Blunted diuretic and natriuretic responses to acute sodium loading early after catheter-based renal denervation in normotensive sheep

Zoe McArdle, Roberto B. Pontes, Song T. Yao, Yugeesh R. Lankadeva, Reetu R. Singh, Sally G. Hood, Markus P. Schlaich, Clive N. May, Lindsea C. Booth

Research output: Contribution to journalArticle

Abstract

Catheter-based renal denervation (RDN) was introduced as a treatment for resistant hyperten-sion. There remain critical questions regarding the physiological mechanisms underlying the hypotensive effects of catheter-based RDN. Previous studies indicate that surgical denervation reduces renin and the natriuretic response to saline loading; however, the effects on these variables of catheter-based RDN, which does not yield complete denervation, are largely unknown. The aim of this study was to investigate the effects of catheter-based RDN on glo-merular-associated renin and regulation of fluid and sodium homeo-stasis in response to physiological challenges. First, immunohisto-chemical staining for renin was performed in normotensive sheep (n = 6) and sheep at 1 wk (n = 6), 5.5 mo (n = 5), and 11 mo (n = 5) after unilateral RDN using the same catheter used in patients (Symplicity). Following catheter-based RDN (1 wk), renin-positive glomeruli were significantly reduced compared with sham animals (P < 0.005). This was sustained until 5.5 mo postdenervation. To determine whether the reduction in renin after 1 wk had physiological effects, in a separate cohort, Merino ewes were administered high and low saline loads before and 1 wk after bilateral RDN (n = 9) or sham procedure (n = 8). After RDN (1 wk), the diuretic response to a low saline load was significantly reduced (P < 0.05), and both the diuretic and natriuretic responses to a high saline load were significantly attenuated (P < 0.05). In conclusion, these findings indicate that catheter-based RDN acutely alters the ability of the kidney to regulate fluid and electrolyte balance. Further studies are required to determine the long-term effects of catheter-based RDN on renal sodium and water homeostasis.

Original languageEnglish
Pages (from-to)R319-R327
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume317
Issue number2
DOIs
Publication statusPublished - 1 Aug 2019

Fingerprint

Denervation
Diuretics
Sheep
Catheters
Sodium
Kidney
Renin
Water-Electrolyte Balance
Homeostasis
Staining and Labeling

Cite this

McArdle, Zoe ; Pontes, Roberto B. ; Yao, Song T. ; Lankadeva, Yugeesh R. ; Singh, Reetu R. ; Hood, Sally G. ; Schlaich, Markus P. ; May, Clive N. ; Booth, Lindsea C. / Blunted diuretic and natriuretic responses to acute sodium loading early after catheter-based renal denervation in normotensive sheep. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2019 ; Vol. 317, No. 2. pp. R319-R327.
@article{27799f7a156f482887ccab7fcdd63d7f,
title = "Blunted diuretic and natriuretic responses to acute sodium loading early after catheter-based renal denervation in normotensive sheep",
abstract = "Catheter-based renal denervation (RDN) was introduced as a treatment for resistant hyperten-sion. There remain critical questions regarding the physiological mechanisms underlying the hypotensive effects of catheter-based RDN. Previous studies indicate that surgical denervation reduces renin and the natriuretic response to saline loading; however, the effects on these variables of catheter-based RDN, which does not yield complete denervation, are largely unknown. The aim of this study was to investigate the effects of catheter-based RDN on glo-merular-associated renin and regulation of fluid and sodium homeo-stasis in response to physiological challenges. First, immunohisto-chemical staining for renin was performed in normotensive sheep (n = 6) and sheep at 1 wk (n = 6), 5.5 mo (n = 5), and 11 mo (n = 5) after unilateral RDN using the same catheter used in patients (Symplicity). Following catheter-based RDN (1 wk), renin-positive glomeruli were significantly reduced compared with sham animals (P < 0.005). This was sustained until 5.5 mo postdenervation. To determine whether the reduction in renin after 1 wk had physiological effects, in a separate cohort, Merino ewes were administered high and low saline loads before and 1 wk after bilateral RDN (n = 9) or sham procedure (n = 8). After RDN (1 wk), the diuretic response to a low saline load was significantly reduced (P < 0.05), and both the diuretic and natriuretic responses to a high saline load were significantly attenuated (P < 0.05). In conclusion, these findings indicate that catheter-based RDN acutely alters the ability of the kidney to regulate fluid and electrolyte balance. Further studies are required to determine the long-term effects of catheter-based RDN on renal sodium and water homeostasis.",
keywords = "Catheter-based renal denervation, Diuresis, Intrarenal renin, Natriure-sis, Renal nerves",
author = "Zoe McArdle and Pontes, {Roberto B.} and Yao, {Song T.} and Lankadeva, {Yugeesh R.} and Singh, {Reetu R.} and Hood, {Sally G.} and Schlaich, {Markus P.} and May, {Clive N.} and Booth, {Lindsea C.}",
year = "2019",
month = "8",
day = "1",
doi = "10.1152/ajpregu.00228.2018",
language = "English",
volume = "317",
pages = "R319--R327",
journal = "American Journal of Physiology - Regulatory Intergrative Compartive Physiology",
issn = "0363-6119",
publisher = "American Physiological Society",
number = "2",

