Renal Denervation Modulates Cardiac Sympathetic Nerve Dysfunction In Rats With Isoproterenol Induced Heart Failure

Aims The aim of this study was to investigate the effects of renal denervation on cardiac sympathetic nerve distribution and norepinephrine (NE) reuptake in Isoproterenol-induced Chronic Heart Failure (IPiCHF) rats.Methods Forty male Sprague Dawley rats were randomly assigned to control (n=6) and IPiCHF group (n=34). After three weeks intraperitoneal injection with ISO 10mg/kg/d and two weeks observation,20 survival rats in IPiCHF group were randomly divided into RDN group (n=10) and SHAM group (n=10). RDN was conducted in RDN group and sham operation was conducted in SHAM group. Echocardiography was implemented at week 10 to evaluate cardiac function in three groups; Masson stain was used to assess the level of cardiac fibrosis. Tyrosine hydroxylase (TH)-immunohistochemistry and western blot (WB) were used to assess cardiac sympathetic remodeling.Results Cardiac dysfunction was observed in IPiCHF group, detected by echocardiography at week 5. Ejection fraction (RDN vs SHAM:62.00±2.14% vs 55.05±1.98%, P<0.01) was elevated, while left ventricle mass (RDN vs SHAM: 814.64±49.37 mg vs 981.47±67.07 mg, P<0.05) was decreased in RDN group, compared with SHAM at week 10. Collagen volume fraction was significantly reduced in RDN group (RDN vs SHAM:7.26±2.19% vs 14.81±2.84%, P<0.05), compared with the SHAM group. According to the result of immunohistochemistry, the expression of renal tissue TH was significantly lower in RDN group compared with SHAM (average optical density, RDN vs SHAM:545.31±116.43 vs 1563.90±1118.45, P<0.001). Ventricular expression of TH (average optical density,363.31±38.11 vs 196.67±41.57, P=0.014), nerve growth factor (NGF) and growth-associated protein 43 (GAP43) were increased significantly in RDN group than the SHAM group. There was an increased trend of cardiac expression of norepinephrine transporter in RDN group compared with the SHAM group.Conclusion RDN could not only improve cardiac dysfunction and structure remodeling, but also modulate cardiac sympathetic remodeling in rats with IPiCHF.