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Am J Physiol Endocrinol Metab 277: E976-E983, 1999;
0193-1849/99 $5.00
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Vol. 277, Issue 6, E976-E983, December 1999

Endothelium-specific activation of NAD(P)H oxidase in aortas of exogenously hyperinsulinemic rats

Atsunori Kashiwagi, Kazuya Shinozaki, Yoshihiko Nishio, Hiroshi Maegawa, Yasuhiro Maeno, Akio Kanazawa, Hideto Kojima, Masakazu Haneda, Hideki Hidaka, Hitoshi Yasuda, and Ryuichi Kikkawa

Third Department of Medicine, Shiga University of Medical Science, Seta, Otsu, Shiga 520-2192, Japan

To examine the effects of chronic hyperinsulinemia on vascular tissues, we examined the production of superoxide anion (O-2) in the aortic tissues of control and exogenously hyperinsulinemic rats performed by the implantation of an insulin pellet for 4 wk. O-2 production by aortic segments from hyperinsulinemic rats was 2.4-fold (lucigenin chemiluminescence method) and 1.7-fold (cytochrome c method) of that of control rats without any differences in O-2 degrading activities in aortic tissues, respectively (P < 0.025). The increment was completely abolished in the presence of either 100 µmol/l apocynin (an inhibitor of NADPH oxidase) or 10 µmol/l diphenyleneiodonium (an inhibitor of flavin-containing enzyme) and was exclusively endothelium dependent. Consistently, NAD(P)H oxidase activities in endothelial homogenate in hyperinsulinemic rats were dose dependently stimulated above the values of control rats, although these activities in nonendothelial homogenate were not significantly stimulated by insulin. Furthermore, an insulin effect was also demonstrated 1 h after exposing aortic tissues to insulin. These results indicate that O-2 production specifically increases in endothelium of aortic tissues in chronic hyperinsulinemic rats through the activation of NAD(P)H oxidase.

oxidative stress; free radicals; endothelial cells


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