Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis

Autor: Erik G. Larsson, A. Erik G. Persson, Ammar Nadhom Farman Al-Mashhadi, Maria Peleli, Mattias Carlström, Nils Wåhlin, Ting Yang, Boye L. Jensen
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Physiology
Hypertension/enzymology
RNA
Messenger/metabolism
Blood Pressure
Hydronephrosis
Renal sympathetic nerves
030204 cardiovascular system & hematology
Kidney
medicine.disease_cause
Renovascular hypertension
Rats
Sprague-Dawley
Renin-Angiotensin System
0302 clinical medicine
Myocardium/enzymology
Heart Rate
Denervation
NADPH oxidase
biology
medicine.anatomical_structure
Salt sensitivity
Hypertension
Ureteral Obstruction
medicine.medical_specialty
Kidney/enzymology
03 medical and health sciences
Internal medicine
Renin–angiotensin system
medicine
Animals
RNA
Messenger
Sodium Chloride
Dietary
Sympathectomy
NADPH oxidase 2
business.industry
Myocardium
NADPH Oxidases/genetics
NADPH Oxidases
medicine.disease
Fibrosis
Disease Models
Animal
Oxidative Stress
Renal Elimination
030104 developmental biology
Blood pressure
Endocrinology
Renin-angiotensin-aldosterone system
biology.protein
Ureteral Obstruction/complications
Hydronephrosis/enzymology
Sympathectomy/methods
business
Biomarkers/blood
Biomarkers
Oxidative stress
Zdroj: Peleli, M, Al-Mashhadi, A, Yang, T, Larsson, E, Wåhlin, N, Jensen, B L, Persson, A E G & Carlström, M 2016, ' Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis ', American Journal of Physiology: Renal Physiology, vol. 310, no. 1, pp. F43-F56 . https://doi.org/10.1152/ajprenal.00345.2015
ISSN: 1522-1466
1931-857X
DOI: 10.1152/ajprenal.00345.2015
Popis: 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.
Databáze: OpenAIRE
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