title: Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis.
abstract: Hydronephrosis is associated with the development of salt-sensitive hypertension. Studies have suggested that increased sympathetic nerve activity and oxidative stress play important roles in hypertension and the modulation of salt sensitivity. The present study primarily aimed to examine the role of renal sympathetic nerve activity in the development of hypertension in rats with hydronephrosis. In addition, we aimed to investigate if NADPH oxidase (NOX) function could be affected by renal denervation. Partial unilateral ureteral obstruction (PUUO) was created in 3-wk-old rats to induce hydronephrosis. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high-, and low-salt diets. The renal excretion pattern, NOX activity, and expression as well as components of the renin-angiotensin-aldosterone system were characterized after treatment with the normal salt diet. On the normal salt diet, rats in the PUUO group had elevated blood pressure compared with control rats (115 ± 3 vs. 87 ± 1 mmHg, P < 0.05) and displayed increased urine production and lower urine osmolality. The blood pressure change in response to salt loading (salt sensitivity) was more pronounced in the PUUO group compared with the control group (15 ± 2 vs. 5 ± 1 mmHg, P < 0.05). Renal denervation in PUUO rats attenuated both hypertension (97 ± 3 mmHg) and salt sensitivity (5 ± 1 mmHg, P < 0.05) and normalized the renal excretion pattern, whereas the degree of renal fibrosis and inflammation was not changed. NOX activity and expression as well as renin and ANG II type 1A receptor expression were increased in the renal cortex from PUUO rats and normalized by denervation. Plasma Na(+) and K(+) levels were elevated in PUUO rats and normalized after renal denervation. Finally, denervation in PUUO rats was also associated with reduced NOX expression, superoxide production, and fibrosis in the heart. In conclusion, renal denervation attenuates hypertension and restores the renal excretion pattern, which is associated with reduced renal NOX and components of the renin-angiotensin-aldosterone system. This study emphasizes a link between renal nerves, the development of hypertension, and modulation of NOX function.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden;
authors.forename: Maria
authors.initials: M
authors.lastname: Peleli
authors.affiliation: Division of Pediatric Surgery, Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden; Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden;
authors.forename: Ammar
authors.initials: A
authors.lastname: Al-Mashhadi
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden;
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden;
authors.forename: Erik
authors.initials: E
authors.lastname: Larsson
authors.affiliation: Department of Pediatric Surgery, Astrid Lindgren Hospital, Karolinska Institutet, Stockholm, Sweden; and.
authors.forename: Nils
authors.initials: N
authors.lastname: Wåhlin
authors.affiliation: Department of Physiology and Pharmacology, University of Southern Denmark, Odense, Denmark.
authors.forename: Boye L
authors.initials: BL
authors.lastname: Jensen
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden;
authors.forename: A Erik
authors.initials: AE
authors.lastname: G Persson
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; mattias.carlstrom@ki.se.
authors.forename: Mattias
authors.initials: M
authors.lastname: Carlström
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001794:Blood Pressure; D004195:Disease Models, Animal; D005355:Fibrosis; D006339:Heart Rate; D006869:Hydronephrosis / Q000201:enzymology* / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D006973:Hypertension / Q000201:enzymology / Q000208:ethnology / Q000235:genetics / Q000503:physiopathology / Q000601:surgery*; D007668:Kidney / Q000201:enzymology* / Q000294:innervation* / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D065667:Renal Elimination; D012084:Renin-Angiotensin System; D017673:Sodium Chloride, Dietary; D013562:Sympathectomy / Q000379:methods*; D014517:Ureteral Obstruction / Q000150:complications
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; D019255:NADPH Oxidases
keywords: NADPH oxidase 2; renal sympathetic nerves; renin-angiotensin-aldosterone system; renovascular hypertension; salt sensitivity