Adrenomedullin attenuates the hypertension in hypertensive pregnant rats induced by N-G-nitro-L-arginine methyl ester

We examined the effect of adrenomedullin on the cardiovascular system of an animal model for preeclampsia. An inhibitor of nitric oxide synthase, N-G- nitro-L-arginine methyl ester (L-NAME), was infused subcutaneously into rat s at a constant rate from day 14 of pregnancy to make an animal model for p reeclampsia. Adrenomedullin was continuously infused intravenously at a dos e of 3 or 10 pmol/h from day 17 of pregnancy. The basal systolic blood pres sure was significantly higher in the L-NAME treated rats than in the contro l rats. The adrenomedullin administration at day 19 of pregnancy showed a s ignificant decrease in the blood pressure in the L-NAME treated rats than i n vehicle rats during infusion. The blood pressure of normal pregnant rats did not significantly decrease by adrenomedullin infusion. The adrenomedull in decreased pup mortality of the L-NAME treated rats. Adrenomedullin atten uated the L-NAME induced hypertension and pup mortality. On the other hand, adrenomedullin administration in both pregnant rats in early gestation (5- 11 days of pregnancy) and in non-pregnant rats did not show any significant effect on L-NAME-induced hypertension. The adrenomedullin mRNA level was p redominantly expressed at high levels in the ovary, uterus and placenta, bu t at low levels in other tissues in pregnant rats in late gestation. The ad renomedullin mRNA level of the L-NAME treated rats in placenta decreased mo re than in the normal pregnant rats in late gestation (P < 0.05). These fin dings suggest that the adrenomedullin might play an important role in the r egulation of the cardiovascular system of the mother and fetoplacental unit in rats. (C) 1999 Elsevier Science B.V. All rights reserved.