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Renal denervation attenuates hypertension and renal dysfunction in a model of cardiovascular and renal disease, which is associated with reduced NADPH and xanthine oxidase activity
Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery. Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..ORCID iD: 0000-0002-6002-6670
Karolinska Inst, Dept Med Biochem & Biophys, Div Physiol Chem 2, Stockholm, Sweden..
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2017 (English)In: Redox Biology, ISSN 0090-7324, E-ISSN 2213-2317, Vol. 13, p. 522-527Article in journal (Refereed) Published
Abstract [en]

Oxidative stress is considered a central pathophysiological event in cardiovascular disease, including hypertension. Early age reduction in renal mass is associated with hypertension and oxidative stress in later life, which is aggravated by increased salt intake. The aim of the present study was to examine if renal sympathetic denervation can exert blood pressure lowering effects in uninephrectomized (UNX) rats (3-week old) fed with high salt (HS, 4%; w/w) diet for 4 weeks. Moreover, we investigated if renal denervation is associated with changes in NADPH and xanthine oxidase-derived reactive oxygen species. Rats with UNX + HS had reduced renal function, elevated systolic and diastolic arterial pressures, which was accompanied by increased heart weight, and cardiac superoxide production compared to sham operated Controls. UNX + HS was also associated with higher expression and activity of NADPH and xanthine oxidase in the kidney. Renal denervation in rats with UNX + HS attenuated the development of hypertension and cardiac hypertrophy, but also improved glomerular filtration rate and reduced proteinuria. Mechanistically, renal de nervation was associated with lower expression and activity of both NADPH oxidase and xanthine oxidase in the kidney, but also reduced superoxide production in the heart. In conclusion, our study shows for the first time that renal denervation has anti-hypertensive, cardio- and reno-protective effects in the UNX + HS model, which can be associated with decreased NADPH oxidase- and xanthine oxidase-derived reactive oxygen species (i.e., superoxide and hydrogen peroxide) in the kidney.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV , 2017. Vol. 13, p. 522-527
Keywords [en]
Renal denervation, Xanthine oxidase, NADPH oxidase, Hypertension, Renal dysfunction, Cardiovascular disease
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-335129DOI: 10.1016/j.redox.2017.06.013ISI: 000410470000047PubMedID: 28734244OAI: oai:DiVA.org:uu-335129DiVA, id: diva2:1162228
Funder
Swedish Heart Lung Foundation, 20140448Swedish Research Council, 2016-01381The Karolinska Institutet's Research Foundation, 2415/2012-225, 2-3707/2013Available from: 2017-12-04 Created: 2017-12-04 Last updated: 2018-01-13Bibliographically approved

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