Actions of magnesium, nifedipine and clonidine on the fetal vasculature of the human placenta.
The anticonvulsant magnesium and the antihypertensives clonidine and nifedipine are extensively used for the clinical treatment of preeclampsia and eclampsia. Little, however, is known about the possible effects of these agents on human fetal-placental vascular resistance. We therefore examined the actions of these agents on the human fetal placental vascular bed in vitro relating the concentrations causing any vasoactive effects to the maternal blood levels attained during treatment. Placentas (n = 24) were obtained within 20 minutes of delivery from women (aged 30.2 +/- 0.9 years). In each a placental lobule was bilaterally perfused with Krebs' solution (5 mL/minute, 37 degrees C, 95% O2, 5% CO2) and fetal arterial inflow pressure (FAP) monitored. Submaximal vasoconstriction of the fetal vascular bed was induced by continuous infusion of prostaglandin F2 alpha (4.2 +/- 0.5 microM) which increased FAP from 25.9 +/- 3.9 to 95.1 +/- 6.2 mm Hg. Using a group of placentas for each drug, the effects of MgCl2, nifedipine and clonidine, were examined. Magnesium (0.3-100 mM) (n = 4) dilated the placental fetal circulation with an IC50 of 8.1 mM and a maximal response of 89.7 +/- 3.6% (n = 4). This effect of Mg2+ was not changed during concomitant infusion of the cyclo-oxygenase inhibitor, indomethacin (3 microM). Nifedipine (3-10,000 nM) also produced vasodilatation (maximum response 42 +/- 9%, n = 5). Clonidine (3-1,000 nM) caused no significant change (p < 0.05 n = 5) in vascular resistance (maximum response 11.2-5.7%) relaxation), when compared to controls. Thus in concentrations likely to be therapeutically present in maternal blood, magnesium causes a greater degree of placental fetal vasodilatation than does nifedipine, whereas clonidine is unlikely to have any effect on fetal placental vascular resistance.
David
R
R
Department of Obstetrics and Gynaecology, Atma Jaya Hospital, Jakarta, Indonesia.
Leitch
I M
IM
Read
M A
MA
Boura
A L
AL
Walters
W A
WA
D000959:Antihypertensive Agents / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000098:blood supply; D006801:Humans; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology*; D010920:Placenta / Q000098:blood supply* / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D000959:Antihypertensive Agents; D008274:Magnesium; D009543:Nifedipine; D003000:Clonidine