scholarly journals Renal sensory and sympathetic nerves reinnervate the kidney in a similar time-dependent fashion after renal denervation in rats

2013 ◽  
Vol 304 (8) ◽  
pp. R675-R682 ◽  
Author(s):  
Jan Mulder ◽  
Tomas Hökfelt ◽  
Mark M. Knuepfer ◽  
Ulla C. Kopp
Keyword(s):  
Substance P ◽  
Optical Density ◽  
Renal Denervation ◽  
Time Course ◽  
Sympathetic Nerves ◽  
Sensory Nerves ◽  
Sensory Innervation ◽  
Multiple Time ◽  
Sensory Reinnervation ◽  
Renal Sympathetic

Efferent renal sympathetic nerves reinnervate the kidney after renal denervation in animals and humans. Therefore, the long-term reduction in arterial pressure following renal denervation in drug-resistant hypertensive patients has been attributed to lack of afferent renal sensory reinnervation. However, afferent sensory reinnervation of any organ, including the kidney, is an understudied question. Therefore, we analyzed the time course of sympathetic and sensory reinnervation at multiple time points (1, 4, and 5 days and 1, 2, 3, 4, 6, 9, and 12 wk) after renal denervation in normal Sprague-Dawley rats. Sympathetic and sensory innervation in the innervated and contralateral denervated kidney was determined as optical density (ImageJ) of the sympathetic and sensory nerves identified by immunohistochemistry using antibodies against markers for sympathetic nerves [neuropeptide Y (NPY) and tyrosine hydroxylase (TH)] and sensory nerves [substance P and calcitonin gene-related peptide (CGRP)]. In denervated kidneys, the optical density of NPY-immunoreactive (ir) fibers in the renal cortex and substance P-ir fibers in the pelvic wall was 6, 39, and 100% and 8, 47, and 100%, respectively, of that in the contralateral innervated kidney at 4 days, 4 wk, and 12 wk after denervation. Linear regression analysis of the optical density of the ratio of the denervated/innervated kidney versus time yielded similar intercept and slope values for NPY-ir, TH-ir, substance P-ir, and CGRP-ir fibers (all R2 > 0.76). In conclusion, in normotensive rats, reinnervation of the renal sensory nerves occurs over the same time course as reinnervation of the renal sympathetic nerves, both being complete at 9 to 12 wk following renal denervation.

Abstract 476: Renal Sensory Reinnervation Following Acute Renal Denervation.

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Ulla Kopp ◽  
Jan Mulder ◽  
Tomas Hölt ◽  
Mark M Knuepfer
Keyword(s):  
Substance P ◽  
Optical Density ◽  
Renal Denervation ◽  
Blood Pressure Reduction ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Sensory Innervation ◽  
Multiple Time ◽  
Pelvic Wall ◽  
Sensory Reinnervation

It is known that efferent sympathetic nerves reinnervate the kidney following renal denervation (DNX). As there is evidence for lack of cardiac sensory reinnervation following heart transplantation, it has been thought that renal sensory nerves do not reinnervate following renal DNX. This absence of renal sensory reinnervation has been suggested to contribute to the chronic blood pressure reduction (3 years) in humans following renal DNX. However, whether renal sensory reinnervation occurs following acute renal DNX has not been thoroughly examined. Therefore, we assessed renal sensory innervation at multiple time points from 4 days to 12 wks following unilateral surgical DNX + application of phenol to the renal artery in normal Sprague Dawley rats. The contralateral innervated (INN) kidney served as control. Sensory innervation was determined as optical density (ImageJ) of the sensory nerves identified by immunohistochemistry using antibodies against the neuropeptides substance P and calcitonin-gene-related peptide (CGRP) in the renal pelvic wall, as it is a major site of renal sensory innervation. In INN kidneys, optical density of the sensory nerve fibers in the renal pelvic wall was unchanged over the 4 days - 12 wk period (n=17). In DNX kidneys, optical density of the substance P/CGRP containing sensory nerves was 3%, 30%, 50 % and 100% of the control contralateral INN kidney at 4 days, 2 wks, 4 wks and 12 wks, respectively, after DNX. Linear regression of optical density (DNX/INN) versus time yielded similar intercept and slope values for the substance P and CGRP containing sensory nerves (R 2 = 0.82 and 0.77, respectively, P<0.001 for both). Conclusion: in normal rats, sensory reinnervation of the renal pelvic wall is complete at 12 wks following acute surgical renal DNX.

