Hemorrhagic preconditioning improves vascular reactivity after hemorrhagic shock by activation of PKC[alpha] and PKC[epsilon] via the adenosine A1 receptor in rats

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 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 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 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 adenosine–adenosine A1 receptor–PKC[alpha] and PKC[epsilon] signaling pathway and could bring further beneficial systemic effects in hemorrhagic-shock rats.