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.
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.
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.
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.
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: email@example.com.