Jewsbury S, Baker P N, Wareing M
The University of Manchester, St. Mary's Hospital, Hathersage Road, Manchester M13 0JH, UK.
Eur J Clin Invest. 2007 Jan;37(1):65-72. doi: 10.1111/j.1365-2362.2007.01749.x.
Adenosine triphosphate (ATP)-sensitive potassium channels (K(ATP)) are important modulators of vascular tone. Preliminary data from our laboratory suggests that K(ATP) channels are expressed in the fetoplacental vasculature where addition of pinacidil, a specific K(ATP) opener, promotes relaxation. We aimed to assess the effects of KRN2391 and KRN4884 on the fetoplacental vasculature, which are putative K(ATP) channel openers.
Functional activity of K(ATP) channels was assessed in chorionic plate arteries and veins using wire myography. Cromakalim-, KRN2391- and KRN4884-induced relaxations were assessed in the presence and absence of agonist-induced pretone. Cromakalim, an established K(ATP) channel opener, acted as control.
KRN2391 evoked significantly greater relaxation of chorionic plate arteries and veins than either KRN4884 or cromakalim. KRN2391-induced relaxation of precontracted arteries and veins was reduced in the presence of inhibitors of the nitric oxide pathway (L-NNA or LY83583). With KRN4884, there was no contribution of nitric oxide to the induced relaxation.
We conclude that K(ATP) channels play an important role in controlling placental vascular tone. KRN2391 induces relaxation of human placental blood vessels by activation of K(ATP) channels and via activation of nitric oxide-dependent pathways.
三磷酸腺苷（ATP）敏感性钾通道（K(ATP)）是血管张力的重要调节因子。我们实验室的初步数据表明，K(ATP)通道在胎儿-胎盘血管系统中表达，在该系统中加入特异性K(ATP)开放剂吡那地尔可促进血管舒张。我们旨在评估KRN2391和KRN4884对胎儿-胎盘血管系统的影响，它们被认为是K(ATP)通道开放剂。
使用线肌张力描记法评估绒毛膜板动脉和静脉中K(ATP)通道的功能活性。在有和没有激动剂诱导的预张力的情况下，评估克罗卡林、KRN2391和KRN4884诱导的舒张作用。已确定的K(ATP)通道开放剂克罗卡林作为对照。
KRN2391引起的绒毛膜板动脉和静脉舒张作用明显大于KRN4884或克罗卡林。在一氧化氮途径抑制剂（L-NNA或LY83583）存在的情况下，KRN2391诱导的预收缩动脉和静脉舒张作用减弱。对于KRN4884，一氧化氮对诱导的舒张作用没有贡献。
我们得出结论，K(ATP)通道在控制胎盘血管张力中起重要作用。KRN2391通过激活K(ATP)通道并通过激活一氧化氮依赖性途径诱导人胎盘血管舒张。
