Vascular effects of PTHrP (1-34) and PTH (1-34) in the human fetal-placental circulation.
The aim of this study was to examine the vasodilatory effects of parathyroid hormone-related protein (PTHrP) (1-34) and parathyroid hormone (PTH) (1-34) on the human fetal-placental circulation utilising an in vitro placental perfusion model. In all experiments, the vasculature of an isolated human placental cotyledon was pre-constricted with the thromboxane A2 mimetic U46619. A simple dose of PTHrP (1-34) or PTH (1-34) (1.7-300 nM) was then infused into the fetal-placental circulation of the cotyledon. In other experiments, cotyledons were repeatedly infused with PTHrP (1-34) or PTH (1-34) (51.3 nM). Vasodilatory responses were significantly reduced in response to repeated exposure to PTHrP (1-34) (P < 0.001), indicating that this peptide desensitizes the fetal-placental vasculature. PTHrP (1-34) and PTH (1-34) equipotently stimulated a significant vasodilation of the fetal-placental circulation (P < 0.0001). The PTHrP receptor antagonist [Asn10, Leu 11]PTHrP (7-34) (102 nM) was infused in U46619-constricted placentae in the presence and absence of PTHrP (1-34) (10.2 nM). The PTHrP antagonist alone had no significant effect in the fetal-placental circulation. The antagonist significantly attenuated the response to PTHrP (1-34) (P < 0.015). Based on the data obtained in this study it is suggested that locally produced PTHrP (1-34) may be involved in the regulation of normal human fetal-placental vascular tone in autocrine and/or paracrine fashion.
Macgill
K
K
Department of Perinatal Medicine, Royal Women's Institute of Medical Research, Fitzroy, Victoria, Australia.
Moseley
J M
JM
Martin
T J
TJ
Brennecke
S P
SP
Rice
G E
GE
Wlodek
M E
ME
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D005260:Female; D005333:Fetus / Q000098:blood supply*; D006801:Humans; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D010920:Placenta / Q000098:blood supply* / Q000187:drug effects; D011247:Pregnancy; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011506:Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone / Q000037:antagonists & inhibitors; D019379:Teriparatide / Q000008:administration & dosage / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011450:Prostaglandin Endoperoxides, Synthetic; D011506:Proteins; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone; D014662:Vasoconstrictor Agents; D019379:Teriparatide; C054296:parathyroid hormone-related protein (1-34); D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid