Abstract
BackgroundRenal denervation (RDN) targeting the sympathetic nerves in the renal arterial adventitia as a treatment of resistant hypertension can cause endothelial injury and vascular wall injury. This study aims to evaluate the risk of atherosclerosis induced by RDN in renal arteries.MethodsA total of 15 minipigs were randomly assigned to 3 groups: (1) control group, (2) sham group, and (3) RDN group (n = 5 per group). All pigs were fed a high-fat diet (HFD) for 6 months after appropriate treatment. The degree of intimal thickening of renal artery and the conversion of endothelin 1 (ET-1) receptors were evaluated by histological staining. Western blot was used to assess the expression of nitric oxide (NO) synthesis signaling pathway, ET-1 and its receptors, NADPH oxidase 2 (NOX2) and 4-hydroxynonenal (4-HNE) proteins, and the activation of NF-kappa B (NF-κB).ResultsThe histological staining results suggested that compared to the sham treatment, RDN led to significant intimal thickening and significantly promoted the production of endothelin B receptor (ETBR) in vascular smooth muscle cells (VSMCs). Western blotting analysis indicated that RDN significantly suppressed the expression of AMPK/Akt/eNOS signaling pathway proteins, and decreased the production of NO, and increased the expression of endothelin system proteins including endothelin-1 (ET-1), endothelin converting enzyme 1 (ECE1), endothelin A receptor (ETAR) and ETBR; and upregulated the expression of NOX2 and 4-HNE proteins and enhanced the activation of NF-kappa B (NF-κB) when compared with the sham treatment (all p < 0.05). There were no significant differences between the control and sham groups (all p > 0.05).ConclusionsRDN aggravated endothelial endocrine dysfunction and intimal thickening, and increased the risk of atherosclerosis in renal arteries of HFD-fed pigs.
Highlights
Renal denervation (RDN) targeting the sympathetic nerves in the renal arterial adventitia as a treatment of resistant hypertension can cause endothelial injury and vascular wall injury
Resistant hypertension, exhibiting elevated office blood pressure (BP, ≥130/80 mmHg), is a kind of common and complicated disease in clinical practice and is difficult to achieve control in patients despite treated with 3 or more different anti-hypertensive agents at best doses together including a diuretic according to the American Heart Association hypertension guidelines, which leads to increasing incidence of many complications such as renal injury, stroke and heart failure [1,2,3]
Body weight and serum creatinine levels and lipid profiles at baseline and after 6 months Compared with the baseline, the significant increases of body weight and Total cholesterol (TC) and significant decrease of High density lipoprotein cholesterol (HDL-C) were observed in pigs of control group (p = 0.000, p = 0.013, and p = 0.006, respectively), sham group (p = 0.000, p = 0.029, and p = 0.001, respectively) and RDN group (p = 0.000, p = 0.029, and p = 0.025, respectively) after a 6-month high-fat diet (HFD)
Summary
Renal denervation (RDN) targeting the sympathetic nerves in the renal arterial adventitia as a treatment of resistant hypertension can cause endothelial injury and vascular wall injury. Some studies have been conducted in clinical and preclinical animal models to assess the safety of the procedure, yet some problems, such as a short observation period, limited research scope including renal function, imaging and morphology of renal artery, exist [4,5,6]. The effects of the RDN procedure on the renal artery still need further study because radiofrequency energy is delivered transmurally and can cause vascular wall injury, which may cause endothelial dysfunction and result in an imbalanced release of an increased level of the endothelium-derived relaxation factor nitric oxide (NO) and a decreased level of the endothelium-derived constriction factor endothelin-1 (ET-1), thereby increasing the risk of atherosclerosis [7]. The vascular injury method combined with the use of a high-fat diet (HFD) may accelerate atherosclerosis progression [10, 11]
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