Complex Re-Innervation Pattern After Unilateral Renal Denervation in Rats Journal Article

Authors: Rodionova, K.; Fiedler, C.; Guenther, F.; Grouzmann, E.; Neuhuber, W.; Fischer, M. J.; Ott, C.; Linz, P.; Freisinger, W.; Heinlein, S.; Schmidt, S. T.; Schmieder, R. E.; Amann, K.; Scrogin, K. E.; Veelken, R.; Ditting, T.
Article Title: Complex Re-Innervation Pattern After Unilateral Renal Denervation in Rats
Abstract: Renal denervation (DNX) is a treatment for resistant arterial hypertension. Efferent sympathetic nerves regrow, but re-innervation 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), calcitonin gene related peptide (CGRP) and smooth muscle actin were identified in kidney sections from 12 Sprague-Dawley rats, to distinguish afferents, efferents, and vasculature. DNX-kidneys and non-denervated kidneys were examined 1, 4 and 12 weeks after DNX. Tissue levels of CGRP and norepinephrine (NE) were measured with ELISA and mass-spectrometry, respectively. DNX decreased TH- and CGRP-label by 90% and 95%, respectively (P0.05) within one week. After 12 weeks TH- and CGRP-label returned to baseline with a shift towards afferent innervation (P0.05). Non-denervated kidneys showed a doubling of both labels within 12 weeks (P0.05). CGRP content decreased by 72% [3.2+/-0.3 vs. 0.9+/-0.2 ng/gkidney; P0.05] and NA by 78% [1.1+/-0.1 vs. 0.2+/-0.1 pmol/mgkidney; P0.05] one week after DNX. After 12 weeks, CGRP, but not NE content in DNX kidneys was fully recovered, with no changes in the non-denervated kidneys. The use of phenol in the DNX procedure did not influence this result. We found morphological re-innervation and transmitter recovery of afferents within 12 weeks 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 maybe contributing to the blood pressure lowering effect of DNX.
Journal Title: American journal of physiology.Regulatory, integrative and comparative physiology
ISSN: 1522-1490; 0363-6119
Publisher: American Journal of Physiology - Regulatory, Integrative and Comparative Physiology  
Date Published: 2016
Start Page: ajpregu.00227.2014
Language: ENG
Notes: LR: 20160226; CI: Copyright (c) 2014; JID: 100901230; OTO: NOTNLM; aheadofprint; SO: Am J Physiol Regul Integr Comp Physiol. 2016 Feb 24:ajpregu.00227.2014. doi: 10.1152/ajpregu.00227.2014.