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

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2019-08, Vol.317 (2), p.R319-R327
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Ablation; Animals; Blood Pressure - drug effects; Blood Pressure - physiology; Catheters; Catheters - adverse effects; Denervation; Denervation - methods; Diuretics; Diuretics - pharmacology; Electrolyte balance; Homeostasis; Hypertension; Hypertension - physiopathology; Kidney - drug effects; Kidney - metabolism; Kidney - physiopathology; Kidneys; Long-term effects; Medical instruments; Physiological effects; Physiology; Renal Artery - physiopathology; Renin; Renin - metabolism; Sheep; Sodium; Sodium - metabolism
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00228.2018

Catheter-based renal denervation (RDN) was introduced as a treatment for resistant hypertension. 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 glomerular-associated renin and regulation of fluid and sodium homeostasis in response to physiological challenges. First, immunohistochemical staining for renin was performed in normotensive sheep ( = 6) and sheep at 1 wk ( = 6), 5.5 mo ( = 5), and 11 mo ( = 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 ( < 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 ( = 9) or sham procedure ( = 8). After RDN (1 wk), the diuretic response to a low saline load was significantly reduced ( < 0.05), and both the diuretic and natriuretic responses to a high saline load were significantly attenuated ( < 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.