Nitric oxide donors mediate vasodilation in human placental arteries partly through a direct effect on potassium channels.
We have investigated the involvement of potassium channels in the NO-induced relaxation of small ET-1 precontracted arteries from placentas of normal pregnancies in the presence of the potassium channel modulating agents charybdotoxin, 4-AP, glibenclamide, TEA and the blocker of soluble guanylyl cyclase, ODQ, respectively. We have studied the effect of the NO-donor S-nitroso-N-acetylpenicillamine (SNAP) in vessels precontracted by different concentrations of potassium and we have also investigated the presence of BK(Ca) channels in placental arteries by immunohistochemistry and immunoblotting. Our results show that charybdotoxin, an inhibitor of large- and intermediate-conductance Ca(2+)-activated potassium channels, inhibits relaxation in placental arteries. In presence of both charybdotoxin and ODQ, the inhibition of relaxation was significantly stronger, which indicates that NO-induced relaxation of human placental arteries is partly mediated through cGMP, and partly through a direct effect on potassium channels of the BK(Ca) type. The NO-donor SNAP preferentially relaxes contractions induced by 75 mM K(+) as compared to 100 mM K(+). This effect profile is a unique feature of drugs acting by K(+) channel opening. The immunohistochemistry shows that BK(Ca) channels are located both in smooth muscle and in endothelium in placental arteries.
Sand
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A
Department of Women and Child Health, Division of Obstetrics and Gynaecology, Karolinska Institute and Hospital, S-171 76 Stockholm, Sweden. anna.sand@kbh.ki.se
Andersson
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E
Fried
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G
D000328:Adult; D001158:Arteries / Q000737:chemistry / Q000187:drug effects; D018999:Charybdotoxin / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology; D010920:Placenta / Q000098:blood supply* / Q000737:chemistry / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000819:agonists / Q000032:analysis / Q000187:drug effects*; D011247:Pregnancy; D011810:Quinoxalines / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology*; D014664:Vasodilation
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D011810:Quinoxalines; D018999:Charybdotoxin; D026423:S-Nitroso-N-Acetylpenicillamine; D011188:Potassium