title: Renal denervation attenuates aldosterone expression and associated cardiovascular pathophysiology in angiotensin II-induced hypertension.
abstract: The sympathetic nervous system interacts with the renin-angiotensin-aldosterone system (RAAS) contributing to cardiovascular diseases. In this study, we sought to determine if renal denervation (RDN) inhibits aldosterone expression and associated cardiovascular pathophysiological changes in angiotensin II (Ang II)-induced hypertension. Bilateral RDN or SHAM operation was performed before chronic 14-day Ang II subcutaneous infusion (200ng/kg/min) in male Sprague-Dawley rats. Bilateral RDN blunted Ang II-induced hypertension and ameliorated the mesenteric vascular dysfunction. Cardiovascular hypertrophy in response to Ang II was significantly attenuated by RDN as shown by histopathology and transthoracic echocardiography. Moreover, Ang II-induced vascular and myocardial inflammation and fibrosis were suppressed by RDN with concurrent decrease in fibronectin and collagen deposition, macrophage infiltration, and MCP-1 expression. Interestingly, RDN also inhibited Ang II-induced aldosterone expression in the plasma, kidney and heart. This was associated with the reduction of calcitonin gene-related peptide (CGRP) in the adrenal gland. Ang II promoted aldosterone secretion which was partly attenuated by CGRP in the adrenocortical cell line, suggesting a protective role of CGRP in this model. Activation of transforming growth factor-β (TGF-β)/Smad and mitogen-activated protein kinases (MAPKs) signaling pathway was both inhibited by RDN especially in the heart. These results suggest that the regulation of the renal sympathetic nerve in Ang II-induced hypertension and associated cardiovascular pathophysiological changes is likely mediated by aldosterone, with CGRP involvement.
authors.affiliation: Department of Hypertension, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Institute of Hypertension, Shanghai, China.
authors.forename: Mo-Na
authors.initials: MN
authors.lastname: Hong
authors.affiliation: Department of Hypertension, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Institute of Hypertension, Shanghai, China.|Laboratory of Vascular Biology and Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Li
authors.affiliation: Department of Hypertension, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Institute of Hypertension, Shanghai, China.
authors.forename: Dong-Rui
authors.initials: DR
authors.lastname: Chen
authors.affiliation: Department of Hypertension, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Institute of Hypertension, Shanghai, China.|Laboratory of Vascular Biology and Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Cheng-Chao
authors.initials: CC
authors.lastname: Ruan
authors.affiliation: Department of Hypertension, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Institute of Hypertension, Shanghai, China.
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Xu
authors.affiliation: Department of Hypertension, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Institute of Hypertension, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Hypertension, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Institute of Hypertension, Shanghai, China.
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Wu
authors.affiliation: Department of Hypertension, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Institute of Hypertension, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Hypertension, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Institute of Hypertension, Shanghai, China.
authors.forename: Ding-Liang
authors.initials: DL
authors.lastname: Zhu
authors.affiliation: Department of Hypertension, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Institute of Hypertension, Shanghai, China.|Laboratory of Vascular Biology and Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ping-Jin
authors.initials: PJ
authors.lastname: Gao
mesh_terms: D000450:Aldosterone / Q000097:blood / Q000378:metabolism*; D000804:Angiotensin II; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D045744:Cell Line, Tumor; D003714:Denervation; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000294:innervation / Q000378:metabolism*; D008297:Male; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000804:Angiotensin II; D000450:Aldosterone; D015740:Calcitonin Gene-Related Peptide
keywords: Pathology Section; aldosterone; angiotensin II; remodeling; renal denervation; sympathetic nervous system