title: Reno-Cerebral Reflex Activates the Renin-Angiotensin System, Promoting Oxidative Stress and Renal Damage After Ischemia-Reperfusion Injury.
abstract: OBJECTIVE
  A kidney-brain interaction has been described in acute kidney injury, but the mechanisms are uncertain. Since we recently described a reno-cerebral reflex, we tested the hypothesis that renal ischemia-reperfusion injury (IRI) activates a sympathetic reflex that interlinks the renal and cerebral renin-angiotensin axis to promote oxidative stress and progression of the injury.
  
  
  RESULTS
  Bilateral ischemia-reperfusion activated the intrarenal and cerebral, but not the circulating, renin-angiotensin system (RAS), increased sympathetic activity in the kidney and the cerebral sympathetic regulatory regions, and induced brain inflammation and kidney injury. Selective renal afferent denervation with capsaicin or renal denervation significantly attenuated IRI-induced activation of central RAS and brain inflammation. Central blockade of RAS or oxidative stress by intracerebroventricular (ICV) losartan or tempol reduced the renal ischemic injury score by 65% or 58%, respectively, and selective renal afferent denervation or reduction of sympathetic tone by ICV clonidine decreased the score by 42% or 52%, respectively (all p < 0.05). Ischemia-reperfusion-induced renal damage and dysfunction persisted after controlling blood pressure with hydralazine.
  
  
  METHODS
  This study uncovered a novel reflex pathway between ischemic kidney and the brain that sustains renal oxidative stress and local RAS activation to promote ongoing renal damage.
  
  
  CONCLUSIONS
  These data suggest that the renal and cerebral renin-angiotensin axes are interlinked by a reno-cerebral sympathetic reflex that is activated by ischemia-reperfusion, which contributes to ischemia-reperfusion-induced brain inflammation and worsening of the acute renal injury. Antioxid. Redox Signal. 27, 415-432.
authors.affiliation: 1 Division of Nephrology, Nanfang Hospital, Southern Medical University , State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou, P.R. China .
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.affiliation: 1 Division of Nephrology, Nanfang Hospital, Southern Medical University , State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou, P.R. China .
authors.forename: Aiqing
authors.initials: A
authors.lastname: Li
authors.affiliation: 1 Division of Nephrology, Nanfang Hospital, Southern Medical University , State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou, P.R. China .
authors.forename: Jiawen
authors.initials: J
authors.lastname: Li
authors.affiliation: 1 Division of Nephrology, Nanfang Hospital, Southern Medical University , State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou, P.R. China .
authors.forename: Chunyi
authors.initials: C
authors.lastname: Wu
authors.affiliation: 1 Division of Nephrology, Nanfang Hospital, Southern Medical University , State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou, P.R. China .
authors.forename: Shuang
authors.initials: S
authors.lastname: Cui
authors.affiliation: 1 Division of Nephrology, Nanfang Hospital, Southern Medical University , State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou, P.R. China .
authors.forename: Zhanmei
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: 1 Division of Nephrology, Nanfang Hospital, Southern Medical University , State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou, P.R. China .
authors.forename: Youhua
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 2 Hypertension, Kidney and Vascular Research Center, Georgetown University , Washington, District of Columbia.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Wilcox
authors.affiliation: 1 Division of Nephrology, Nanfang Hospital, Southern Medical University , State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou, P.R. China .
authors.forename: Fan Fan
authors.initials: FF
authors.lastname: Hou
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism* / Q000628:therapy; D000818:Animals; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System; D015427:Reperfusion Injury / Q000150:complications*; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000502:physiology*
keywords: acute kidney injury; brain; kidney; renin-angiotensin system; sympathetic nervous system