Enhanced p47 phox NADPH sub‐unit expression impairs conductance and resistance vascular function in obese mice

Abstract

Metabolic disease is associated with vascular complication. However, the direct contribution and role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p47phox in obesity-induced vascular dysfunction is not fully determined. Thus, p47phox-/- and control mice were fed with high fat diet (HFD) for three months. Systolic blood pressure was normal in all groups. HFD increased body weight similarly in all groups; however, blood glucose was significantly increased in control mice compared to p47phox-/- mice. Insulin induced vascular reactivity was significantly impaired in control mice when fed with HFD but not affected in p47phox-/- mice. Vascular contraction in response to phenylephrine was not affected in all groups. Vascular endothelium-dependent relaxation (EDR) was impaired in control group fed with HFD but protected in p47phox-/- mice fed with HFD. The improvement of vascular function was associated with the rescue of eNOS and Akt signaling, and reduction in NOX2 and NOX4 mRNA levels and NADPH oxidase activity. The present study determines that HFD impairs vascular function through the augmented expression and activity of NADPH oxidase subunit p47phox. Therefore, p47phox could be an important target to improve vascular function in metabolic syndrome.