Abstract 19164: Renal Sympathetic Denervation Modulates Natriuretic Peptides by Inhibiting Neprilysin in the Failing Heart
Introduction: Sustained pathological sympathetic activation that accompanies heart failure (HF) contributes to the progression of myocardial injury and left ventricular (LV) dysfunction. Neprilysin (NEP) degrades natriuretic peptides (NP) and attenuates the beneficial effects of natriuretic peptide signaling. We utilized radiofrequency renal nerve denervation (RF-RDN) in a rodent model of hypertension and heart failure to investigate whether renal efferent activity regulates NEP activity and regulates NP levels and signaling.
Methods: Spontaneously hypertensive rats (SHR) 20 weeks of age were subjected to 45 min of Left Anterior Descending coronary artery ligation followed by 12 weeks of reperfusion (Rep). 4 weeks following Rep, rats underwent either surgical bilateral radiofrequency RF-RDN (n=9) or sham RF-RDN (n=8) procedure (Biosense Webster Stockert 70 RF generator). Every 2 weeks, transthoracic echocardiograms were performed using Vevo 2100 (Visualsonics) to assess LV function. At 12 weeks plasma brain natriuretic peptide-32 (BNP), atrial natriuretic peptide (ANP), and c-type natriuretic peptide (CNP) were quantified using ELISA technique. Renal NEP activity was measured using the substrate, DAGNPG, and quantified using fluorometric detection.
Results: RF-RDN significantly preserved LV ejection fraction (49.4 vs. 32.1%, p < 0.05) at 12 weeks compared to sham. 12-week heart weight/tibia length was also markedly reduced in the RF-RDN group (41.1 vs. 48.7 mg/mm, p < 0.05). Despite improved LV function and reduced cardiac enlargement, 12-week plasma BNP (188.84 vs. 83.3 ng/ml, p < 0.05), ANP (297.0 vs. 57.0 ng/ml, p < 0.05) and CNP (1.42 vs. 0.87 ng/ml, p < 0.05) levels were significantly elevated in the RF-RDN treated group compared to sham. RF-RDN inhibited renal NEP activity compared to sham (559.4 vs. 729.7 RFU/min/mg, p < 0.05).
Conclusions: We have identified a novel link between the sympathetic nervous system and endogenous regulation of cardioprotective NPs. Sympathetic inhibition by RF-RDN inhibits renal NEP activity resulting in increased levels of NP, thereby contributing to cardiac protection in heart failure.
Author Disclosures: D.J. Polhemus: None. R. Trivedi: None. J. Gao: None. A. Scarborough: None. J. Valentino: None. T. Goodchild: None. D. Kapusta: None. F. Smart: None. D.J. Lefer: None.
- © 2016 by American Heart Association, Inc.