Renal Denervation Findings On Cardiac And Renal Fibrosis In Rats With Isoproterenol Induced Cardiomyopathy

Objective:Cardio-renal fibrosis plays key roles in heart failure and chronic kidney disease. We sought to determine the effects of renal denervation (RDN) on cardiac and renal fibrosis in rats with isoproterenol induced cardiomyopathy (IPiCMP).Methods:Sixty male Sprague Dawley rats were randomly assigned to Control (n= 10) and IPiCMP (n= 50). At week 5,31 survival IPiCMP rats were randomized to RDN (n= 15) and Sham group (n= 16). LVEF (left ventricular ejection fraction), IVSd (diastolic interventricular septal thickness) and LAD (left atrium dimension) were measured by echocardiogram at baseline,5 and 10 weeks. The rats of all three groups were sacrificed at 10 weeks and the cardio-renal tissue was separated for analysis. The level of fibrosis was detected by Masson staining, plasma BNP, NE, ALD, AngⅡ, Ang-(1-7), TNF-a, CRP, PINP, PIIINP and PICP concentration was measured by ELISA kit, the protein expression of ACE, ACE2, AT1R, Mas-R, TGF-β1, MMP2 and Collagen I was determined by Western blots.Results:Compared with Control group, EF was decreased, IVSd and LAD were increased in IPiCMP group at week 5. After 10 weeks, cardiorenal pathophysiologic results demonstrated that the collagen volume fraction of left atrio-ventricular and kidney tissues reduced significantly in RDN group compared with Sham group. Moreover the profibrosis factors (TGF-β1, MMP2 and Collagen I), inflammatory cytokines (CRP and TNF-a), and collagen synthesis biomarkers (PICP, PINP and PIIINP) concentration significantly decreased in RDN group. Compared with Sham group, RDN group showed that release of noradrenaline and aldosterone were reduced, ACE/Ang Ⅱ/AT1R axis was downregulated. Meanwhile, ACE2/Ang-(1-7)/ Mas-R axis was upregulated.Conclusion:RDN inhibits cardio-renal fibrogenesis through multiple pathways, including reducing SNS over-activity, rebalancing RAAS axis and decreasing TGF-β1 expression.