Infusion of pregnant rats with calcitonin gene-related peptide (CGRP)(8-37), a CGRP receptor antagonist, increases blood pressure and fetal mortality and decreases fetal growth.
Calcitonin gene-related peptide (CGRP) is the most potent endogenous vasodilatory peptide, and is involved in the regulation of blood flow to vital organs. We have previously shown that CGRP may be involved in vascular adaptations that occur during pregnancy, and that steroid hormones may be involved in these mechanisms. We hypothesized that endogenous CGRP is required for maintaining blood pressure and fetoplacental growth in pregnant rats, and that progesterone will enhance CGRP effects. The vasodilatory effects of CGRP are known to be inhibited by a competitive CGRP receptor antagonist, the C-terminal fragment CGRP(8-37). In the present study, we investigated whether continuous s.c. infusion of CGRP(8-37) to pregnant rats will reduce fetoplacental growth and increase systolic blood pressure. We also assessed whether progesterone will alter the effects of CGRP(8-37) on blood pressure during postpartum. Groups of five pregnant rats were s.c. infused with varying doses of CGRP(8-37) from Day 17 of pregnancy. Daily systolic blood pressures, pup weight, mortality at term delivery, and fetoplacental weights on Day 20 of gestation were measured. CGRP(8-37) at a dose of 0.083 mg day(-1) kg(-1) body weight (BW) showed no effects; however, doses of 0.33 and 1.33 mg day(-1) kg(-1) BW increased (P < 0.05) blood pressure during pregnancy, and these elevated blood pressures persisted during postpartum with the highest dose used. Progesterone (2 mg per injection, twice a day; s.c.) treatment significantly elevated blood pressure in rats infused with CGRP(8-37) during postpartum, suggesting that progesterone regulates CGRP-induced vascular effects. CGRP(8-37) infusion caused significant reductions in pup weight with an increase in mortality rate, and these effects were dose-dependent. Placental and fetal weights were also decreased prior to term on Day 20 of gestation, 72 h after CGRP(8-37) infusion, indicating effects on uteroplacental tissues. Therefore, we suggest that endogenous CGRP plays an important role in maintaining normal fetoplacental development, fetal survival, and vascular adaptations during pregnancy.
Department of Obstetrics/Gynecology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1062, USA.
P R R
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Gangula
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YL
Dong
S J
SJ
Wimalawansa
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C
Yallampalli
D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005313:Fetal Death / Q000139:chemically induced*; D020567:Fetal Weight / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D010920:Placenta / Q000098:blood supply / Q000187:drug effects; D010929:Placentation; D049590:Postpartum Period / Q000502:physiology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011374:Progesterone / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D011374:Progesterone; D015740:Calcitonin Gene-Related Peptide