Oxygen tension and normalisation pressure modulate nifedipine-sensitive relaxation of human placental chorionic plate arteries.
Fetoplacental blood vessel constriction in response to reduced oxygenation has been demonstrated in placenta perfused in vitro. In pulmonary vessels, hypoxic vasoconstriction involves Ca2+ influx into smooth muscle through membrane ion channels including voltage-gated Ca2+ channels (VGCCs). We hypothesised that VGCCs are involved in agonist-induced constriction of fetoplacental resistance vessels and that their contribution is modulated by oxygen. Chorionic plate small arteries were studied using wire myography. Arteries were normalised at high (0.9 of L(13.3 kPa)) or low (0.9 of L(5.1 kPa)) stretch and experiments performed at 156, 38 or 15 mmHg oxygen. At low stretch, U46619 (thromboxane-mimetic) or KCl (smooth muscle depolarisation) constriction was greater at 38 than 156 or 15 mmHg oxygen. An L-type VGCC blocker nifedipine, inhibited KCl constriction by >85% but was less effective in U46619 constrictions (43-67%). At high stretch, nifedipine inhibition of KCl- and U46619-induced constriction was less at 15 than 38 or 156 mmHg oxygen. Oxygen did not affect constriction to U46619 or nifedipine-induced relaxation when vessels were normalised at high stretch. In conclusion, oxygen modulates chorionic plate arterial constriction at low stretch but regulation is lost at high stretch. U46619 constriction is underlain by VGCCs and nifedipine-insensitive processes; their relative contribution is influenced by oxygen.
Cooper
E J
EJ
Maternal and Fetal Health Research Centre, University of Manchester, St Mary's Hospital, Hathersage Road, Manchester M13 0JH, UK.
Wareing
M
M
Greenwood
S L
SL
Baker
P N
PN
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects; D020746:Calcium Channels, L-Type / Q000187:drug effects; D002824:Chorionic Villi / Q000098:blood supply* / Q000187:drug effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009543:Nifedipine / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D011247:Pregnancy; D011312:Pressure; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D020746:Calcium Channels, L-Type; D014665:Vasodilator Agents; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D009543:Nifedipine; D010100:Oxygen