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

Abstract

Pregnancy is characterized by volumeexpansion and vasodilation. We investigated whether thehypotensive peptide adrenomedullin (ADM) might be a significantfactor in the cardiovascular adaptation to pregnancy. Rats wereprepared with indwelling cannulae. Plasma ADM levels weremeasured by RIA before mating, at 7, 14, and 21 days ofpregnancy, and at 7 days postpartum. We also investigated theeffects on plasma ADM levels of administering estrogen,progesterone, and the metabolite of progesterone3-OH-5-pregnan-20-one(3-OH-DHP); this last steroid has been implicated inaltering reflex control of blood pressure and volume duringpregnancy. Plasma ADM levels increased progressively duringpregnancy from 123 ± 27 pg/mL in virgin animals to 404 ± 50 pg/mLat 21 days of pregnancy. The levels returned to pre-pregnancyvalues postpartum.3-OH-DHP caused a significant rise in plasma ADM levels,whereas neither estrogen nor progesterone had any effect. Wesuggest that ADM may be an important contributing factor to thevasodilatation associated with normal pregnancy. Activemetabolites of progesterone, rather than progesterone itself, maybe at least partially responsible for stimulating the release ofADM.Key words: progesterone, estrogen,pregnanolone, cardiovascular system, nitric oxide.