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

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1 Citation (Scopus)

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

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