Vasodilator effects of parathyroid hormone, parathyroid hormone-related protein, and calcitonin gene-related peptide in the human fetal-placental circulation.
OBJECTIVE
The purpose of our study was to determine the vasoactivity of calcitonin gene-related peptide (CGRP), parathyroid hormone (PTH), and parathyroid hormone-related protein (PTHrP) in the human fetal-placental circulation in vitro.


METHODS
Dually perfused placental cotyledons from term pregnancies were used in this study.


RESULTS
Calcitonin gene-related peptide, PTHrP (both 10(-10)-10(-6) mol/L), and PTH (10(-8)-10(-6) mol/L) demonstrated a significant concentration-dependent vasodilator effect (P = .0007, P = .0172, P = .0063, respectively), following preconstriction with a thromboxane mimetic U46619. The CGRP-1 receptor inhibitor CGRP8-37 (10(-6) mol/L) significantly inhibited (P = .0131) the CGRP-induced vasodilator effect, while the nitric oxide synthesis inhibitor n-nitro-l-arginine showed no inhibitory effect.


CONCLUSIONS
These results demonstrate the vasodilator effects of CGRP, PTH, and PTHrP in the human fetal-placental circulation. Calcitonin gene-related peptide and PTHrP were of equal potency, and both were approximately 100 times more potent than PTH. This study also suggests the CGRP may exert its vasodilator effect through two classes of receptors in the human placenta and may do so independently of nitric oxide.
Mandsager
N T
NT
Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, OH 45267-0526, USA.
Brewer
A S
AS
Myatt
L
L
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D005260:Female; D005333:Fetus / Q000098:blood supply*; D006801:Humans; D010281:Parathyroid Hormone / Q000502:physiology*; D044162:Parathyroid Hormone-Related Protein; D021041:Placental Circulation / Q000502:physiology*; D011247:Pregnancy; D011506:Proteins / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*
C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D014662:Vasoconstrictor Agents; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015740:Calcitonin Gene-Related Peptide