ACTIONS OF MAGNESIUM, NIFEDIPINE AND CLONIDINE ON THE FETAL VASCULATURE OF THE HUMAN PLACENTA

The anticonvulsant magnesium and the antihypertensives clonidine and n ifedipine are extensively used for the clinical treatment of preeclamp sia and eclampsia. Little, however, is known about the possible effect s of these agents on human fetal-placental vascular resistance, We the refore examined the actions of these agents on the human fetal placent al vascular bed in vitro relating the concentrations causing any vasoa ctive effects to the maternal blood levels attained during treatment. Placentas (n=24) were obtained within 20 minutes of delivery from wome n (aged 30.2+/-0.9 years). In each a placental lobule was bilaterally perfused with Krebs' solution (5 mL/minute, 37 degrees C, 95% O-2, 5% CO2) and fetal arterial inflow pressure (FAP) monitored. Submaximal va soconstriction of the fetal vascular bed was induced by continuous inf usion of prostaglandin F-2 alpha (4.2 +/- 0.5 mu M) which increased FA P 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 ex amined. Magnesium (0.3-100 mM) (n=4) dilated the placental fetal circu lation 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 mu M). 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), whe n compared to controls. Thus in concentrations likely to be therapeuti cally 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 .