Renal Deafferentation Prevents Progression of Hypertension and Changes to Sympathetic Reflexes in a Rabbit Model of Chronic Kidney Disease

Abstract

There is increasing evidence that renal denervation is effective in alleviating hypertension associated with elevation of renal sympathetic nerve activity (RSNA) in chronic kidney disease (CKD), but whether this is due to reduction in renal afferent signaling is unclear. We determined the cardiovascular and sympathetic effects of total renal denervation or afferent renal denervation (topical capsaicin) on CKD induced by glomerular layer lesioning of the left kidney and right nephrectomy in conscious rabbits. CKD increased blood pressure by 18±2 mmHg and plasma creatinine by 40% over 2 to 4 weeks (both P <0.001), while RSNA (43%) and total norepinephrine spillover (28%) were elevated in CKD compared with sham (both P =0.04). After total or afferent renal denervation blood pressure, RSNA and norepinephrine spillover were similar or lower than non-CKD (sham) rabbits. While plasma creatinine in CKD rabbits was not affected by total renal denervation, deafferented rabbits had lower levels ( P =0.017). The greater hypotensive response to pentolinium in CKD was also normalized after total or afferent denervation. Heart rate and RSNA baroreflex gain were similar in all groups. The RSNA response to airjet stress was greater in CKD compared with sham but not after total or afferent renal denervation. By contrast, the sympathetic response to hypoxia was similar in sham and CKD intact or deafferented groups but elevated in total denervated CKD animals. We conclude that the elevated sympathetic activity and blood pressure in this model of CKD is predominantly driven by renal afferents.

Effects of Renal Denervation on the Enhanced Renal Vascular Responsiveness to Angiotensin II in High-Output Heart Failure: Angiotensin II Receptor Binding Assessment and Functional Studies in Ren-2 Transgenic Hypertensive Rats

“…Therefore, the beneficial actions of our RDN might depend on the ablation of afferent renal nerves, which could explain the lack of actions of our RDN technique on the RBF in ACF TGR. This notion is supported by recent findings showing that selective targeting of the “Kidney-Brain Neural Axis” substantially attenuated hypertension and end-organ damage in 2K1C hypertensive rats and in the rabbit model of CKD [ 66 , 67 ]. Therefore, to test our new hypothesis it is necessary to examine the effects of selective ablation of renal sensory nerves on the course of HF in ACF TGR, e.g., using periaxonal capsaicin administration, a method developed originally by Foss et al [ 68 ].…”

Impact of Renal Denervation on Urinary Peptide-Based Biomarkers in Hypertension

“…17 Additionally, CKD273 can detect molecular changes associated with CKD at an early stage. 5,28 It is well established that an increased sympathetic nervous system activity contributes to hypertension in CKD, 29 and pharmacological BP-lowering has been shown to slow CKD progression. 30 Against this background, RDN is currently under investigation as an additional treatment option for patients with hypertension and CKD.…”

Renal denervation: recent developments in clinical and preclinical research

“…Beyond hypertension, renal denervation [23] and afferent denervation [24] were found to be renoprotective in a rabbit chronic kidney disease model. In a rat model of polycystic kidney disease, elevated afferent renal nerve activity was observed at baseline and afferent or total denervation attenuated cystogenesis [25].…”