Effects of renal denervation on monocrotaline induced pulmonary remodeling.

Qian Liu,Qijun Shan,Dasheng Lu,Jie Geng,Zhixin Jiang,Bin Zhang,Jiyang Song,Kai Wang

doi:10.18632/oncotarget.15154

Qian Liu, Qijun Shan + Show 6 more

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https://doi.org/10.18632/oncotarget.15154

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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 (RDN24h, n = 10); after 2-week of MCT injection, another ten rats received RDN treatment (RDN2w, 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 RDN24h 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.

Highlights

Pulmonary artery hypertension (PAH) is a complicated and fatal disease
At day 35, echocardiography revealed significant increases in right ventricular anterior wall thickness (RVAW, 1.56 ± 0.20 mm vs. 1.00 ± 0.25 mm, p < 0.05), Non-filling time of right ventricle (NFT; r, 133.33 ± 30.97 ms vs. 106.44 ± 18.23 ms, p < 0.05), and pulmonary ejection time (PET, 88.89 ± 4.63 vs. 73.78 ± 5.59, p < 0.05) in MCT-induced PAH group compared with the RDN24h group
renal denervation (RDN) surgery performed in the earlier stage of PAH resulted in significantly reduced RVAW thickness (1.00 ± 0.25 mm vs. 1.56 ± 0.20 mm, p < 0.05) compared with MCT group (Figure 3)

Summary

Introduction

Pulmonary artery hypertension (PAH) is a complicated and fatal disease. Progress achieved during last two decades with the introduction of oral medical therapies, the prognosis of PAH remains poor, especially in patients with advanced right heart failure [1]. It is imperative to seek potentially new therapies that prevent the development and progression of PAH. De Man F.S. et al found that the progression of PAH was accompanied by systemic RAAS overactivity [2]. We [8] and other investigators [9, 10] have reported that renal denervation (RDN) has the ability to reduce SNS activity and rebalance RAAS. It is reasonable to investigate the impact of RDN on PAH. Limited experiments have discussed the optimal time for RDN to treat PAH. Using a rat model of monocrotaline (MCT) induced pulmonary remodeling, we sought to study these isssues

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