EFFECTS OF MAGNESIUM AND ISRADIPINE ON CONTRACTILE ACTIVATION INDUCED BY THE THROMBOXANE-A2 ANALOG U46619 IN HUMAN UTEROPLACENTAL ARTERIES IN TERM PREGNANCY

The effects of Mg++ and the dihydropyridine calcium channel blocker isradipine on contractions induced by the thromboxane A2 mimetic U46619 were studied in isolated human uteroplacental arteries. In all preparations investigated U46619 10-10 to 10-6 mol/L induced concentration-related contractile responses. In maternal vessels U46619 produced a biphasic concentration-response curve, whereas the compound in fetal vessels produced a sigmoid concentration-response curve parallel to that of prostaglandin F2α. Mg++ (1.0 to 6.0 mmol/L) and isradipine (10-10 to 10-5 mol/L) both relaxed U46619-induced contractions by up to about 40%. In preparations precontracted by U46619 and exposed to isradipine 10-6 mol/L, addition of Mg++ 6.0 mmol/L consistently produced a further small relaxation. Removal of the endothelium or pretreatment with indomethacin 10-6 mol/L or digoxin 10-6 mol/L did not influence the inhibition produced by Mg++ or isradipine. In vessels pretreated in Ca++-free medium Mg++ 6.0 mmol/L depressed and isradipine abolished responses to Ca++ (0.01 to 4.0 mmol/L) after depolarization with K+ 124 mmol/L. In maternal and fetal arteries stimulated with U46619, however, Mg++ 6.0 mmol/L and isradipine 10-6 mol/L produced a similar, partial inhibition of responses to Ca++ (0.01 to 4.0 mmol/L). Mg++ seems to inhibit transmembrane Ca++ influx, although less efficiently than the dihydropyridine calcium antagonist isradipine. In addition, Mg++ may interfere with Ca++ at intracellular binding sites. Provided that preeclampsia comprises enhanced vascular actions of thromboxane A2, the present results support the established use of Mg++ in the treatment of this condition and suggest that calcium antagonists are of potential benefit. © 1990.