Effects and Mechanisms of Radiofrequency Ablation of Renal Sympathetic Nerve on Anti-Hypertension in Canine

Abstract

BackgroundRadiofrequency ablation of renal sympathetic nerve (RDN) shows effective BP reduction in hypertensive patients while the specific mechanisms remain unclear.ObjectiveWe hypothesized that abnormal levels of norepinephrine (NE) and changes in NE-related enzymes and angiotensinconverting enzyme 2 (ACE2), angiotensin (Ang)-(1-7) and Mas receptor mediate the anti-hypertensive effects of RDN.MethodsMean values of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were assessed at baseline and follow-up. Plasma and renal norepinephrine (NE) concentrations were determined using highperformance liquid chromatography with electrochemical detection, and levels of NE-related enzyme and ACE2-Ang(1-7)- Mas were measured using real time PCR, Western blot and immunohistochemistry or Elisa in a hypertensive canine model fed with high-fat diet and treated with RDN. The parameters were also determined in a sham group treated with renal arteriography and a control group fed with normal diet.ResultsRDN decreased SBP, DBP, MAP, plasma and renal NE. Compared with the sham group, renal tyrosine hydroxylase (TH) expression was lower and renalase expression was higher in the RDN group. Compared with the control group, renal TH and catechol-o-methyl transferase (COMT) were higher and renalase was lower in the sham group. Moreover, renal ACE2, Ang-(1-7) and Mas levels of the RDN group were higher than those of the sham group, which were lower than those of the control group.ConclusionRDN shows anti-hypertensive effect with reduced NE and activation of ACE2-Ang(1-7)-Mas, indicating that it may contribute to the anti-hypertensive effect of RDN.

Patient‐Specific Factors Predicting Renal Denervation Response in Patients With Hypertension: A Systematic Review and Meta‐Analysis

“…Renal sympathetic overactivity and the renal plexus is an important component of the development of hypertension. 68 , 69 Sensory (afferent) renal nerves mainly sense the incoming information including volume changes and pressure changes, while and efferent renal nerves respond to the incoming information from afferent renal nerves, resulting in salt and water retention and activation of the RAAS, 68 , 70 , 71 , 72 which finally leads to an increase in systemic BP. Therefore, patients with hypertension characterized by sympathetic nervous system or RAAS overactivity are often considered sensitive to RDN.…”

Effects of different ablation points of renal denervation on the efficacy of resistant hypertension

“…Therefore, there is an urgent need of searching for alternative ways to effectively treat hypertension, particularly resistant hypertension ( Verloop, Voskuil & Doevendans, 2013 ; Azizi et al, 2015 ; deJong et al, 2016 ). Recent evidence indicated that hyperactivation of the renal sympathetic nerves could lead to decreased water and sodium reabsorption as well as renal blood flow and stimulate the renin-angiotensin-aldosterone system, leading to elevated BP ( Henegar et al, 2015 ; Fengler et al, 2017 ; Chen et al, 2017 ). During the past decade, a number of studies have extensively evaluated the regulation of BP by reducing renal sympathetic activity through invasive and noninvasive treatments ( Fengler et al, 2016 ; Mahfoud et al, 2017 ).…”