Abstract
Aims: 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 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, 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 renin-angiotensin system and brain inflammation. Central blockade of renin-angiotensin system or oxidative stress by intracerebroventricular 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 intracerebroventricular 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. Innovation: This study uncovered a novel reflex pathway between ischemic kidney and the brain that sustains renal oxidative stress and local renin-angiotensin system 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.
Key Words: Acute kidney injury, Renin-angiotensin system, Sympathetic nervous system,
Detail Information：
Cao W, Li A, Li J, Wu C, Cui S, Zhou Z, Liu Y, Wilcox CS, Hou FF. Reno-Cerebral Reflex Activates the Renin-Angiotensin System, Promoting Oxidative Stress and Renal Damage After Ischemia-Reperfusion Injury. Antioxid Redox Signal. 2017 Sep 1; 27(7):415-432. doi: 10.1089/ars.2016.6827. Epub 2017 Jan 31