Effect Of Renal Artery Radiofrequency Ablation Sympathetic Denervation On Renal Arterial Endothelial Function Of Pigs

Objective:To investigate the effects of radiofrequency ablation denervation at renal arteries on renal arterial endothelial function of pigs,and to evaluate the safety of procedures.Methods:A total of 15 male minipigs weighing approximately 20 kg were randomly divided into three groups:(1)control group(n=5),(2)sham-operation group(n=5),(3)renal denervation(RDN)group(n=5).The control group was not treated,and the sham-operation group performed other procedures except radiofrequency ablation,and the RDN group underwent bilateral reanl artery radiofrequency ablation procedures.After all pigs were fed a high-fat diet for 6 months,the effects of RDN on renal arterial histology,endothelial function and inflammation were studied.ResultsThe measurements of body weight after 6 months showed no significant statistical difference(p>0.05)between the RDN group(66.96±1.56 kg)and the sham operation group(67.80±1.36 kg).Hematoxylin and eosin(HE)staining results showed that compared to sham-operated group,the intima of RDN group was significantly thicker.Immunohistochemistry showed that the staining intensity of endothelin A receptor(ET_AR)and endothelin B receptor(ET_BR)in vascular smooth muscle cells were significantly increased and the relative proportion of ET_BR was significantly improved compared to sham-operated group.Western blot analysis showed that the phosphorylation expression levels of AMPK/Akt/eNOS protein pathway(0.30±0.11,0.35±0.08,0.35±0.08)and the production level of NO(1.86±0.62)in renal artery of RDN group were significantly lower than those(0.45±0.10,0.64±0.19,0.56±0.15,3.13±0.32)in the sham operation group(all p<0.05);and the relative expression levels of endothelin-1(ET-1),endothelin convertingenzyme1(ECE1),ET_ARandET_BRprotein(0.91±0.33,0.61±0.14,0.40±0.11,0.46±0.06)in RDN group were significantly higher than those(0.42±0.16,0.28±0.25,0.17±0.04,0.34±0.07)in sham operation group(all p<0.05);and the relative expression levels of NADPH oxidase catalyzed subunit NOX2 and 4-HNE,a lipid peroxidation product of polyunsaturated fatty acids(0.26±0.05,2.28±0.58)in RDN group,were significantly higher than those(0.12±0.06,1.51±0.33)of sham operation group(all p<0.05);and the reltive expression levels of cytoplasmic p-IκB and nuclear p-NF-κB p65 protein(0.38±0.13,0.14±0.06)in RDN group were significantly higher than those(0.18±0.10,0.07±0.03)in sham operation group(all p<0.05).There was no significant difference between the control group and the sham-operation group(all p>0.05).ConclusionRDN causes renal artery endothelial dysfunction and thickening of the intima,and promotes inflammation and increases the risk of renal atherosclerosis.