Effect Of Catheter-Based Renal Denervation On Glomerular Structure And Function In Hypertensive Canine

Objective:To observe the effect of catheter-based renal sympathetic denervation (RDN) on the blood pressure, renal function, Tumor Growth Factor β1(TGF-β1), Angiotensin II (Angll), Norepinephrine (NE) in high fat diet-induced hypertensive canines. Secondarily, we observed the effect of RDN on Glomerular Structure and Function, and discuss its possible mechanism in ameliorating glomerular lesions.Methods:(1) Twenty eight Beagles of age between10-12months were included in the study and were divided into control group (n=6) and model group (n=22). Hypertension model was established by feeding the animals with high-fat diet, but two beagle were not successful, data were excluded.(2) After12weeks of feeding, animals in the model group was randomly divided into RDN group (n=10) and sham group (n=10). RDN group underwent catheter-based radiofrequency renal denervation whereas animals in sham group underwent only the renal angiography. Renal angiography was re-performed at3months post-procedure.(3) Six months after the initial procedure, all animals were sacrificed. The kidney were quickly extirpated and subjected to HE, Masson, PAS, and PASM staining. The protein expression of Desmin and TGF-β1were examined with Western Blot. The mRNA expression of Desmin was evaluated with Real Time PCR. Renal NE and AngⅡ level were detected with High Performance Liquid Chromatography (HPLC) and ELISA respectively.Results:(1)After12weeks of high fat diet feeding, compared to baseline and control group, body weight, heart rate, systolic blood pressure (SBP), diastolic heart pressure (DBP), mean arterial pressure (MAP), urine protein, AngⅡ and NE increased significantly in the RDN group and sham group(P<0.05).(2) In RDN group,1,2,4, and6month post-operative SBP, DBP, and MAP were lower than pre (P<0.05). In RDN group,2,4, and6month post-operative SBP, DBP, and MAP were lower than sham group (P<0.05).(3)In RDN group,3and6month post-operative urine protein were lower than sham group (P<0.05) and higher than control group(P<0.05). The protein and mRNA expression of desmin as well as TGF-(31protein in RDN group were significantly lower than those of sham group (all P<0.05). TGF-β1protein in RDN group were significantly higher than those of control group(P<0.05).(4)The expression of NE and AngⅡ in RDN group were significantly lower than those of sham group and than pre (all P<0.05). In RDN group, The expression of renal NE and AngⅡ were lower than those of sham group (all P<0.05).(5)RDN group:Basal membrane cells and Mesangial matrix Mild-to-moderate increased Focal segmental glomerular sclerosis, Basement membrane thickening, foot process fusion, Glomerular and renal capsule adhesion. Sham group:Basal membrane cells and Mesangial matrix Severe increased, Diffuse sexual glomerular sclerosis and Focal segmental glomerular sclerosis, Basement membrane thickening, foot process fusion, Glomerular and renal capsule adhesion. The glomerular sclerosis rate and segmental sclerosis rate in RDN group were significantly lower than those of sham group (P<0.05).Conclusions:(1)RDN can effectively lower SBP、DBP、MAP in a short term in hypertensive canines.(2)RDN can lower urine protein、 delay glomeruli damage which caused by hypertension and reduce glomerular sclerosis.(3)RDN may decrease serum and renal AngⅡ and NE by decrease Sympathetic nerve activity and blood pressure to improve Hypertensive glomerular damage.