Effects of renal denervation on monocrotaline induced pulmonary remodeling

// Qian Liu 1, * , Jiyang Song 2 , Dasheng Lu 1, * , Jie Geng 1 , Zhixin Jiang 1 , Kai Wang 1 , Bin Zhang 1 and Qijun Shan 1 1 Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China 2 Department of Cardiology, Gansu Provincial Hospital, Lanzhou, China * These authors contributed equally to this work Correspondence to: Qijun Shan, email: qjshan@njmu.edu.cn Keywords: renal denervation, monocrotaline, pulmonary remodeling Received: November 04, 2016      Accepted: January 24, 2017      Published: February 07, 2017 ABSTRACT Pulmonary artery hypertension (PAH) is a rapidly progressive disorder, which leads to right heart failure and even death. Overactivity of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system accounts for the development and progression of PAH. The role of renal denervation (RDN) in different periods of PAH has not been fully elucidated. A single intraperitoneal injection of monocrotaline (MCT, 60 mg/kg) was used to induce pulmonary remodeling in male Sprague Dawley rats ( n = 40). After 24-hour of MCT administration, a subset of rats underwent RDN (RDN 24h , n = 10); after 2-week of MCT injection, another ten rats received RDN treatment (RDN 2w , n = 10) and the left 20 rats were divided to MCT group with sham RDN operation (MCT, n = 20). Eight rats in Control group received intraperitoneal injection of normal saline (60 mg/kg) once and sham RDN surgery. After 35 days, tissue and blood samples were collected. Histological analysis demonstrated that the collagen volume fraction of right ventricle, lung tissue and pulmonary vessel reduced significantly in RDN 24h group but not in the RDN2w group, compared with MCT group. Moreover, the earlier RDN treatment significantly decreased SNS activity and blunted RAAS activation. Importantly, RDN treatment significantly improved the survival rate. In summary, earlier RDN treatment could attenuate cardio-pulmonary fibrosis and therefore might be a promising approach to prevent the development of PAH.