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.
Cardiovascular Center of Excellence, Louisiana State University (LSU) Health Sciences Center, New Orleans, Louisiana.
J Am Coll Cardiol. 2017 Oct 24;70(17):2139-2153. doi: 10.1016/j.jacc.2017.08.056.
Sustained sympathetic activation contributes to the progression of myocardial cell injury, cardiac fibrosis, and left ventricular (LV) dysfunction in heart failure (HF).
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.
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.
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 beta antagonist bisoprolol inhibited renal neprilysin activity and increased circulation NP levels in WKY with HF.
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.
持续性交感神经激活可导致心肌细胞损伤、心脏纤维化和心力衰竭（HF）中的左心室（LV）功能障碍进展。
本研究旨在探讨射频肾去神经（RF-RDN）对 HF 病理生物学的影响，以及肾交感神经与利钠肽（NP）代谢之间的相互作用。
自发性高血压大鼠（SHR）和正常血压 Wistar-Kyoto 大鼠（WKY）进行 45 分钟的冠状动脉结扎和再灌注 12 周。再灌注后 4 周，SHR 和 WKY 分别进行双侧 RF-RDN 或假手术-RDN。
在两种品系中进行 RF-RDN 后，LV 射血分数仍明显高于相应的假手术-RDN 大鼠，在 12 周研究结束时，两种品系的大鼠 LV 纤维化和血管功能均明显改善。RF-RDN 治疗可显著改善严重 HF 患者血管对内皮依赖性和非依赖性血管扩张剂的反应性以及血管顺应性。与假手术-RDN 相比，LV 功能的改善伴随着循环 NP 的显著升高。进一步研究发现，NP 水平升高的原因是 RF-RDN 显著抑制了 HF 中 SHR 和 WKY 的肾肽酶活性。同样，β受体阻滞剂比索洛尔的慢性治疗抑制了 HF 中 WKY 的肾肽酶活性并增加了循环 NP 水平。
本研究确定了肾神经参与降解心脏保护性 NP 的一种新的内源性途径。此外，去除肾神经对肾功能的影响可减轻肾肽酶活性，增加循环 NP 水平，减少 HF 中的心肌纤维化并改善 LV 功能。
