title: Endothelium-specific activation of NAD(P)H oxidase in aortas of exogenously hyperinsulinemic rats.
abstract: 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 micromol/l apocynin (an inhibitor of NADPH oxidase) or 10 micromol/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.
authors.affiliation: Third Department of Medicine, Shiga University of Medical Science, Seta, Otsu, Shiga 520-2192, Japan. kasiwagi@belle.shiga-med.ac.jp
authors.forename: A
authors.initials: A
authors.lastname: Kashiwagi
authors.forename: K
authors.initials: K
authors.lastname: Shinozaki
authors.forename: Y
authors.initials: Y
authors.lastname: Nishio
authors.forename: H
authors.initials: H
authors.lastname: Maegawa
authors.forename: Y
authors.initials: Y
authors.lastname: Maeno
authors.forename: A
authors.initials: A
authors.lastname: Kanazawa
authors.forename: H
authors.initials: H
authors.lastname: Kojima
authors.forename: M
authors.initials: M
authors.lastname: Haneda
authors.forename: H
authors.initials: H
authors.lastname: Hidaka
authors.forename: H
authors.initials: H
authors.lastname: Yasuda
authors.forename: R
authors.initials: R
authors.lastname: Kikkawa
mesh_terms: D000818:Animals; D001011:Aorta / Q000201:enzymology; D001794:Blood Pressure; D016503:Drug Delivery Systems; D004730:Endothelium, Vascular / Q000201:enzymology*; D005609:Free Radicals / Q000378:metabolism; D006946:Hyperinsulinism / Q000139:chemically induced / Q000378:metabolism*; D007004:Hypoglycemic Agents; D007328:Insulin; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D005609:Free Radicals; D007004:Hypoglycemic Agents; D007328:Insulin; D009097:Multienzyme Complexes; D013482:Superoxide Dismutase; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases