Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Oct:13:522-527.
doi: 10.1016/j.redox.2017.06.013. Epub 2017 Jul 5.

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

Maria Peleli  1 , Peter Flacker  2 , Zhengbing Zhuge  1 , Cristina Gomez  3 , Craig E Wheelock  3 , A Erik G Persson  4 , Mattias Carlstrom  5
Affiliations

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

Maria Peleli et al. Redox Biol. 2017 Oct.

Abstract

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 denervation 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.

Keywords: Cardiovascular disease; Hypertension; NADPH oxidase; Renal denervation; Renal dysfunction; Xanthine oxidase.

PubMed Disclaimer

Figures

fx1
Graphical abstract
Fig. 1
Fig. 1
Systolic (A), diastolic (B), mean arterial pressure (C) and heart rate (D) in Control, UNX + HS and UNX + HS + RDN rats. Cardiac hypertrophy estimated as the total heart weight (E) and cardiac O2•− production (F). n = 7–10/group, *p < 0.05 vs. indicated group.
Fig. 2
Fig. 2
Total kidney weight (A), kidney function determined as eGFR (B), proteinuria (C) and urinary markers of oxidative stress, i.e., 11-dehydro TXB2/Creatinine (D), 8,12-iso-iPF2a-VI/ Creatinine (E) and 5-iPF2a-VI/Creatinine Ratio (F) in Control, UNX + HS and UNX + HS + RDN rats. n = 7–10/group for (A), n = 9–10/group for (B), n = 5–8/group for (C-E), *p < 0.05 vs. indicated group.
Fig. 3
Fig. 3
Renal NADPH oxidase-mediated H2O2 (A) and O2•− (B) production, as well as renal xanthine oxidase-mediated H2O2 (C) and O2•− (D) production in Control, UNX + HS and UNX + HS + RDN rats. n = 6–10/group, *p < 0.05 vs. indicated group.
Fig. 4
Fig. 4
Relative changes in p22phox mRNA (A) and protein (B) expression, as well as relative changes in xanthine oxidase mRNA (C) and protein (D) expression in kidneys from Control, UNX + HS and UNX + HS + RDN rats. n = 6–10/group for (A & C), n = 5–8/group for (B & D), *p < 0.05 vs. indicated group.
See this image and copyright information in PMC

References

    1. Carlstrom M., Sallstrom J., Skott O., Larsson E., Persson A.E. Uninephrectomy in young age or chronic salt loading causes salt-sensitive hypertension in adult rats. Hypertension. 2007;49:1342–1350. - PubMed
    1. Gossmann J., Wilhelm A., Kachel H.G., Jordan J., Sann U., Geiger H., Kramer W., Scheuermann E.H. Long-term consequences of live kidney donation follow-up in 93% of living kidney donors in a single transplant center. Am. J. Transplant. 2005;5:2417–2424. - PubMed
    1. Zoccali C., Mallamaci F. The salt epidemic: old and new concerns. Nutr. Metab. Cardiovasc. Dis. 2000;10:168–171. - PubMed
    1. Boudville N., Prasad G.V., Knoll G., Muirhead N., Thiessen-Philbrook H., Yang R.C., Rosas-Arellano M.P., Housawi A., Garg A.X., Donor N. Nephrectomy outcomes research, meta-analysis: risk for hypertension in living kidney donors. Ann. Intern. Med. 2006;145:185–196. - PubMed
    1. Meneton P., Jeunemaitre X., de Wardener H.E., MacGregor G.A. Links between dietary salt intake, renal salt handling, blood pressure, and cardiovascular diseases. Physiol. Rev. 2005;85:679–715. - PubMed

LinkOut - more resources