Renal simplicity denervation reduces blood pressure and renal injuries in an obesity‐induced hypertension dog model

Abstract

This study aimed to investigate the effects of renal sympathetic denervation (RDN) on blood pressure, renal function, and renal tissue pathological changes in obesity-induced hypertensive dogs. Thirty-two beagle dogs (10-12 months) were randomized to the control (n=10) and model groups (n=22). High-fat diet (HFD) was used to establish the obesity-induced hypertensive model. After 3 months of HFD, 20 animals with successfully induced hypertension were randomized to the RDN (n=10) and sham groups (n=10). Renal artery angiography, body weight, blood pressure, heart rate (HR), and blood and urine biochemistry were determined 1, 3 and 6 months after surgery. Models were killed 6 months after surgery. Pathological changes in the renal artery and renal tissue were assessed. The HFD group had significantly (P<.05) increased body weight, HR, and blood pressure, and higher levels of urine albumin, serum noradrenaline, and angiotensin II compared with controls. After RDN, blood pressure was decreased compared with baseline and the sham group (P<.05). In the RDN group, examination of the renal artery and renal tissue showed intact intima of renal artery in the surgical area, renal sympathetic nerve degeneration, necrosis, and dissolution, and widened space between nerve fibres. Hypertension-induced renal pathological changes were mild to moderate in the RDN group, but severe in the sham group. The control group had normal glomerular structure. In conclusion, RDN can effectively lower blood pressure in obesity-induced hypertensive dogs, as well as hypertension-induced renal pathological changes.

Abdominal Aortic Calcifications Influences the Systemic and Renal Hemodynamic Response to Renal Denervation in the DENERHTN (Renal Denervation for Hypertension) Trial

“…This phenomenon is exacerbated in the presence of AAC and aortic stiffening, which induce the transmission of abnormally high pulsatile stresses in renal microvessels . In this pathophysiological context, the maintenance of eGFR despite a large decrease in BP suggests that the addition of RDN to SSAHT including a renin–angiotensin system blocker and a calcium channel blocker (acting on postglomerular and both pre‐and postglomerular resistances, respectively) may have induced specific and subtle renal hemodynamic changes detectable only in the patients with the lowest AAC burden, as expected from experimental models . A small cohort study reported an increase in renal artery mean flow 6 months after RDN, as assessed by 3‐dimensional magnetic resonance angiography .…”

“…25,26 In this pathophysiological context, the maintenance of eGFR despite a large decrease in BP suggests that the addition of RDN to SSAHT including a reninangiotensin system blocker and a calcium channel blocker (acting on postglomerular and both pre-and postglomerular resistances, 27 respectively) may have induced specific and subtle renal hemodynamic changes detectable only in the patients with the lowest AAC burden, as expected from experimental models. 28,29 A small cohort study reported an increase in renal artery mean flow 6 months after RDN, as assessed by 3-dimensional magnetic resonance angiography. 30 In addition, renal vascular resistance has been shown to decrease 3 to 6 months after RDN in patients with resistant hypertension, 31,32 with no significant increase in renal perfusion detectable on MRI 33 or improvement in renal oxygenation, as determined by blood oxygen level-dependent MRI.…”

Weight-gain induced changes in renal perfusion assessed by contrast-enhanced ultrasound precede increases in urinary protein excretion suggestive of glomerular and tubular injury and normalize after weight-loss in dogs

“…In the current study, absolute dietary fat intake increased with food intake in the weight-change group. However, the diet was the same for both groups and thus the macronutrient ratio remained the same and was not extreme compared to other studies [16][17][18]. Furthermore, increased cardiac output in obesity is more strongly correlated with fat-free body mass than with fat mass [46].…”

“…In the canine model of obesity-induced hypertension, 10% weight-gain increases heart rate, cardiac output, and blood pressure [44]. However, weight-gain is often induced by feeding a high amount of fat in canine models of obesity [16][17][18]. In fact, dogs already show increased heart rate on the first day of a diet supplemented with beef fat [45].…”

“…Plasma clearance of exo-iohexol was used as a gold standard for renal function. Although animal models demonstrate that obesity can cause kidney injury and dysfunction [15][16][17][18] and human studies show that weight-loss can improve kidney function [3,19,20], to our knowledge, no study has examined kidney function and injury during the development of obesity and after weight-loss in the same individual yet. Furthermore, using dogs, which have been previously used as models for the study of diet-induced obesity and the kidney [17,[21][22][23], allows for a highly controlled study that is otherwise difficult to perform with human subjects.…”