Complex reinnervation pattern after unilateral renal denervation in rats

Abstract

Renal denervation (DNX) is a treatment for resistant arterial hypertension. Efferent sympathetic nerves regrow, but reinnervation by renal afferent nerves has only recently been shown in the renal pelvis of rats after unilateral DNX. We examined intrarenal perivascular afferent and sympathetic efferent nerves after unilateral surgical DNX. Tyrosine hydroxylase (TH), CGRP, and smooth muscle actin were identified in kidney sections from 12 Sprague-Dawley rats, to distinguish afferents, efferents, and vasculature. DNX kidneys and nondenervated kidneys were examined 1, 4, and 12 wk after DNX. Tissue levels of CGRP and norepinephrine (NE) were measured with ELISA and mass spectrometry, respectively. DNX decreased TH and CGRP labeling by 90% and 95%, respectively (P < 0.05) within 1 wk. After 12 wk TH and CGRP labeling returned to baseline with a shift toward afferent innervation (P < 0.05). Nondenervated kidneys showed a doubling of both labels within 12 wk (P < 0.05). CGRP content decreased by 72% [3.2 ± 0.3 vs. 0.9 ± 0.2 ng/gkidney; P < 0.05] and NA by 78% [1.1 ± 0.1 vs. 0.2 ± 0.1 pmol/mgkidney; P < 0.05] 1 wk after DNX. After 12 wk, CGRP, but not NE, content in DNX kidneys was fully recovered, with no changes in the nondenervated kidneys. The use of phenol in the DNX procedure did not influence this result. We found morphological reinnervation and transmitter recovery of afferents within 12 wk after DNX. Despite morphological evidence of sympathetic regrowth, NE content did not fully recover. These results suggest a long-term net surplus of afferent influence on the DNX kidney may be contributing to the blood pressure lowering effect of DNX.

Reduced Renal Mass, Salt-Sensitive Hypertension Is Resistant to Renal Denervation

“…In the present study, these were unlikely cofounders as we used a standard surgical–pharmacological approach for extensive RDNx and showed that renal tissue norepinephrine levels at the end of the study were at an accepted level of suppression (<90% of control animals) for interruption of functional responses. Furthermore, and consistent with our findings, morphological evidence of nerve regrowth is not accompanied by an increase of renal norepinephrine content in rats, at least until 12 weeks post-denervation, well beyond the timeframe of our study ( Rodionova et al, 2016 ).…”

Neurogenic tachykinin mechanisms in experimental nephritis of rats

“…A close relationship of SP-positive nerve fibers to afferent and efferent arterioles and glomeruli was already described more than three decades ago [47]. We could confirm this finding with respect to SP [13,48]. However, such an interaction must not necessarily occur in the kidney since peptides like SP could be secreted along the whole surface of the axon and not only at the nerve endings [58].…”

“…Renal denervation reduced concentrations of SP in the respective kidneys to hardly detectable levels 7 days after the procedure pointing to neurogenic sources of SP [ 48 ]. Interestingly, the cellular distribution of the primary receptor for SP in the kidney has so far not raised too much attention.…”

“…All components of the immune system and of visceral organs are innervated by the autonomous nervous system [ 24 , 39 ]. In the kidney, the vessels, the glomeruli, the tubules, juxtaglomerular cells, and the renal pelvis are innervated by efferent sympathetic and afferent peptidergic nerves [ 32 , 48 , 58 ].…”

Effects of renal denervation on blood-pressure response to hemorrhagic shock in spontaneously hypertensive rats

“…In normotensive rats, reinnervation of the afferent renal sensory nerves and the efferent renal sympathetic nerves occurs over the same time course, both being complete at 9–12 weeks after RD. 35 Similarly, report of Booth et al 36 showed the reinnervation of renal afferent and efferent nerves at 5.5 months after catheter-based radiofrequency renal denervation in sheep and by 11 months the functional afferent and efferent responses to electric stimulation were normal.…”