title: HIF-1α regulates Cx40-dependent vasodilatation following hemorrhagic shock in rats.
abstract: HIF-1α plays an essential role in hemorrhagic shock-induced vasoconstriction. However, the underlying mechanisms remain poorly understood. Here, we studied both the role of HIF-1α in regulating vasodilatation, and the involvement of Cx40 in this process. We found that endothelium-dependent vasodilatation exhibited an overall decline after hemorrhagic shock: at the beginning of shock vasodilatation reactivity significantly decreased, followed by a slight increase from 0.5 h to 2 h after shock. After 2 h vasodilatation dropped again. Throughout this process, protein levels of HIF-1α gradually increased. In the late period of shock, vasodilatation reactivity was enhanced by oligomycin, an HIF-1α inhibitor, suggesting that HIF-1α may promote vasoconstriction. Moreover, in the late period of shock Cx40 levels gradually increased and exhibited a negative correlation with endothelium-dependent vasoconstriction reactivity. Furthermore, Cx40 AODN significantly improved vasoconstriction reactivity and could be regulated by either an HIF-1α inhibitor or an agonist. Together, these data suggest that HIF-1α may inhibit endothelium-dependent vasodilatation reactivity following hemorrhagic shock by up-regulating Cx40, especially in the late period of shock.
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 400042, China.
authors.forename: Chenyang
authors.initials: C
authors.lastname: Duan
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 400042, China.
authors.forename: Ken
authors.initials: K
authors.lastname: Chen
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 400042, China.
authors.forename: Guangming
authors.initials: G
authors.lastname: Yang
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 400042, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
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 400042, China.
authors.forename: Liangming
authors.initials: L
authors.lastname: Liu
keywords: Cx40; HIF-1α; endothelium-dependent vasodilatation reactivity; hemorrhagic shock