Synergistic effect of mechanical stretch and angiotensin II on superoxide production via NADPH oxidase in vascular smooth muscle cells.
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.
Hitomi
Hirofumi
H
Division of Nephrology, Kagawa University Faculty of Medicine, Kita-gun, Kagawa, Japan. hitomi@kms.ac.jp
Fukui
Toshiki
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Moriwaki
Kumiko
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Matsubara
Keisuke
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Sun
Guang-Ping
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Rahman
Matlubur
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Nishiyama
Akira
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Kiyomoto
Hideyasu
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Kimura
Shoji
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Ohmori
Koji
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Abe
Youichi
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Kohno
Masakazu
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