Role of endothelial Nox2 NADPH oxidase in angiotensin II-induced hypertension and vasomotor dysfunction

Murdoch, Colin E., Alom-Ruiz, Sara P., Wang, Minshu, Zhang, Min, Walker, Simon, Yu, Bin, Brewer, Alison and Shah, Ajay M. (2011). Role of endothelial Nox2 NADPH oxidase in angiotensin II-induced hypertension and vasomotor dysfunction. Basic Research in Cardiology, 106 (4), pp. 527-538.

Abstract

NADPH oxidase (Nox)-derived reactive oxygen species (ROS) are known to be involved in angiotensin II-induced hypertension and endothelial dysfunction. Several Nox isoforms are expressed in the vessel wall, among which Nox2 is especially abundant in the endothelium. Endothelial Nox2 levels rise during hypertension but little is known about the cell-specific role of endothelial Nox2 in vivo. To address this question, we generated transgenic mice with endothelial-specific overexpression of Nox2 (Tg) and studied the effects on endothelial function and blood pressure. Tg had an about twofold increase in endothelial Nox2 levels which was accompanied by an increase in p22phox levels but no change in levels of other Nox isoforms or endothelial nitric oxide synthase (eNOS). Basal NADPH oxidase activity, endothelial function and blood pressure were unaltered in Tg compared to wild-type littermates. Angiotensin II caused a greater increase in ROS production in Tg compared to wild-type aorta and attenuated acetylcholine-induced vasorelaxation. Both low and high dose chronic angiotensin II infusion increased telemetric ambulatory blood pressure more in Tg compared to wild-type, but with different patterns of BP change and aortic remodeling depending upon the dose of angiotensin II dose. These results indicate that an increase in endothelial Nox2 levels contributes to angiotensin II-induced endothelial dysfunction, vascular remodeling and hypertension.

Publication DOI: https://doi.org/10.1007/s00395-011-0179-7
Divisions: Life & Health Sciences > Biosciences
Aston Medical School
Additional Information: The Creative Commons Attribution (CC BY) license permits commercial and non-commercial re-use of an open access article, as long as the original author and source are properly attributed.
Uncontrolled Keywords: endothelium,vascular tone,NADPH oxidase,hypertension,reactive oxygen species
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Related URLs: http://www.scopus.com/inward/record.url?scp=79959704368&partnerID=8YFLogxK (Scopus URL)
Published Date: 2011-07
Authors: Murdoch, Colin E. ( 0000-0002-0274-819X)
Alom-Ruiz, Sara P.
Wang, Minshu
Zhang, Min
Walker, Simon
Yu, Bin
Brewer, Alison
Shah, Ajay M.

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License: Creative Commons Attribution


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