title: Bilateral Renal Denervation Ameliorates Isoproterenol-Induced Heart Failure through Downregulation of the Brain Renin-Angiotensin System and Inflammation in Rat.
abstract: Heart failure (HF) is characterized by cardiac dysfunction along with autonomic unbalance that is associated with increased renin-angiotensin system (RAS) activity and elevated levels of proinflammatory cytokines (PICs). Renal denervation (RD) has been shown to improve cardiac function in HF, but the protective mechanisms remain unclear. The present study tested the hypothesis that RD ameliorates isoproterenol- (ISO-) induced HF through regulation of brain RAS and PICs. Chronic ISO infusion resulted in remarked decrease in blood pressure (BP) and increase in heart rate and cardiac dysfunction, which was accompanied by increased BP variability and decreased baroreflex sensitivity and HR variability. Most of these adverse effects of ISO on cardiac and autonomic function were reversed by RD. Furthermore, ISO upregulated mRNA and protein expressions of several components of the RAS and PICs in the lamina terminalis and hypothalamic paraventricular nucleus, two forebrain nuclei involved in cardiovascular regulations. RD significantly inhibited the upregulation of these genes. Either intracerebroventricular AT1-R antagonist, irbesartan, or TNF-αinhibitor, etanercept, mimicked the beneficial actions of RD in the ISO-induced HF. The results suggest that the RD restores autonomic balance and ameliorates ISO-induced HF and that the downregulated RAS and PICs in the brain contribute to these beneficial effects of RD.
authors.affiliation: Department of Physiology and Life Science Research Center, Hebei North University, Diamond South Road 11, Zhangjiakou City, Hebei 075000, China.
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Li
authors.affiliation: Department of Physiology and Life Science Research Center, Hebei North University, Diamond South Road 11, Zhangjiakou City, Hebei 075000, China.
authors.forename: Ai-Yuan
authors.initials: AY
authors.lastname: Cheng
authors.affiliation: Department of Physiology and Life Science Research Center, Hebei North University, Diamond South Road 11, Zhangjiakou City, Hebei 075000, China.
authors.forename: Yan-Li
authors.initials: YL
authors.lastname: Huo
authors.affiliation: Department of Physiology and Life Science Research Center, Hebei North University, Diamond South Road 11, Zhangjiakou City, Hebei 075000, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Physiology and Life Science Research Center, Hebei North University, Diamond South Road 11, Zhangjiakou City, Hebei 075000, China.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Life Science Research Center, Hebei North University, Diamond South Road 11, Zhangjiakou City, Hebei 075000, China.
authors.forename: Zhi-Qin
authors.initials: ZQ
authors.lastname: Fang
authors.affiliation: Department of Physiology and Life Science Research Center, Hebei North University, Diamond South Road 11, Zhangjiakou City, Hebei 075000, China.
authors.forename: Hong-Sheng
authors.initials: HS
authors.lastname: Sun
authors.affiliation: Department of Physiology and Life Science Research Center, Hebei North University, Diamond South Road 11, Zhangjiakou City, Hebei 075000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Peng
authors.affiliation: Department of Physiology and Life Science Research Center, Hebei North University, Diamond South Road 11, Zhangjiakou City, Hebei 075000, China.
authors.forename: Jin-Shun
authors.initials: JS
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Life Science Research Center, Hebei North University, Diamond South Road 11, Zhangjiakou City, Hebei 075000, China.
authors.forename: Hai-Ping
authors.identifier: 0000-0002-1198-9024
authors.initials: HP
authors.lastname: Wang
authors.affiliation: Department of Physiology and Life Science Research Center, Hebei North University, Diamond South Road 11, Zhangjiakou City, Hebei 075000, China.
authors.forename: Bao-Jian
authors.identifier: 0000-0002-6326-0075
authors.initials: BJ
authors.lastname: Xue
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D003714:Denervation; D015536:Down-Regulation; D006333:Heart Failure / Q000139:chemically induced*; D007249:Inflammation / Q000378:metabolism*; D007545:Isoproterenol / Q000009:adverse effects*; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D007545:Isoproterenol