Renal denervation alters cardiovascular and endocrine responses to hemorrhage in conscious newborn lambs

1998 ◽  
Vol 275 (1) ◽  
pp. H285-H291 ◽  
Author(s):  
Francine G. Smith ◽  
Isam Abu-Amarah
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Renal Denervation ◽  
Plasma Renin ◽  
Sympathetic Nerves ◽  
Renal Nerves ◽  
Elevated Plasma ◽  
Baseline Levels ◽  
Renal Sympathetic

To investigate the role of renal sympathetic nerves in modulating cardiovascular and endocrine responses to hemorrhage early in life, we carried out three experiments in conscious, chronically instrumented lambs with intact renal nerves (intact; n = 8) and with bilateral renal denervation (denervated; n = 5). Measurements were made 1 h before and 1 h after 0, 10, and 20% hemorrhage. Blood pressure decreased transiently after 20% hemorrhage in intact lambs and returned to control levels. In denervated lambs, however, blood pressure remained decreased after 60 min. After 20% hemorrhage, heart rate increased from 170 ± 16 to 207 ± 18 beats/min in intact lambs but not in denervated lambs, in which basal heart rates were already elevated to 202 ± 21 beats/min. Despite an elevated plasma renin activity (PRA) measured in denervated (12.0 ± 6.4 ng ANG I ⋅ ml−1 ⋅ h−1) compared with intact lambs (4.0 ± 1.1 ng ANG I ⋅ ml−1 ⋅ h−1), the increase in PRA in response to 20% hemorrhage was similar in both groups. Plasma levels of arginine vasopressin increased from 11 ± 8 to 197 ± 246 pg/ml after 20% hemorrhage in intact lambs but remained unaltered in denervated lambs from baseline levels of 15 ± 10 pg/ml. These observations provide evidence that in the newborn, renal sympathetic nerves modulate cardiovascular and endocrine responses to hemorrhage.

scholarly journals Effects of Renal Denervation via Renal Artery Adventitial Cryoablation on Atrial Fibrillation and Cardiac Neural Remodeling

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Wei Wang ◽  
Zhaolei Jiang ◽  
Rongxin Lu ◽  
Hao Liu ◽  
Nan Ma ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Renal Artery ◽  
Renal Denervation ◽  
Sham Group ◽  
Stellate Ganglion ◽  
Sympathetic Nerves ◽  
Postoperative Recovery ◽  
Therapeutic Approaches ◽  
Neural Remodeling ◽  
Renal Sympathetic

Introduction. Catheter-based renal denervation (RDN) could reduce cardiac sympathetic nerve activity (SNA) and inhibit atrial fibrillation (AF). However, the reliability is uncertain, because the renal sympathetic nerves are mainly distributed in the adventitial surface of the renal artery. Objective. The aims of this study were to test the hypothesis that renal artery adventitial ablation (RAAA) definitely had the effects of RDN and to study the effects of RDN via renal artery adventitial cryoablation (RAAC) on AF and cardiac neural remodeling. Methods. Twenty beagle canines were randomly assigned to two groups: the left RDN group (LRDN, n=10), which underwent left RDN via RAAC; the Sham group (n=10). After 2 months of postoperative recovery, AF vulnerability, AF duration, and histological examination were performed in both groups. Results. Compared with the Sham group, left stellate ganglion (LSG) tissue fibrosis was increased in the LRDN group. LRDN significantly increased the percentage of TH-negative ganglionic cells and decreased the density of TH-positive nerves in the LSG (P<0.001). Also, the densities of TH-positive nerves and GAP43 immunoreactivity within the left atrium (LA) were significantly decreased in the LRDN group (P<0.05). After LA burst pacing, all 10 canines (100%) could be induced AF in the Sham group, but only 4 of 10 canines (40%) could be induced AF in the LRDN group (P=0.011). The percentage of LA burst stimulation with induced AF was 26.7% (8/30) in the LRDN group, which was significantly decreased compared with that of the Sham group (53.3%, 16/30) (P=0.035). In addition, AF duration was also significantly decreased in the LRDN group (13.3 ± 5.1 s) compared with that of the Sham group (20.3 ± 7.3 s, P=0.024). Conclusions. RDN via RAAC could cause cardiac neural remodeling and effectively inhibit AF inducibility and shorten AF duration. It may be useful in selecting therapeutic approaches for AF patients.

