Effect Of Catheter-Based Renal Sympathetic Denervation On Oxidative Stress And Endothelial Function In Hypertensive Dogs

Objective:To observe the effect of renal sympathetic denervation (RSD) on the blood pressure, serum AngII, NADPH oxidase, MDA, NO, eNOS in diet-induced hypertensive dogs model. Secondarily, we observed the effect of RSD on oxidative stress, endothelial function, and the possible antihypertensive mechanism in hypertensive dogs.Methods:1. Hypertension model was established by feeding beagle dogs with high-fat and high-fat high-salt diet. Sixteen Beagles (10-12months old) were divided into normal control group (normal diet, n=4) and model group (fed with high-fat diet, n=6and with high-fat high-salt, n=6).2. After12weeks of feeding, the blood pressures of dogs were stable. The model group was then divided into operation group (renal sympathetic denervation) and sham-operation group (renal angiography). Renal angiography was re-performed at the3rd month after surgery.3. Blood pressure and heart rate were measured using noninvasive sphygmomanometers while body weights were measured using electronic weigher. Blood specimens were obtained at baseline (pre-modelling), pre-operative (12weeks after modelling), and post-operative (1st week,1st month, and3rd month). Serum Ang II level were measured with radioimmunoassay method; NADPH with enzyme-linked immunosorbent assay method; MDA with TBA method; NO with nitrate reductase; and eNOS with colorimetric assay.Results:1. After12weeks of modeling, the SBP, DBP, MAP and body weight of the model group (high-fat group and high-fat-salt group), significantly increased,there were significant difference compared with the baseline and the control group(P<0.05); the levels of AngII,NADPH oxidase, MDA of model group (high-fat group and high-fat-salt group) increased significantly, serum NO and eNOS levels decreased significant-ly, which had a statistical difference compared to the baseline and the control group (P<0.05).2. The SBP, DBP, and MAP of operation group at each time point after renal sympathetic denervation, were significantly lower, which had statistically significant differences(P<0.05) compared with the preoperative. The SBP, DBP, and MAP of1st month,2nd month and3rd month after surgery all had statistically significant differences when compared with the control group (P<0.05).3. AngII levels of1st month and3rd month after surgery were significantly reduced which had a statistically significant difference compared with the control group(P <0.05).Serum NADPH oxidase, MDA levels at each time point after renal sympathetic denervation all decreased while serum NO and eNOS increased, which had statistically significant difference compared to the preoperative (P<0.05).These serological markers levels of1st month and3rd month had statistically significant differences compared with the control group (P<0.05).Conclusions:1.In the model of diet-induced hypertension, increased oxidative stress and endothelial dysfunction may be one of the mechanisms for the increased blood pressure.2. Renal sympathetic denervation can significantly lower SBP, DBP, and MAP in hypertention dogs.3.Renal sympathetic denervation can reduce serum NADPH oxidase, MDA content, increase eNOS, NO content, result in inhibiting oxidative stress, improving endothelial function.