Hitomi Hirofumi, Fukui Toshiki, Moriwaki Kumiko, Matsubara Keisuke, Sun Guang-Ping, Rahman Matlubur, Nishiyama Akira, Kiyomoto Hideyasu, Kimura Shoji, Ohmori Koji, Abe Youichi, Kohno Masakazu
Division of Nephrology, Kagawa University Faculty of Medicine, Kita-gun, Kagawa, Japan.
J Hypertens. 2006 Jun;24(6):1089-95. doi: 10.1097/01.hjh.0000226199.51805.88.
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).
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.
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.
机械力和血管紧张素II影响血管细胞的结构和功能，并在活性氧生成中起重要作用。在本研究中，我们检测了机械牵张和血管紧张素II对大鼠血管平滑肌细胞（VSMC）中NADPH氧化酶的重要膜成分p22 - phox和Nox - 1表达以及超氧化物生成的影响。
单独的牵张力或血管紧张素II均未改变VSMC中p22 - phox和Nox - 1的表达。然而，联合刺激显著增加了p22 - phox和Nox - 1 mRNA，这与NADPH氧化酶活性增加、超氧化物生成以及总8 - 异前列腺素F2α浓度增加相关。血管紧张素I（AT1）受体拮抗剂RNH - 6270（100 nmol/l）处理可阻止牵张力与血管紧张素II联合诱导的p22 - phox mRNA水平升高。牵张力上调了AT1受体的蛋白表达。
这些数据表明机械牵张和血管紧张素II协同增加VSMC中NADPH氧化酶的表达，并提示该机制部分是通过机械牵张诱导的AT1受体上调介导的。机械应变和血管紧张素II的联合作用可能在高血压状态下通过超氧化物生成促进血管损伤。
