Yang Guangming, Peng Xiaoyong, Wu Yue, Li Tao, Liu Liangming
State Key Laboratory of Trauma, Burns, and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
State Key Laboratory of Trauma, Burns, and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China
Am J Physiol Cell Physiol. 2017 Oct 1;313(4):C362-C370. doi: 10.1152/ajpcell.00258.2016. Epub 2017 Aug 9.
We examined the roles played by gap junctions (GJs) and the GJ channel protein connexin 43 (Cx43) in arginine vasopressin (AVP)-induced vasoconstriction after hemorrhagic shock and their relationship to Rho kinase (ROCK) and protein kinase C (PKC). The results showed that AVP induced an endothelium-independent contraction in rat superior mesenteric arteries (SMAs). Blocking the GJs significantly decreased the contractile response of SMAs and vascular smooth muscle cells (VSMCs) to AVP after shock and hypoxia. The selective Cx43-mimetic peptide inhibited the vascular contractile effect of AVP after shock and hypoxia. AVP restored hypoxia-induced decrease of Cx43 phosphorylation at Ser and gap junctional communication in VSMCs. Activation of RhoA with U-46619 increased the contractile effect of AVP. This effect was antagonized by the ROCK inhibitor Y27632 and the Cx43-mimetic peptide. In contrast, neither an agonist nor an inhibitor of PKC had significant effects on AVP-induced contraction after hemorrhagic shock. In addition, silencing of Cx43 with siRNA blocked the AVP-induced increase of ROCK activity in hypoxic VSMCs. In conclusion, AVP-mediated vascular contractile effects are endothelium and myoendothelial gap junction independent. Gap junctions between VSMCs, gap junctional communication, and Cx43 phosphorylation at Ser play important roles in the vascular effects of AVP. RhoA/ROCK, but not PKC, is involved in this process.
我们研究了缝隙连接（GJ）和缝隙连接通道蛋白连接蛋白43（Cx43）在失血性休克后精氨酸加压素（AVP）诱导的血管收缩中的作用，以及它们与Rho激酶（ROCK）和蛋白激酶C（PKC）的关系。结果表明，AVP可诱导大鼠肠系膜上动脉（SMA）产生不依赖内皮的收缩。阻断缝隙连接可显著降低休克和缺氧后SMA及血管平滑肌细胞（VSMC）对AVP的收缩反应。选择性Cx43模拟肽可抑制休克和缺氧后AVP的血管收缩作用。AVP可恢复缺氧诱导的VSMC中Cx43丝氨酸磷酸化降低及缝隙连接通讯。用U-46619激活RhoA可增强AVP的收缩作用。ROCK抑制剂Y27632和Cx43模拟肽可拮抗这种作用。相反，PKC的激动剂或抑制剂对失血性休克后AVP诱导的收缩均无显著影响。此外，用小干扰RNA（siRNA）沉默Cx43可阻断缺氧VSMC中AVP诱导的ROCK活性增加。总之，AVP介导的血管收缩作用不依赖内皮和肌内皮缝隙连接。VSMC之间的缝隙连接、缝隙连接通讯以及Cx43丝氨酸磷酸化在AVP的血管效应中起重要作用。RhoA/ROCK而非PKC参与了这一过程。
