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.

Tumor Necrosis Factor-α Increases Airway Smooth Muscle Oxidants Production through a NADPH Oxidase-like System to Enhance Myosin Light Chain Phosphorylation and Contractility

“…However, the TNF-induced ROS production was significantly reduced by pretreatment with DPI (10 M) an inhibitor of flavincontaining enzymes such as NADPH oxidase (26) or by the NADPH oxidase inhibitor apocynin (10 M) (27,28). Furthermore, in separate experiments, we confirmed the effect of DPI by adding this agent 30 min after TNF.…”

“…Furthermore, we demonstrate that the NADPH oxidase complex was the main source of ROS in ASM cells under TNF stimulation. Indeed, incubation of ASM cells with two structurally different pharmacological inhibitors of NADPH oxidase (DPI (26) and apocynin (27,28)) significantly reduced TNFinduced ROS production, while the substrate NADPH significantly increased it. Moreover, inhibitors of mitochondrial respiratory chain, NO synthase, cyclooxygenase, and xanthine oxidase had no effect on TNF-induced ROS production.…”

Effect of the Angiotensin II Receptor Antagonist Telmisartan on Lipoprotein Lipase Mass in Preheparin Serum

“…Insulin resistance is known to affect the physiology of various organs, including skeletal muscles, adipose tissue and liver. Furthermore, recent basic and clinical studies have described the direct effects of insulin resistance at the level of the vessel wall [37][38][39][40] . LpL is known to exist in endothelial cells, showing activity, and LpL was also reported to exist on the coronary lumen surface 41) .…”

Relationship between Metabolic Syndrome and Early Stage Coronary Atherosclerosis

“…Recently, insulin resistance was reported to affect not only skeletal muscle and the liver but also vessel walls [31][32][33][34][35] . Kashiwagi A et al [36][37][38][39] reported that insulin resistance/hyperinsulinemia causes endothelial dysfunction and smooth muscle cell proliferation through the pathway of oxidative stress or inflammation, and consequently insulin resistance promotes atherosclerosis. In this study, there was a significant relationship between HOMA-IR as a marker of insulin resistance and percent plaque volume; however, multivariate analysis revealed that HOMA-IR did not select independent variables for percent plaque volume.…”