}

Blunted diuretic and natriuretic responses to acute sodium loading early after catheter-based renal denervation in normotensive sheep. / McArdle, Zoe; Pontes, Roberto B.; Yao, Song T.; Lankadeva, Yugeesh R.; Singh, Reetu R.; Hood, Sally G.; Schlaich, Markus P.; May, Clive N.; Booth, Lindsea C.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 317, No. 2, 01.08.2019, p. R319-R327.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Blunted diuretic and natriuretic responses to acute sodium loading early after catheter-based renal denervation in normotensive sheep

AU - McArdle, Zoe

AU - Pontes, Roberto B.

AU - Yao, Song T.

AU - Lankadeva, Yugeesh R.

AU - Singh, Reetu R.

AU - Hood, Sally G.

AU - Schlaich, Markus P.

AU - May, Clive N.

AU - Booth, Lindsea C.

PY - 2019/8/1

Y1 - 2019/8/1

N2 - Catheter-based renal denervation (RDN) was introduced as a treatment for resistant hyperten-sion. There remain critical questions regarding the physiological mechanisms underlying the hypotensive effects of catheter-based RDN. Previous studies indicate that surgical denervation reduces renin and the natriuretic response to saline loading; however, the effects on these variables of catheter-based RDN, which does not yield complete denervation, are largely unknown. The aim of this study was to investigate the effects of catheter-based RDN on glo-merular-associated renin and regulation of fluid and sodium homeo-stasis in response to physiological challenges. First, immunohisto-chemical staining for renin was performed in normotensive sheep (n = 6) and sheep at 1 wk (n = 6), 5.5 mo (n = 5), and 11 mo (n = 5) after unilateral RDN using the same catheter used in patients (Symplicity). Following catheter-based RDN (1 wk), renin-positive glomeruli were significantly reduced compared with sham animals (P < 0.005). This was sustained until 5.5 mo postdenervation. To determine whether the reduction in renin after 1 wk had physiological effects, in a separate cohort, Merino ewes were administered high and low saline loads before and 1 wk after bilateral RDN (n = 9) or sham procedure (n = 8). After RDN (1 wk), the diuretic response to a low saline load was significantly reduced (P < 0.05), and both the diuretic and natriuretic responses to a high saline load were significantly attenuated (P < 0.05). In conclusion, these findings indicate that catheter-based RDN acutely alters the ability of the kidney to regulate fluid and electrolyte balance. Further studies are required to determine the long-term effects of catheter-based RDN on renal sodium and water homeostasis.

AB - Catheter-based renal denervation (RDN) was introduced as a treatment for resistant hyperten-sion. There remain critical questions regarding the physiological mechanisms underlying the hypotensive effects of catheter-based RDN. Previous studies indicate that surgical denervation reduces renin and the natriuretic response to saline loading; however, the effects on these variables of catheter-based RDN, which does not yield complete denervation, are largely unknown. The aim of this study was to investigate the effects of catheter-based RDN on glo-merular-associated renin and regulation of fluid and sodium homeo-stasis in response to physiological challenges. First, immunohisto-chemical staining for renin was performed in normotensive sheep (n = 6) and sheep at 1 wk (n = 6), 5.5 mo (n = 5), and 11 mo (n = 5) after unilateral RDN using the same catheter used in patients (Symplicity). Following catheter-based RDN (1 wk), renin-positive glomeruli were significantly reduced compared with sham animals (P < 0.005). This was sustained until 5.5 mo postdenervation. To determine whether the reduction in renin after 1 wk had physiological effects, in a separate cohort, Merino ewes were administered high and low saline loads before and 1 wk after bilateral RDN (n = 9) or sham procedure (n = 8). After RDN (1 wk), the diuretic response to a low saline load was significantly reduced (P < 0.05), and both the diuretic and natriuretic responses to a high saline load were significantly attenuated (P < 0.05). In conclusion, these findings indicate that catheter-based RDN acutely alters the ability of the kidney to regulate fluid and electrolyte balance. Further studies are required to determine the long-term effects of catheter-based RDN on renal sodium and water homeostasis.

KW - Catheter-based renal denervation

KW - Diuresis

KW - Intrarenal renin

KW - Natriure-sis

KW - Renal nerves

UR - http://www.scopus.com/inward/record.url?scp=85069881869&partnerID=8YFLogxK

U2 - 10.1152/ajpregu.00228.2018

DO - 10.1152/ajpregu.00228.2018

M3 - Article

VL - 317

SP - R319-R327

JO - American Journal of Physiology - Regulatory Intergrative Compartive Physiology

JF - American Journal of Physiology - Regulatory Intergrative Compartive Physiology

SN - 0363-6119

IS - 2

ER -