMT-1 and ADMA release via activation of the NF-B pathway. Shear stress at higher magnitudes facilitates the degradation of ADMA, thus returning ADMA release levels to baseline.

Key Words: stress, mechanical • endothelium • gene expression • arginine • nitric oxide • nitric oxide synthase

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