Dexmedetomidine attenuates renal ischemia–reperfusion injury through activating PI3K/Akt‐eNOS signaling via α₂ adrenoreceptors in renal microvascular endothelial cells

Abstract

Renal microvascular endothelial cells (RMECs), which are closely related to regulation of vascular reactivity and modulation of inflammation, play a crucial role in the process of renal ischemia and reperfusion (I/R) injury. Previous studies have reported the protective effects of dexmedetomidine (DEX) against renal I/R injury, but little is known about the role of DEX on RMECs. This study aimed to investigate whether DEX alleviated renal I/R injury via acting on the RMECs.Mice underwent bilateral renal artery clamping for 45 min followed by reperfusion for 48 h, and the cultured neonatal mice RMECs were subjected to hypoxia for 1 h followed by reoxygenation (H/R) for 24 h. The results suggest that DEX alleviated renal I/R injury in vivo and improved cell viability of RMECs during H/R injury in vitro. Gene sequencing revealed that the PI3K/Akt was the top enriched signaling pathway and the endothelial cells were widely involved in renal I/R injury. DEX activated phosphorylation of PI3K and Akt, increased eNOS expression, and attenuated inflammatory responses. In addition, the results confirmed the distribution of α 2 adrenoreceptor (α 2 -AR) in RMECs. Furthermore, the protective effects of DEX against renal I/R injury were abolished by α 2 -AR antagonist (atipamezole), which was partly reversed by the PI3K agonist (740 Y-P). These findings indicated that DEX protects against renal I/R injury by activating the PI3K/Akt-eNOS pathway and inhibiting inflammation responses via α 2 -AR in RMECs.

Dexmedetomidine and acute kidney injury after non-cardiac surgery: A meta-analysis with trial sequential analysis

“…Third, dexmedetomidine induces renal vasodilatation by regulating endothelial nitric oxide, which increases renal blood flow, glomerular filtration, and urine output [53,54]. Fourth, recent experimental studies showed that the attenuation of renal I/R injury by dexmedetomidine involves inhibition of ferroptosis, activation of the cholinergic anti-inflammatory pathway, and regulation of renal microvascular endothelial cells [55][56][57].…”

Drug pair of Cornus officinalis and Radix achyranthis bidentatae improves renal injury of hypertension by regulating metabolic reprogramming mediated by eNOS

“…From the perspective of metabolic reprogramming, this study elucidates the important role of eNOS in renal injury, providing us with new ideas for further prevention and treatment of hypertensive kidney injury from the perspective of metabolic reprogramming. Multiple studies [ [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] ] have found that eNOS is closely related to hypertension, kidney injury, etc. eNOS can make an decrease in PKM2, which is an important mediator for catalyzing glycolysis and increasing the conversion of phosphoenolpyruvate (PEP) to pyruvate.…”