Effect of adrenomedullin on placental arteries in normal and preeclamptic pregnancies

Adrenomedullin is a potent vasodilatory peptide with plasma levels that inc rease during pregnancy. Although fetoplacental adrenomedullin levels are re ported to increase in preeclampsia, maternal plasma levels may be elevated or decreased, or they may resemble those in normal pregnancy. In other hype rtensive conditions, adrenomedullin increases. Therefore, we hypothesized t hat maternal plasma adrenomedullin levels would be higher in hypertensive p regnancies than in normotensive pregnancies and that the higher placental r esistance found in preeclamptic pregnancies results from blunted activity o f adrenomedullin on the vasculature. Adrenomedullin concentrations in plasm a from women with normotensive pregnancies, gestational hypertension, and p reeclampsia were determined by radioimmunoassay. Stem villous arteries from normotensive and preeclamptic pregnancies were dissected and mounted on a wire myograph system. Arteries were first preconstricted to 80% of their ma ximum constriction with U46619, a thromboxane A(2) mimetic, and exposed to cumulative doses of adrenomedullin (1 X 10(-9) to 3 X 10(-7) mol/L). Contra ry to our hypothesis, there were no significant differences in maternal pla sma adrenomedullin levels among patients with normal pregnancies, gestation al hypertension, and preeclampsia. Adrenomedullin significantly relaxed art eries from both normal and preeclamptic placentas, but there was no signifi cant difference between the 2 groups. During normal pregnancy, adrenomedull in may contribute to the low placental vascular resistance. This pathway ap pears to be intact in preeclampsia. We conclude that the increased placenta l vascular resistance observed in preeclampsia is due neither to reduced ad renomedullin secretion nor to an attenuated vascular responsiveness. Moreov er, unlike other hypertensive disorders, there is no compensatory rise in c irculating adrenomedullin levels.