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pmid28386353      Am+J+Transl+Res 2017 ; 9 (3): 1277-86
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  • HIF-1? regulates Cx40-dependent vasodilatation following hemorrhagic shock in rats #MMPMID28386353
  • Duan C; Chen K; Yang G; Li T; Liu L
  • Am J Transl Res 2017[]; 9 (3): 1277-86 PMID28386353show ga
  • HIF-1? plays an essential role in hemorrhagic shock-induced vasoconstriction. However, the underlying mechanisms remain poorly understood. Here, we studied both the role of HIF-1? 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-1? gradually increased. In the late period of shock, vasodilatation reactivity was enhanced by oligomycin, an HIF-1? inhibitor, suggesting that HIF-1? 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-1? inhibitor or an agonist. Together, these data suggest that HIF-1? may inhibit endothelium-dependent vasodilatation reactivity following hemorrhagic shock by up-regulating Cx40, especially in the late period of shock.
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