A Novel Catheter-Based Method for Denervation of Afferent Renal Nerves in Sheep

Catheter-based total renal denervation (TRDN) has recently gained FDA approval to lower blood pressure in patients with treatment-resistant hypertension. Current TRDN technologies indiscriminately destroy efferent (sympathetic) and afferent (sensory) renal nerves. However, preclinical studies suggest that the beneficial effects of TRDN may be due to ablation of afferent, rather than efferent, renal nerves. We developed a novel method for chemical ablation of afferent renal nerves by periaxonal application of capsaicin which has been employed in mouse and rat models of hypertension. In certain rodent models afferent-specific renal denervation (ARDN) has been shown to lower arterial pressure to the same degree as TRDN. The objective of the present study was to develop a catheter-based method for ARDN in a large animal model with the long-term goal of translating this treatment to humans. We tested the feasibility of using the Peregrine™ catheter infusion system, currently used to perform TRDN in humans by injection of ethanol, to perform catheter-based afferent renal denervation in sheep by periaxonal application of capsaicin.

Castrated, adult, male, Friesen sheep underwent Sham RDN (saline, n = 2), TRDN (ethanol, n = 4), or ARDN (capsaicin, n = 4) with the Peregrine™ catheter before termination > 2 weeks after the procedure. Denervation of renal efferents was verified by measurement of renal cortical norepinephrine (NE) content and anti-tyrosine hydroxylase (TH) staining; denervation of renal afferents was verified with anti-calcitonin gene-related peptide (CGRP) staining.

There was a significant decrease in TH + and CGRP + fibers in TRDN kidneys and in CGRP + but not TH + fibers in ARDN kidneys. TRDN significantly reduced renal cortical norepinephrine (NE) content by 89% while ARDN had similar NE content to Sham RDN kidneys.

This study establishes the feasibility of performing catheter-based afferent renal denervation in a large animal model. Furthermore, this study provides a translational model to evaluate catheter-based ARDN as a potential treatment for hypertension.