Afferent innervation of the ischemic kidney contributes to renal dysfunction in renovascular hypertensive rats
The ablation of renal nerves, by destroying both the sympathetic and afferent fibers, has been shown to be effective in lowering blood pressure in resistant hypertensive patients. However, experimental studies have reported that the removal of sympathetic fibers may lead to side effects, such as the impairment of compensatory cardiorenal responses during a hemodynamic challenge. In the present study, we evaluated the effects of the selective removal of renal afferent fibers on arterial hypertension, renal sympathetic nerve activity, and renal changes in a model of renovascular hypertension. After 4 weeks of clipping the left renal artery, afferent renal denervation (ARD) was performed by exposing the left renal nerve to a 33 mM capsaicin solution for 15 min. After 2 weeks of ARD, we found reduced MAP (~ 18%) and sympathoexcitation to both the ischemic and contralateral kidneys in the hypertensive group. Moreover, a reduction in reactive oxygen species was observed in the ischemic (76%) and contralateral (27%) kidneys in the 2K1C group. In addition, ARD normalized renal function markers and proteinuria and podocin in the contralateral kidney. Taken altogether, we show that the selective removal of afferent fibers is an effective method to reduce MAP and improve renal changes without compromising the function of renal sympathetic fibers in the 2K1C model. Renal afferent nerves may be a new target in neurogenic hypertension and renal dysfunction.
KeywordsSympathetic nervous system Renovascular hypertension Afferent renal denervation Proteinuria
Nathalia R. Lopes, Guiomar N. Gomes, Adriana C. Girardi, Fernando N. Nogueira, Ruy R. Campos, Cássia T. Bergamaschi, and Erika E. Nishi contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Nathalia R. Lopes, Maycon I. O. Milanez, Beatriz S. Martins, Amanda C. Veiga, Giovanna R. Ferreira, and Polliane M. Carvalho. The first draft of the manuscript was written by Nathalia R. Lopes and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001, by the São Paulo Research Foundation (FAPESP 18/02671-3 and 16/22140-7) and by the Brazilian National Research Council (CNPq 406233/2018-7, 0817/2018). NRL was a recipient of FAPESP scholarships (15/23858-6, 17/12383-2). RRC, ACCG, and CTB are recipients of the CNPq productive research fellowship.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
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