1. 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
- Author
-
Peleli, Maria, Flacker, Peter, Zhuge, Zhengbing, Gomez, Cristina, Wheelock, Craig E., Persson, Erik, and Carlstrom, Mattias
- Subjects
Xanthine Oxidase ,Hypertension, Renal ,RDN, renal denervation ,Crea, creatinine ,Cell- och molekylärbiologi ,Short Communication ,TBP, TATA-binding protein ,SDMA, symmetrical dimethylarginine ,Blood Pressure ,Cardiomegaly ,Kidney ,ROS, reactive oxygen species ,phox, phagocytic oxidase ,Animals ,Xanthine oxidase ,lcsh:QH301-705.5 ,bpm, beats per minute ,UNX, uninephrectomy ,MDA, malondialdehyde ,lcsh:R5-920 ,NADPH oxidase ,HS, high salt ,Myocardium ,eGFR, estimated glomerular filtration rate ,ADMA, asymmetrical dimethylarginine ,Heart ,NADPH, nicotinamide adenine dinucleotide phosphate ,TXB2, 11-dehydro-thromboxane B2 ,Cardiovascular disease ,Denervation ,NOX, NADPH oxidase ,Rats ,XOR, xanthine oxidoreductase ,lcsh:Biology (General) ,5-iPF2a-VI, 5-prostagladin F2a-VI ,8,12-iso-iPF2a-VI, 12-iso−5(R), 6E, 14Z-prostagladin F2a ,H2O2, hydrogen peroxide ,Hypertension ,Renal denervation ,Renal dysfunction ,lcsh:Medicine (General) ,Reactive Oxygen Species ,Cell and Molecular Biology ,NADP ,Glomerular Filtration Rate ,O2•−, superoxide - 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., Graphical abstract fx1, Highlights • Uninephrectomy + high salt intake (UNX + HS) is linked with hypertension and renal dysfunction. • UNX + HS increases renal NADPH oxidase-mediated O2•− and H2O2 production. • UNX + HS increases renal xanthine oxidase-mediated H2O2 production. • Renal denervation attenuates development of hypertension and renal dysfunction. • Renal denervation is associated with lower NADPH and xanthine oxidase activity.
- Published
- 2017