Abstract:Background Adenosine triphosphate (ATP)‐sensitive potassium channels (KATP) are important modulators of vascular tone. Preliminary data from our laboratory suggests that KATP channels are expressed in the fetoplacental vasculature where addition of pinacidil, a specific KATP opener, promotes relaxation. We aimed to assess the effects of KRN2391 and KRN4884 on the fetoplacental vasculature, which are putative KATP channel openers.Materials and methods Functional activity of KATP 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 KATP channel opener, acted as control.Results 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 inhibitiors of the nitric oxide pathway (L‐NNA or LY83583). With KRN4884, there was no contribution of nitric oxide to the induced relaxation.Conclusions We conclude that KATP channels play an important role in controlling placental vascular tone. KRN2391 induces relaxation of human placental blood vessels by activation of KATP channels and via activation of nitric oxide‐dependent pathways.