RENAL DENERVATION ATTENUATES NADPH OXIDASE-MEDIATED ...

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Articles in PresS. Am J Physiol Renal Physiol (November 4, 2015). doi:10.1152/ajprenal.00345.2015

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RENAL DENERVATION ATTENUATES NADPH OXIDASE-MEDIATED

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OXIDATIVE STRESS AND HYPERTENSION IN RATS WITH HYDRONEPHROSIS

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Maria Peleli1*, Ammar Al-Mashhadi2,3*, Ting Yang1, Erik Larsson4, Nils Wåhlin5, Boye L.

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Jensen6, A. Erik G. Persson3, Mattias Carlström1

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Dept of Physiology & Pharmacology, Karolinska Institutet, Stockholm, Sweden

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Dept of Women's and Children's Health, Div. of Pediatric Surgery, Uppsala University,

Sweden 3

Dept Medical Cell Biology, Uppsala University, Uppsala, Sweden

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Dept of Genetics and Pathology, Uppsala University, Uppsala, Sweden

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Department of Pediatric surgery, Astrid Lindgren hospital, Karolinska Institutet, Stockholm,

Sweden 6

Dept of Physiology & Pharmacology, University of Southern Denmark, Odense, Denmark

* Shared 1st authors

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Short title: Denervation attenuates oxidative stress & hypertension

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Word count (Full manuscript excl. Tables & Figure Legends): 6927

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Word count (Abstract): 250

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Tables: 2

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Figures: 7

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Correspondence:

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Mattias Carlström

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Dept. of Physiology and Pharmacology, Nanna Svartz Väg 2, S-17177, Stockholm, Sweden

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Phone: +46-(0)8-52487924

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Fax: +46-(0)8-332278

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E-mail: [email protected]

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1 Copyright © 2015 by the American Physiological Society.

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ABSTRACT

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Aim: Hydronephrosis is associated with development of salt-sensitive hypertension. Studies

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suggest that increased sympathetic nerve activity (SNA) and oxidative stress play important

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roles in hypertension and modulation of salt-sensitivity. This study primarily aimed to

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examine the role of renal SNA in the development of hypertension in rats with

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hydronephrosis. In addition, we aimed to investigate if NADPH oxidase (NOX) function

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could be affected by renal denervation.

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Methods: Partial unilateral ureteral obstruction (PUUO) was created in 3-weeks old rats to

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induce hydronephrosis. Sham surgery or renal denervation was performed at the same time.

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Blood pressure was measured during normal, high and low salt diets. Renal excretion pattern,

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NOX activity and expression, as well as components of renin-angiotensin-aldosterone-system

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(RAAS) were characterized after treatment with normal salt diet.

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Results: On normal salt diet, PUUO rats had elevated blood pressure compared with controls

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(115±3 vs 87±1 mmHg, p