Enhanced Cerebrovascular Response To Angiotensin ? In Mice With Renal-ischemia Reperfusion Injury

Aim:Acute kidney injury(AKI)is a common complication with high morbidity and mortality.Increasing evidence suggests that AKI mediates a systemic response that can lead to multiple organ failures.The aims of this study are to investigate the changes of cerebrovascular response to angiotensin ? in mice with renal-ischemia reperfusion injury and the roles of FGF 2 in these effects.Methods:The bilateral renal pedicle was clipped 30 min in male C57B1/6 mice and recovered for 24 h to produce AKI models,Some of the mice with AKI were given fibroblast growth factor receptor(FGFR)1/2/3 inhibitor BGJ398(10 mg/kg)through intragastric administration at 20th of 24 h AKI.Three groups such as sham,AKI and AKI+BGJ398 group were involved.Draw blood from post eyeball after 24 h and measured the level of serum creatinine and urea nitrogen.After hematoxylin-eosin staining,the pathomorphological changes of kidney were observed.Brain basilar artery and posterior communicating artery were dissected,and the responses of those arteries to Ang ? were tested by DMT.The mRNA expressions of FGF 2,fibroblast growth factor binding protein 1(FGFBP 1),fibroblast growth factor receptor(FGFR),angiotensin receptor(AT1R,AT2R),PLC? and PLC? were evaluated by real-time PCR.Results:The Ang ? responses were enhanced in brain vessels after AKI.Pretreatment with FGF 2 and FGFBP 1 could amplify this effect.Blockades of FGFR in vivo and in vitro could blunt the Ang ? responses in cerebral arteries in mice enhanced by FGF 2 and FGFBP 1 and/or AKI.The serum FGF 2 concentration were increased in mice after AKI,and the expression of mRNA for FGFR and PLC in AKI were increased compared to the sham group.Conclusion:We found that the Ang II responses were enhanced in brain vessels after AKI and this effect was amplified by treatment with FGF 2 and FGFBP 1.We conclude that the Ang ? and FGFR signaling pathway may be one of the reasons for brain injury after AKI.