title: Synergistic effect of mechanical stretch and angiotensin II on superoxide production via NADPH oxidase in vascular smooth muscle cells.
abstract: OBJECTIVE
  Mechanical forces and angiotensin II influence the structure and function of vascular cells, and play an important role in reactive oxygen species production. In this study, we examined the effects of mechanical stretch and angiotensin II on the expression of p22-phox and Nox-1, essential membrane components of NADPH oxidase, and superoxide production in rat vascular smooth muscle cells (VSMCs).
  
  
  RESULTS
  Neither a stretch force nor angiotensin II alone altered p22-phox and Nox-1 expression in VSMCs. Combined stimulation markedly increased p22-phox and Nox-1 mRNA, however, which was associated with increased NADPH oxidase activity, superoxide production and total 8-iso-prostaglandin F2alpha concentration. The increases in p22-phox mRNA levels induced by a stretch force in combination with angiotensin II were prevented by treatment with an angiotensin type I (AT1) receptor antagonist, RNH-6270 (100 nmol/l). Protein expression of the AT1 receptor was upregulated by a stretch force.
  
  
  CONCLUSIONS
  These data indicate that mechanical stretch and angiotensin II synergistically increase NADPH oxidase expression in VSMCs, and suggest that part of this mechanism is mediated through an upregulation of the AT1 receptor induced by mechanical stretch. The combined effects of mechanical strain and angiotensin II might promote vascular damage through the production of superoxide in a hypertensive state.
authors: Division of Nephrology, Kagawa University Faculty of Medicine, Kita-gun, Kagawa, Japan. hitomi@kms.ac.jp
authors: Hirofumi
authors: H
authors: Hitomi
authors: Toshiki
authors: T
authors: Fukui
authors: Kumiko
authors: K
authors: Moriwaki
authors: Keisuke
authors: K
authors: Matsubara
authors: Guang-Ping
authors: GP
authors: Sun
authors: Matlubur
authors: M
authors: Rahman
authors: Akira
authors: A
authors: Nishiyama
authors: Hideyasu
authors: H
authors: Kiyomoto
authors: Shoji
authors: S
authors: Kimura
authors: Koji
authors: K
authors: Ohmori
authors: Youichi
authors: Y
authors: Abe
authors: Masakazu
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authors: Kohno