Effects of magnesium and isradipine on contractile activation induced by the thromboxane A2 analog U46619 in human uteroplacental arteries in term pregnancy.

Abstract

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 F2 alpha. 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.