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-pla cental circulation in vitro. METHODS: Dually perfused placental cotyle dons from term pregnancies were used in this study. RESULTS: Calcitoni n gene-related peptide, PTHrP (both 10(-10)-10(-6) mol/L), and PTH (10 (-8)-10(-6) mol/L) demonstrated a significant concentrative-dependent vasodilator effect (P = .0007, P = .0172, P = .0063, respectively), fo llowing preconstriction with a thromboxane mimetic U46619. The CGRP-1 receptor inhibitor CGRP(8-37), (10(-6) mol/L) significantly inhibited (P = .0131) the CGRP-induced vasodilator effect, while the nitric oxid e 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 weve of equal potency, and both were ap proximately 100 times move patent than PTH. This study also suggests t he CGRP may exert its vasodilator effect through two classes of recept ors in the human placenta and may do so independently of nitric oxide.