Wen Zhao

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. This study aims to evaluate the risk of atherosclerosis induced by RDN in renal arteries. A 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). The 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 (ET_BR) 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 (ET_AR) and ET_BR; 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). RDN aggravated endothelial endocrine dysfunction and intimal thickening, and increased the risk of atherosclerosis in renal arteries of HFD-fed pigs.

Resistant hypertension and renal sympathetic hyperactivity are closely linked, and catheter-based renal denervation (RDN) is regarded as a new treatment strategy. However, the acute changes in vascular morphology and relaxation function have yet to be evaluated, and these may be important for the efficacy and safety of the procedure. In this study, we explored these questions by conventional temperature-controlled cardiac radiofrequency catheter-based RDN in a pig model. Six mini-pigs were randomly divided into the renal denervation (RDN) group (n = 3) and the Sham-RDN group (n = 3). Animals in the RDN group underwent unilateral radiofrequency ablation, and those in the Sham-RDN group underwent the same procedure except for the ablation. The pigs were examined by angiography pre- and post-RDN and were euthanized immediately thereafter. Renal arteries were processed for histological and molecular biology analyses as well as for in vitro vascular tension testing. Compared with the Sham-RDN group, the RDN caused vascular intima and media injury, renal nerve vacuolization, mild collagen fiber hyperplasia and elastic fiber cleavage (all p < 0.05). The RDN group also significantly exhibited nitric oxide synthase pathway inhibition and decreased endothelium-independent vascular relaxation function Compared to the Sham-RDN group (all p < 0.05). In this porcine model, renal artery denervation led to vascular wall injury and endothelial dysfunction in the acute phase, which negatively affected vascular relaxation function. Thus, this process may be detrimental to the prognosis and progress of hypertension patients.