Role of renal sympathetic nerves in response of the ovine fetus to volume expansion

1990 ◽  
Vol 259 (5) ◽  
pp. R1050-R1055 ◽  
Author(s):  
F. G. Smith ◽  
T. Sato ◽  
O. J. McWeeny ◽  
J. M. Klinkefus ◽  
J. E. Robillard
Keyword(s):  
Volume Expansion ◽  
Renal Denervation ◽  
Sympathetic Nerves ◽  
Renal Hemodynamics ◽  
Fetal Life ◽  
Renal Nerve ◽  
Fetal Sheep ◽  
Arterial Blood ◽  
Renal Sympathetic

To investigate the role of renal sympathetic nerves in the fetal response to hypervolemia, studies were carried out in conscious, chronically instrumented fetal sheep aged 137-142 days of gestation. Bilateral renal denervation (n = 9) or sham surgery (n = 8) was carried out under halothane anesthesia 3-6 days before experiments. Bilateral renal denervation did not alter basal fetal renal hemodynamics, glomerular filtration rate (GFR), or Na+ excretion. Volume expansion with 6% Dextran 70 (18 ml/kg) was associated with a fall in fetal hematocrit, a sustained increase in mean arterial blood pressure, and a sustained diuresis and natriuresis. There was no significant change in GFR during fetal hypervolemia from control levels of 4.51 +/- 0.74 ml/min (intact) and 4.43 +/- 0.43 ml/min (denervated). Atrial natriuretic factor increased from 144 +/- 34 to 464 +/- 134 pg/ml, and plasma renin activity decreased from 5.15 +/- 1.7 to 3.04 +/- 1.0 ng.ml-1.h-1 in intact animals, within 30 min of completion of the dextran infusion. Similar changes occurred in denervated fetuses. Plasma aldosterone levels remained constant in intact and denervated fetuses during hypervolemia at control levels of 40.8 +/- 5.4 and 59.3 +/- 8.4 pg/ml, respectively. These findings suggest that renal sympathetic nerves do not influence basal renal hemodynamics or function and do not appear to play an important role in the natriuretic response to volume expansion during fetal life. This can be explained by a low tonic renal nerve activity before birth.

Plasma extravasation induced in rat trachea by 6-OHDA is mediated by sensory nerves, not by sympathetic nerves

1994 ◽  
Vol 76 (2) ◽  
pp. 701-707 ◽  
Author(s):  
I. Sulakvelidze ◽  
P. Baluk ◽  
D. M. McDonald
Keyword(s):  
Tyrosine Hydroxylase ◽  
Substance P ◽  
Knee Joint ◽  
Vascular Permeability ◽  
Sympathetic Nerves ◽  
Sensory Nerves ◽  
Plasma Extravasation ◽  
Chemical Sympathectomy ◽  
6 Hydroxydopamine ◽  
Rat Trachea

6-Hydroxydopamine (6-OHDA) stimulates the release of catecholamines from sympathetic nerves. This stimulation has been proposed as the basis of the 6-OHDA-induced increase in vascular permeability in the rat knee joint. We sought to determine whether 6-OHDA increases vascular permeability in the rat trachea through a similar mechanism. We also sought to determine whether sympathetic nerves contribute to the plasma extravasation caused by stimulating sensory nerves with capsaicin. In anesthetized rats, an intratracheal infusion of 6-OHDA caused more Monastral blue extravasation than did an infusion of vehicle (area density, 23 +/- 3% vs. 9 +/- 1%). Chemical sympathectomy, which reduced the number of tyrosine hydroxylase-immunoreactive nerves by 98%, did not reduce the amount of extravasation induced by 6-OHDA. However, pretreatment with capsaicin, which reduced the number of substance P-immunoreactive nerves by 95%, reduced the Monastral blue extravasation induced by 6-OHDA by 98%. Extravasation induced by stimulating sensory nerves with capsaicin was not significantly different in tracheae with or without sympathetic nerves. We conclude that in the rat trachea infusion of 6-OHDA causes plasma extravasation by stimulating sensory nerves, not by stimulating sympathetic nerves. Furthermore, sympathetic nerves are not essential for the plasma extravasation induced by capsaicin.

