Effects of oxygen tension and normalization pressure on endothelin-induced constriction of human placental chorionic plate arteries.
OBJECTIVE
Fetoplacental blood vessels constrict in response to endothelin (ET-1) or reduced oxygen tension in the placental cotyledon perfused in vitro. In nonplacental resistance arteries, hypoxia and ET-1 induce constriction by promoting Ca2+ influx into smooth muscle through membrane ion channels, which include voltage-gated Ca2+ channels (VGCCs). We hypothesized that VGCCs are involved in ET-1-induced constriction of fetoplacental resistance vessels and that their contribution to constriction is enhanced at low oxygen tension.


METHODS
Chorionic plate small arteries from term placentas were studied using parallel wire myography. Arteries were normalized at 0.9 of L(5.1 kPa) ("low stretch" approximately 25 mm Hg; approximating physiologic vascular pressure) or 0.9 of L(13.3 kPa) ("high stretch" approximately 42 mm Hg) and experiments performed at oxygen tensions of 156, 38, and 15 mm Hg.


RESULTS
When chorionic plate arteries were normalized at low stretch, oxygen tension did not affect constriction to ET-1. Nifedipine (10(-4) M), a blocker of L-type VGCCs, inhibited ET-1 (EC80)-induced constriction to a similar extent at each oxygen tension (52% to 64% inhibition). In contrast, when arteries were normalized at high stretch, constriction to ET-1 was greater at 38 than at 156 or 15 mm Hg oxygen and nifedipine inhibition of ET-1-induced constriction was greater at 38 and 15 mm Hg than at 156 mm Hg oxygen.


CONCLUSIONS
VGCCs and nifedipine-insensitive processes underlie the contractile response of chorionic plate arteries to ET-1 and their relative contribution to vasoconstriction is modulated by oxygen tension when vessels are normalized at high stretch. However, contrary to our hypothesis, the response of chorionic plate arteries to ET-1 is not modulated by oxygen when vessels are normalized at physiologic pressure.
Cooper
Emma J
EJ
Maternal and Fetal Health Research Centre, St Mary's Hospital, The Medical School, University of Manchester, Manchester, UK.
Wareing
Mark
M
Greenwood
Susan L
SL
Baker
Philip N
PN
D001158:Arteries / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology*; D002823:Chorion / Q000502:physiology; D019332:Endothelin-1 / Q000502:physiology*; D005260:Female; D006801:Humans; D010100:Oxygen / Q000378:metabolism*; D010920:Placenta / Q000098:blood supply* / Q000502:physiology; D011247:Pregnancy; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000502:physiology*
D015220:Calcium Channels; D019332:Endothelin-1; D010100:Oxygen