Parathyroid hormone (PTH), parathyroid hormone-related peptida (PTHrp) and calcitonin gene-related peptide (CGRP) are vasodilators in various human tissues and have been localized in the uteroplacental complex. We have determined the vasoactlve effects of PTH, PTHrp and CGRP in the isolated perfused cotyledon from normotensive term human placentae. In each experiment the fetal-placental circulation was preconstricted with a constant infusion of thromboxane mimetic U46619 (lO-ZM). Increasing concentrations of PTH (lO'a-lOeM, n=5), PTHrp (10l~ n=4) or CGRP (101~ n=6) were then infused in a cumulative fashion and changes with perfusion pressure recorded. All three peptides gave a concentration-dependent vasodilator effect (p=O.O02, p=0.015, p=O.O02 for PTH, PTHrp and CGRP respectively, one way ANOVA). Perfusion pressure was reduced by approximately 50% at the highest concentration of each poptide. PTHrp and CGRP were oquipotent, but approximately 100 times more potent than PTH. The CGRP receptor-1 antagonist CGRP~7 (106M) only partially antagonized (70%) the effect of CGRP suggesting a second receptor subtype may also mediate CGRP-induced vasodilation. The nitric oxide synthase inhibitor n-nitro L-arginine (104M) did not affect the response to CGRP suggesting nitric oxide does not mediate the effect of CGRP. We conclude that the peptides PTH, PTHrp and CGRP may therefore act as vasodilators in the human fetal-placental circulation. (1993), Vol 14