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

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 PKC alpha, PKC epsilon, 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 PKC alpha and PKC epsilon from the cytoplasm to the membrane and increased the blood concentration of adenosine after shock. Antagonists of PKC alpha, PKC epsilon, and the adenosine A(1) receptor abolished the hemorrhagic preconditioning-induced protective effects on vascular reactivity and calcium sensitivity. The adenosine A(1) receptor antagonist eliminated hemorrhagic preconditioning-induced translocation of PKC alpha and PKC epsilon. 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 adenosineYadenosine A(1) receptor-PKC alpha and PKC epsilon signaling pathway and could bring further beneficial systemic effects in hemorrhagic-shock rats. Copyright (C) 2013 by Lippincott Williams & Wilkins