David J Polhemus1, Rishi K Trivedi1, Juan Gao1, Zhen Li1, Amy L Scarborough2, Traci T Goodchild1, Kurt J Varner1, Huijing Xia3, Frank W Smart4, Daniel R Kapusta1, David J Lefer5. 1. Cardiovascular Center of Excellence, Louisiana State University (LSU) Health Sciences Center, New Orleans, Louisiana; Department of Pharmacology and Experimental Therapeutics, LSU Health Sciences Center, New Orleans, Louisiana. 2. Cardiovascular Center of Excellence, Louisiana State University (LSU) Health Sciences Center, New Orleans, Louisiana. 3. Department of Pharmacology and Experimental Therapeutics, LSU Health Sciences Center, New Orleans, Louisiana. 4. Cardiovascular Center of Excellence, Louisiana State University (LSU) Health Sciences Center, New Orleans, Louisiana; Department of Medicine, Division of Cardiology, LSU Health Sciences Center, New Orleans, Louisiana. 5. Cardiovascular Center of Excellence, Louisiana State University (LSU) Health Sciences Center, New Orleans, Louisiana; Department of Pharmacology and Experimental Therapeutics, LSU Health Sciences Center, New Orleans, Louisiana. Electronic address: dlefe1@lsuhsc.edu.
Abstract
BACKGROUND: Sustained sympathetic activation contributes to the progression of myocardial cell injury, cardiac fibrosis, and left ventricular (LV) dysfunction in heart failure (HF). OBJECTIVES: This study investigated the effects of radiofrequency renal nerve denervation (RF-RDN) on the pathobiology of HF and the interaction between the renal sympathetic nerves and natriuretic peptide (NP) metabolism. METHODS: Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were subjected to 45 min of coronary artery ligation and reperfusion for 12 weeks. At 4 weeks post-reperfusion, SHR and WKY underwent either bilateral RF-RDN or sham-RDN. RESULTS: Following RF-RDN in both strains, LV ejection fraction remained significantly above those levels in respective sham-RDN rats, and at the end of the 12-week study, rats in both strains had significantly reduced LV fibrosis and improved vascular function. RF-RDN therapy significantly improved vascular reactivity to endothelium-dependent and -independent vasodilators as well as vascular compliance in the setting of severe HF. Improvements in LV function were accompanied by significant elevations in circulating NP as compared to those associated with sham-RDN. Further investigation into the cause of increased circulating NP levels demonstrated that RF-RDN significantly inhibited renal neprilysin activity in SHR and WKY with HF. Likewise, chronic treatment with the beta1 antagonist bisoprolol inhibited renal neprilysin activity and increased circulation NP levels in WKY with HF. CONCLUSIONS: This study identifies a novel endogenous pathway by which the renal nerves participate in the degradation of cardioprotective NP. Furthermore, removal of the influence of the renal nerves on kidney function attenuates renal neprilysin activity, augments circulating NP levels, reduces myocardial fibrosis, and improves LV function in the setting of HF.
BACKGROUND: Sustained sympathetic activation contributes to the progression of myocardial cell injury, cardiac fibrosis, and left ventricular (LV) dysfunction in heart failure (HF). OBJECTIVES: This study investigated the effects of radiofrequency renal nerve denervation (RF-RDN) on the pathobiology of HF and the interaction between the renal sympathetic nerves and natriuretic peptide (NP) metabolism. METHODS: Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were subjected to 45 min of coronary artery ligation and reperfusion for 12 weeks. At 4 weeks post-reperfusion, SHR and WKY underwent either bilateral RF-RDN or sham-RDN. RESULTS: Following RF-RDN in both strains, LV ejection fraction remained significantly above those levels in respective sham-RDN rats, and at the end of the 12-week study, rats in both strains had significantly reduced LV fibrosis and improved vascular function. RF-RDN therapy significantly improved vascular reactivity to endothelium-dependent and -independent vasodilators as well as vascular compliance in the setting of severe HF. Improvements in LV function were accompanied by significant elevations in circulating NP as compared to those associated with sham-RDN. Further investigation into the cause of increased circulating NP levels demonstrated that RF-RDN significantly inhibited renal neprilysin activity in SHR and WKY with HF. Likewise, chronic treatment with the beta1 antagonist bisoprolol inhibited renal neprilysin activity and increased circulation NP levels in WKY with HF. CONCLUSIONS: This study identifies a novel endogenous pathway by which the renal nerves participate in the degradation of cardioprotective NP. Furthermore, removal of the influence of the renal nerves on kidney function attenuates renal neprilysin activity, augments circulating NP levels, reduces myocardial fibrosis, and improves LV function in the setting of HF.
Authors: David J Polhemus; Rishi K Trivedi; Thomas E Sharp; Zhen Li; Traci T Goodchild; Amy Scarborough; Geoffrey de Couto; Eduardo Marbán; David J Lefer Journal: Basic Res Cardiol Date: 2019-01-17 Impact factor: 17.165
Authors: Kenichi Katsurada; Shyam S Nandi; Neeru M Sharma; Hong Zheng; Xuefei Liu; Kaushik P Patel Journal: Am J Physiol Renal Physiol Date: 2019-08-07
Authors: Simina-Ramona Selejan; Dominik Linz; Muriel Mauz; Mathias Hohl; Anh Khoa Dennis Huynh; Thimoteus Speer; Jan Wintrich; Andrey Kazakov; Christian Werner; Felix Mahfoud; Michael Böhm Journal: Basic Res Cardiol Date: 2022-07-14 Impact factor: 12.416
Authors: Derek J Hausenloy; Hans Erik Bøtker; Peter Ferdinandy; Gerd Heusch; G André Ng; Andrew Redington; David Garcia-Dorado Journal: Cardiovasc Res Date: 2019-06-01 Impact factor: 10.787