Attenuated hypotensive response to proadrenomedullin N-terminal 20 peptide in pregnant rats: modulation by steroid hormones.
The hypotensive effect of proadrenomedullin N-terminal 20 peptide (PAMP) was examined in conscious pregnant (8, 14, and 20 days of pregnancy) and nonpregnant rats. Intravenous administration of PAMP (3-60 nmol/kg) produced a dose-dependent depressor response in both pregnant and nonpregnant rats. However, the maximum decrease in blood pressure was significantly attenuated in pregnant rats in mid- and late-gestation (14 and 20 days), but not in early gestation (8 days), than in nonpregnant rats. In ovariectomized rats, the depressor responses in 17beta-estradiol (E2)-treated, progesterone (P)-treated, and E2+P-treated rats were significantly attenuated compared with the control rats. We also demonstrated that treatment of sex hormones reduces the depressor response to PAMP in 8-day pregnant rats. In addition, we showed 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 attenuated in pregnant rats in mid- and late-gestation than in nonpregnant rats, and that the changes in depressor response that occur at term in pregnant rats may be mediated by sex hormones. PAMP may play some important role in cardiovascular regulation during pregnancy.
Makino
I
I
Department of Obstetrics and Gynecology, School of Medicine, Fukuoka University, Japan.
Makino
Y
Y
Kangawa
K
K
Shibata
K
K
D053607:Adrenomedullin; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology; D007022:Hypotension / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology; D015735:Mifepristone / Q000494:pharmacology; D010052:Ovariectomy; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D010455:Peptides; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011374:Progesterone / Q000494:pharmacology*; D011506:Proteins / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013629:Tamoxifen / Q000494:pharmacology; D013997:Time Factors
D006727:Hormone Antagonists; D010446:Peptide Fragments; D010455:Peptides; D011506:Proteins; D013629:Tamoxifen; D053607:Adrenomedullin; D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol