Attenuated hypotensive response to proadrenomedullin N-terminal 20 peptidein pregnant rats: modulation by steroid hormones

The hypotensive effect of proadrenomedullin N-terminal 20 peptide (PAMP) wa s examined in conscious pregnant (8, 14, and 20 days of pregnancy) and nonp regnant rats. Intravenous administration of PAMP (3-60 nmol/kg) produced a dose-dependent depressor response in both pregnant and nonpregnant rats. Ho wever, the maximum decrease in blood pressure was significantly attenuated in pregnant rats in mid- and late-gestation (14 and 20 days), but not in ea rly gestation (8 days), than in nonpregnant rats. In ovariectomized rats, t he depressor responses in 17 beta-estradiol (E2)-treated, progesterone (P)- treated, and E2+-treated rats were significantly attenuated compared with t he control rats. We also demonstrated that treatment of sex hormones reduce s the depressor response to PAMP in 8-day pregnant rats. In addition, we sh owed that treatment of sex hormone receptor antagonists partially prevents the attenuation of the depressor response to PAMP in 20 day pregnant rats. These findings suggested that the hypotensive response to PAMP was more att enuated in pregnant rats in mid- and late-gestation than in nonpregnant rat s, and that the changes in depressor:response that occur at term in pregnan t rats may be mediated by sex hormones, PAMP may play some important role i n cardiovascular regulation during pregnancy. (C) 1999 Elsevier Science Inc . All rights reserved.