Relaxation of human placental arteries and veins by ATP-sensitive potassium channel openers.
BACKGROUND
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.


METHODS
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.


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 inhibitors 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 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.
Jewsbury
S
S
The University of Manchester, St. Mary's Hospital, Hathersage Road, Manchester M13 0JH, UK.
Baker
P N
PN
Wareing
M
M
D000255:Adenosine Triphosphate / Q000627:therapeutic use*; D000818:Animals; D001158:Arteries / Q000502:physiology*; D005260:Female; D006801:Humans; D009126:Muscle Relaxation / Q000187:drug effects; D010920:Placenta / Q000098:blood supply* / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D014664:Vasodilation / Q000502:physiology; D014680:Veins / Q000502:physiology*
C096484:KRN 4884; D015221:Potassium Channels; D011725:Pyridines; D000255:Adenosine Triphosphate