title: Pinacidil pretreatment improves vascular reactivity after shock through PKCα and PKCε in rats.
abstract: We investigated the beneficial effect of pinacidil pretreatment on vascular reactivity, calcium sensitivity, and animal survival after hemorrhagic shock, its relationship to protein kinase Cα (PKCα), protein kinase Cε (PKCε), and adenosine. Using hemorrhagic shock rats, the protective effects of different extents of pinacidil pretreatment on vascular reactivity and in which the roles of PKCα, PKCε, and adenosine were observed. Pinacidil pretreatment significantly improved shock-induced decrease of vascular reactivity of superior mesenteric artery, which was antagonized by the PKCα antagonist Gö-6976 (5 × 10 mole/L) and PKCε pseudosubstrate inhibitory peptide (1 × 10 mole/L). Pinacidil pretreatment induced the translocation of PKCα and PKCε from the cytoplasm to the membrane. This translocation of PKCα and PKCε was eliminated by adenosine A1 receptor antagonist DPCPX (1 × 10 mole/L). As compared with simple fluid resuscitation, combination with pinacidil pretreatment significantly improved the vascular reactivity and survival rate of hemorrhagic-shocked rats. These results suggested that pinacidil pretreatment could induce good protective effects on vascular reactivity and calcium sensitivity after hemorrhagic shock mainly through the activation of PKCα and PKCε via adenosine A1 receptor, and this protective effect made an important contribution to the overall outcome of shock therapy.
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Guangming
authors.initials: G
authors.lastname: Yang
authors.forename: Liangming
authors.initials: L
authors.lastname: Liu
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005440:Fluid Therapy / Q000379:methods; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000378:metabolism; D020110:Pinacidil / Q000494:pharmacology*; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000187:drug effects / Q000378:metabolism; D012151:Resuscitation / Q000379:methods; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy; D015996:Survival Rate; D014665:Vasodilator Agents / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
chemical_list: D043682:Receptor, Adenosine A1; D014665:Vasodilator Agents; D014970:Xanthines; D020110:Pinacidil; C051360:1,3-dipropyl-8-cyclopentylxanthine; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D000241:Adenosine; D002118:Calcium