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.
From the State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
Submitted: October 19, 2012, Revised: January 9, 2013, Accepted: January 11, 2013.
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Address for reprints: Liangming Liu, MD, PhD, State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Daping, Chongqing 400042, China; email: firstname.lastname@example.org.