Renal nerves in compensatory renal response to contralateral renal denervation

1980 ◽  
Vol 238 (1) ◽  
pp. F26-F30 ◽  
Author(s):  
G. F. DiBona ◽  
L. L. Rios
Keyword(s):  
Sodium Excretion ◽  
Renal Denervation ◽  
Left Kidney ◽  
Fractional Excretion ◽  
Sympathetic Nerves ◽  
Renal Nerves ◽  
Renal Response ◽  
Fractional Sodium Excretion ◽  
Fractional Excretion Of Sodium ◽  
Renal Sympathetic

Acute unilateral renal denervation and the resultant antidiuresis and antinatriuresis are accompanied by a compensatory antidiuresis and antinatriuresis from the opposite kidney. The present study tested the hypothesis that the renal sympathetic nerves mediated this adaptive response. In the volume-expanded rat, acute left renal denervation increased left kidney fractional sodium excretion from 4.4 +/- 0.6 to 5.9 +/- 0.6%, while right kidney fractional sodium excretion decreased from 4.3 +/- 0.6 to 3.5 +/- 0.5%. Subsequent acute right renal denervation increased right kidney fractional sodium excretion from 3.5 +/- 0.5 to 4.7 +/- 0.6%. Measurement of efferent left renal sympathetic nerve activity before and after acute right renal denervation showed an increase from 10.9 +/- 0.8 to 16.0 +/- 1.4 Hz. When both kidneys were simultaneously subjected to acute renal denervation, fractional excretion of sodium increased bilaterally. In uninephrectomized rats subjected to acute denervation of the remaining kidney, fractional excretion of sodium increased. Glomerular filtration rate was unchanged throughout in all studies. These results demonstrate that the compensatory renal response to acute contralateral renal denervation is mediated by the efferent renal sympathetic nerves.

Sympathetic but not sensory denervation stimulates white adipocyte proliferation

2006 ◽  
Vol 291 (6) ◽  
pp. R1630-R1637 ◽  
Author(s):  
Michelle T. Foster ◽  
Timothy J. Bartness
Keyword(s):  
Sensory Nerve ◽  
Sympathetic Nerves ◽  
Cell Number ◽  
Sensory Nerves ◽  
Sensory Innervation ◽  
Fat Cell ◽  
Protein Marker ◽  
White Adipocyte ◽  
Sensory Denervation

White adipocyte proliferation is a hallmark of obesity, but it largely remains a mechanistic mystery. We and others previously demonstrated that surgical denervation of white adipose tissue (WAT) triggers increases in fat cell number, but it is unknown whether this was due to preadipocyte proliferation or maturation of existing preadipocytes that allowed them to be counted. In addition, surgical denervation severs not only sympathetic but also sensory innervation of WAT. Therefore, we tested whether sympathetic WAT denervation triggers adipocyte proliferation using 5-bromo-2′-deoxyuridine (BrdU) as a marker of proliferation and quantified BrdU-immunoreactive (ir) cells that were colabeled with AD-3-ir, an adipocyte-specific membrane protein marker. The unilateral denervation model was used for all experiments where Siberian hamster inguinal WAT (IWAT) was unilaterally denervated, the contralateral pad was sham denervated serving as a within-animal control, and then BrdU was injected systemically for 6 days. When IWAT was surgically denervated, severing both sympathetic and sensory nerves, tyrosine hydroxylase (TH)-ir, a sympathetic nerve marker, and calcitonin gene-related peptide (CGRP)-ir, a sensory nerve marker, were significantly decreased, and BrdU+AD-3-ir adipocytes were increased ∼300%. When IWAT was selectively sensory denervated via local microinjections of capsaicin, a sensory nerve-specific toxin, CGRP-ir, but not TH-ir, was decreased, and BrdU+AD-3-ir adipocytes were unchanged. When IWAT was selectively sympathetically denervated via local microinjections of 6-hydroxy-dopamine, a catecholaminergic-specific toxin, TH-ir, but not CGRP-ir, was significantly decreased, and BrdU+AD-3-ir adipocytes were increased ∼400%. Collectively, these data provide the first direct evidence that sympathetic nerves inhibit white adipocyte proliferation in vivo.

