title: A Salt-Induced Reno-Cerebral Reflex Activates Renin-Angiotensin Systems and Promotes CKD Progression.
abstract: Salt intake promotes progression of CKD by uncertain mechanisms. We hypothesized that a salt-induced reno-cerebral reflex activates a renin-angiotensin axis to promote CKD. Sham-operated and 5/6-nephrectomized rats received a normal-salt (0.4%), low-salt (0.02%), or high-salt (4%) diet for 2 weeks. High salt in 5/6-nephrectomized rats increased renal NADPH oxidase, inflammation, BP, and albuminuria. Furthermore, high salt activated the intrarenal and cerebral, but not the systemic, renin-angiotensin axes and increased the activity of renal sympathetic nerves and neurons in the forebrain of these rats. Renal fibrosis was increased 2.2-fold by high versus low salt, but intracerebroventricular tempol, losartan, or clonidine reduced this fibrosis by 65%, 69%, or 59%, respectively, and renal denervation or deafferentation reduced this fibrosis by 43% or 38%, respectively (all P<0.05). Salt-induced fibrosis persisted after normalization of BP with hydralazine. These data suggest that the renal and cerebral renin-angiotensin axes are interlinked by a reno-cerebral reflex that is activated by salt and promotes oxidative stress, fibrosis, and progression of CKD independent of BP.
authors: State Key Laboratory of Organ Failure Research, National Clinical Research Center for Kidney Disease, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China; and.
authors: Wei
authors: W
authors: Cao
authors: State Key Laboratory of Organ Failure Research, National Clinical Research Center for Kidney Disease, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China; and.
authors: Aiqing
authors: A
authors: Li
authors: State Key Laboratory of Organ Failure Research, National Clinical Research Center for Kidney Disease, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China; and.
authors: Liangliang
authors: L
authors: Wang
authors: State Key Laboratory of Organ Failure Research, National Clinical Research Center for Kidney Disease, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China; and.
authors: Zhanmei
authors: Z
authors: Zhou
authors: State Key Laboratory of Organ Failure Research, National Clinical Research Center for Kidney Disease, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China; and.
authors: Zhengxiu
authors: Z
authors: Su
authors: State Key Laboratory of Organ Failure Research, National Clinical Research Center for Kidney Disease, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China; and.
authors: Wei
authors: W
authors: Bin
authors: Center for Hypertension, Kidney, and Vascular Research, Georgetown University, Washington, DC.
authors: Christopher S
authors: CS
authors: Wilcox
authors: State Key Laboratory of Organ Failure Research, National Clinical Research Center for Kidney Disease, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China; and ffhouguangzhou@163.com.
authors: Fan Fan
authors: FF
authors: Hou
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005355:Fibrosis / Q000473:pathology; D006830:Hydralazine / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D009392:Nephrectomy; D018384:Oxidative Stress / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012016:Reference Values; D012018:Reflex / Q000502:physiology; D012079:Renal Circulation / Q000502:physiology; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D012965:Sodium Chloride / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D006830:Hydralazine; D012965:Sodium Chloride
keywords: brain; kidney; renal fibrosis; renin-angiotensin system; salt
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