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Journal of Trauma and Acute Care Surgery:
doi: 10.1097/TA.0b013e31828dba35
Original Articles

Hemorrhagic preconditioning improves vascular reactivity after hemorrhagic shock by activation of PKCα and PKCε via the adenosine A1 receptor in rats

Xu, Jing MD; Lan, Dan MB; Yang, Guangming MD; Li, Tao MD; Liu, Liangming MD, PhD

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Abstract

BACKGROUND: Our previous study demonstrated that protein kinase C (PKC) has an important protective role on vascular reactivity and calcium sensitivity after shock. Here, we investigated if hemorrhagic preconditioning could lessen shock-induced vascular hyporeactivity by activating PKC.

METHODS: Using hemorrhagic-shocked rats, the protective effects of different extents of hemorrhagic preconditioning on vascular reactivity and calcium sensitivity; the roles of PKCα, PKCε, and adenosine in this process; as well as hemorrhagic preconditioning-induced systemic effects were observed.

RESULTS: Hemorrhage preconditioning (particularly hemorrhage involving 5% of the total estimated blood volume implemented 30 minutes before shock) significantly improved vascular reactivity and calcium sensitivity after shock. Hemorrhage preconditioning enhanced the translocation of PKCα and PKCε from the cytoplasm to the membrane and increased the blood concentration of adenosine after shock. Antagonists of PKCα, PKCε, and the adenosine A1 receptor abolished the hemorrhagic preconditioning-induced protective effects on vascular reactivity and calcium sensitivity. The adenosine A1 receptor antagonist eliminated hemorrhagic preconditioning-induced translocation of PKCα and PKCε. Hemorrhagic preconditioning could significantly increase survival, improve hemodynamic parameters, and increase the blood flow and mitochondrial respiratory function of the liver and kidney in hemorrhagic-shock rats.

CONCLUSION: Hemorrhagic preconditioning could induce the protection of vascular reactivity and calcium sensitivity after hemorrhagic shock through the adenosine–adenosine A1 receptor–PKCα and PKCε signaling pathway and could bring further beneficial systemic effects in hemorrhagic-shock rats.

© 2013 Lippincott Williams & Wilkins, Inc.

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