scholarly journals Quantification of Renal Sympathetic Vasomotion as a Novel End Point for Renal Denervation

Hypertension ◽  
2020 ◽  
Vol 76 (4) ◽  
pp. 1247-1255
Author(s):  
Peter Ricci Pellegrino ◽  
Irving H. Zucker ◽  
Yiannis S. Chatzizisis ◽  
Han-Jun Wang ◽  
Alicia M. Schiller
Keyword(s):  
Renal Denervation ◽  
Sympathetic Nerves ◽  
Intrathecal Administration ◽  
Renal Sympathetic Denervation ◽  
Interventional Treatment ◽  
Vascular Control ◽  
Renal Vasculature ◽  
Windkessel Model ◽  
Renal Vascular ◽  
Renal Sympathetic

Renal sympathetic denervation, a potentially revolutionary interventional treatment for hypertension, faces an existential problem due to the inability to confirm successful ablation of the targeted renal sympathetic nerves. Based on the observation that renal sympathetic nerve activity exerts rhythmic, baroreflex-driven, and vasoconstrictive control of the renal vasculature, we developed a novel technique for identifying rhythmic sympathetic vascular control using a time-varying, 2-component Windkessel model of the renal circulation. This technology was tested in 2 different animal models of renal denervation; 10 rabbits underwent chronic, surgical renal denervation, and 9 pigs underwent acute, functional renal denervation via intrathecal administration of ropivacaine. Both methods of renal denervation reduced negative admittance gain, negative phase shift renal vascular control at known sympathetic vasomotor frequencies, consistent with a reduction in vasoconstrictive, baroreflex-driven renal sympathetic vasomotion. Classic measures like mean renal blood flow and mean renal vascular resistance were not significantly affected in either model of renal denervation. Renal sympathetic vasomotion monitoring could provide intraprocedural feedback for interventionists performing renal denervation and serve more broadly as a platform technology for the evaluation and treatment of diseases affecting the sympathetic nervous system.

Effects of renal denervation on cardiovascular response to furosemide in conscious lambs

1995 ◽  
Vol 269 (1) ◽  
pp. H149-H152 ◽  
Author(s):  
F. G. Smith ◽  
A. M. Strack
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Arterial Pressure ◽  
Renal Denervation ◽  
Cardiovascular Response ◽  
Blood Pressure Response ◽  
Sympathetic Nerves ◽  
Renal Nerves ◽  
Before And After ◽  
Renal Sympathetic

The cardiovascular response to furosemide in the newborn and the role of renal sympathetic nerves in influencing this response have not been investigated. We hypothesized that in conscious lambs, furosemide would decrease blood pressure, the response being accentuated in the absence of renal sympathetic nerves. Pulsatile pressures and heart rates were measured before and after furosemide (2 mg/kg) administration to chronically instrumented lambs with either bilateral renal denervation (denervated, n = 8) or renal nerves intact (intact, n = 6). In intact lambs, mean arterial pressure remained constant after furosemide; in denervated lambs there was an increase in arterial pressure 20 min after furosemide (P < 0.001), and control levels were reached by 100 min. Basal heart rate was higher in denervated than in intact lambs (P = 0.009). In both groups of lambs, heart rate increased 40 min after furosemide and remained elevated. These data provide new information that, in conscious newborn animals, renal sympathetic nerves influence the blood pressure response to furosemide, as well as basal control of heart rate.

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