Renal redox-sensitive signaling, but not blood pressure, is attenuated by Nox1 knockout in Angiotensin II-dependent chronic hypertension

Yogi, A., Mercure, C., Touyz, J., Callera, G.E., Montezano, A.C., Aranha, A.B., Tostes, R.C., Reudelhuber, T. and Touyz, R.M. (2008) Renal redox-sensitive signaling, but not blood pressure, is attenuated by Nox1 knockout in Angiotensin II-dependent chronic hypertension. Hypertension, 51(2), pp. 500-506. (doi: 10.1161/HYPERTENSIONAHA.107.103192)

Abstract

We demonstrated previously that, in mice with chronic angiotensin II–dependent hypertension, gp91phox-containing NADPH oxidase is not involved in the development of high blood pressure, despite being important in redox signaling. Here we sought to determine whether a gp91phox homologue, Nox1, may be important in blood pressure elevation and activation of redox-sensitive pathways in a model in which the renin-angiotensin system is chronically upregulated. Nox1-deficient mice and transgenic mice expressing human renin (TTRhRen) were crossed, and 4 genotypes were generated: control, TTRhRen, Nox1-deficient, and TTRhRen Nox1-deficient. Blood pressure and oxidative stress (systemic and renal) were increased in TTRhRen mice (P<0.05). This was associated with increased NADPH oxidase activation. Nox1 deficiency had no effect on the development of hypertension in TTRhRen mice. Phosphorylation of c-Src, mitogen-activated protein kinases, and focal adhesion kinase was significantly increased 2- to 3-fold in kidneys from TTRhRen mice. Activation of c-Src, p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and focal adhesion kinase but not of extracellular signal regulated kinase 1/2 or extracellular signal regulated kinase 5, was reduced in TTRhRen/Nox1-deficient mice (P<0.05). Expression of procollagen III was increased in TTRhRen and TTRhRen/Nox1-deficient mice versus control mice, whereas vascular cell adhesion molecule-1 was only increased in TTRhRen mice. Our findings demonstrate that, in Nox1-deficient TTRhRen mice, blood pressure is elevated despite reduced NADPH oxidase activation, decreased oxidative stress, and attenuated redox signaling. Our results suggest that Nox1-containing NADPH oxidase plays a key role in the modulation of systemic and renal oxidative stress and redox-dependent signaling but not in the elevation of blood pressure in a model of chronic angiotensin II–dependent hypertension.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Montezano, Dr Augusto and Touyz, Professor Rhian
• Authors: Yogi, A., Mercure, C., Touyz, J., Callera, G.E., Montezano, A.C., Aranha, A.B., Tostes, R.C., Reudelhuber, T., and Touyz, R.M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Hypertension
• ISSN: 0194-911X
• ISSN (Online): 1524-4563
• Published Online: 14 January 2008