Renal Sympathetic Denervation Protects the Failing Heart Via Inhibition of Neprilysin Activity in the Kidney

摘要: 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 effects radiofrequency renal nerve denervation (RF-RDN) on pathobiology HF interaction between nerves natriuretic peptide (NP) metabolism. Methods Spontaneously hypertensive rats (SHR) normotensive Wistar-Kyoto (WKY) were subjected 45 min coronary artery ligation reperfusion for 12 weeks. At 4 weeks post-reperfusion, SHR WKY underwent either bilateral RF-RDN or sham-RDN. Results Following both strains, LV ejection fraction remained significantly above those levels respective sham-RDN rats, at end 12-week study, strains had reduced fibrosis improved vascular function. therapy reactivity endothelium-dependent and -independent vasodilators as well compliance setting severe HF. Improvements function accompanied by significant elevations circulating NP compared associated with Further investigation into cause increased demonstrated that inhibited neprilysin activity Likewise, chronic treatment beta1 antagonist bisoprolol circulation Conclusions identifies a novel endogenous pathway which participate degradation cardioprotective NP. Furthermore, removal influence kidney attenuates activity, augments levels, reduces improves