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

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 (cytochromec 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 in...