Journal
JOURNAL OF HYPERTENSION
Volume 38, Issue 4, Pages 765-773Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/HJH.0000000000002304
Keywords
5; 6 nephrectomy; afferent renal denervation; chronic kidney disease; hypertension; renal function; renin-angiotensin system
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Funding
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior - Brasil (CAPES) [001]
- Sao Paulo Research Foundation [FAPESP 18/02671-3]
- Brazilian National Research Council [CNPq 455537/2014-3, 0817/2018]
- FAPESP [17/03905-5, 13/23741-6]
- CAPES-PNPD postdoctoral fellowships
- CNPq
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Background: Clinical and experimental evidence have shown that renal denervation, by removing both the sympathetic and afferent nerves, improves arterial hypertension and renal function in chronic kidney disease (CKD). Given the key role of renal sympathetic innervation in maintaining sodium and water homeostasis, studies have indicated that the total removal of renal nerves leads to impaired compensatory mechanisms during hemodynamic challenges. Method: In the present study, we hypothesized that afferent (or sensory) fibers from the diseased kidney contribute to sympathetic overactivation to the kidney and other target organ, such as the splanchnic region, contributing to hypertension in CKD. We used a method to remove selectively the afferent renal fibers (periaxonal application of 33 mmol/l capsaicin) in a rat model of CKD, the 5/6 nephrectomy. Results: Three weeks after afferent renal denervation (ARD), we found a decrease in mean arterial pressure (similar to 15%) and normalization in renal and splanchnic sympathetic nerve hyperactivity in the CKD group. Interestingly, intrarenal renin--angiotensin system, as well as renal fibrosis and function and proteinuria were improved after ARD in CKD rats. Conclusion: The findings demonstrate that afferent fibers contribute to the maintenance of arterial hypertension and reduced renal function that are likely to be mediated by increased sympathetic nerve activity to the renal territory as well as to other target organs in CKD.
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