Abstract-Adrenomedullin is a potent vasodilatory peptide with plasma levels that increase during pregnancy. Although fetoplacental adrenomedullin levels are reported to increase in preeclampsia, maternal plasma levels may be elevated or decreased, or they may resemble those in normal pregnancy. In other hypertensive conditions, adrenomedullin increases. Therefore, we hypothesized that maternal plasma adrenomedullin levels would be higher in hypertensive pregnancies than in normotensive pregnancies and that the higher placental resistance found in preeclamptic pregnancies results from blunted activity of adrenomedullin on the vasculature. Adrenomedullin concentrations in plasma from women with normotensive pregnancies, gestational hypertension, and preeclampsia 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 maximum constriction with U46619, a thromboxane A 2 mimetic, and exposed to cumulative doses of adrenomedullin (1ϫ10 Ϫ9 to 3ϫ10 Ϫ7 mol/L). Contrary to our hypothesis, there were no significant differences in maternal plasma adrenomedullin levels among patients with normal pregnancies, gestational hypertension, and preeclampsia. Adrenomedullin significantly relaxed arteries from both normal and preeclamptic placentas, but there was no significant difference between the 2 groups. During normal pregnancy, adrenomedullin may contribute to the low placental vascular resistance. This pathway appears to be intact in preeclampsia. We conclude that the increased placental vascular resistance observed in preeclampsia is due neither to reduced adrenomedullin secretion nor to an attenuated vascular responsiveness. Moreover, unlike other hypertensive disorders, there is no compensatory rise in circulating adrenomedullin levels. (Hypertension. 2001;37:227-231.)

Pregnancy is characterized by volume expansion and vasodilation. We investigated whether the hypotensive peptide adrenomedullin (ADM) might be a significant factor in the cardiovascular adaptation to pregnancy. Rats were prepared with indwelling cannulae. Plasma ADM levels were measured by RIA before mating, at 7, 14, and 21 days of pregnancy, and at 7 days postpartum. We also investigated the effects on plasma ADM levels of administering estrogen, progesterone, and the metabolite of progesterone 3 alpha-OH-5 alpha-pregnan-20-one (3 alpha-OH-DHP); this last steroid has been implicated in altering reflex control of blood pressure and volume during pregnancy. Plasma ADM levels increased progressively during pregnancy from 123 +/- 27 pg/mL in virgin animals to 404 +/- 50 pg/mL at 21 days of pregnancy. The levels returned to pre-pregnancy values postpartum. 3 alpha-OH-DHP caused a significant rise in plasma ADM levels, whereas neither estrogen nor progesterone had any effect. We suggest that ADM may be an important contributing factor to the vasodilation associated with normal pregnancy. Active metabolites of progesterone, rather than progesterone itself, may be at least partially responsible for stimulating the release of ADM.

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