King's College London

Research portal

Endothelial Nox4 NADPH Oxidase Enhances Vasodilatation and Reduces Blood Pressure lh Vivo

Student thesis: Doctoral ThesisDoctor of Philosophy

NADPH oxidases are major sources of reactive oxygen species (ROS) involved in the pathophysiology of many cardiovascular diseases, acting through the modulation of redox-sensitive signalling pathways as well as the inactivation of nitric oxide and generation of endothelial dysfunction. There are five oxidase isoforms (Nox1 - Nox5), which have different tissue distributions, are subject to stimulus-specific activation and may exert distinct downstream effects. Endothelial cells co-express two of these isoforms, the classical Nox isoform, Nox2, and a novel isoform, Nox4. Recent studies indicate that Nox4 generates predominantly hydrogen peroxide (H2O2) but its role in vivo remains unclear. To address this question, transgenic mice with endothelial-specific overexpression of Nox4 were studied as an approach to investigate the in vivo functional significance of Nox4 in the endothelium. Unexpectedly, Nox4 overexpression was found to significantly enhance acetylcholine-induced vasodilatation compared to wild-type littermates. This resulted from increased H2O2 production and not from altered nitric oxide bioavailability. Transgenic mice also had lower systemic blood pressure compared to wild-type littermates which was normalised by three structurally separate antioxidants. Endothelial Nox4 exerts potentially beneficial effects on vasodilator function and blood pressure that are attributable to H2O2 generation. These effects are quite distinct to those reported for Nox1 and Nox2 which involve superoxide-mediated inactivation of nitric oxide. These results suggest that therapeutic strategies to modulate ROS production in vascular disease may need to separately target individual Nox isoforms.
Original languageEnglish
Awarding Institution
Award date2012


Download statistics

No data available

View graph of relations

© 2018 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454