Effect of pregnancy and steroid hormones on plasma adrenomedullin levels in the rat.

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.