Vasodilator actions of urocortin and related peptides in the human perfused placenta in vitro

Urocortin, is a recently isolated peptide belonging to the CRH family that binds with high affinity to the CRH2 receptor. Like CRH, urocortin causes h ypotension in the rat, but its Vasoactive actions have not yet been studied in the human. We have compared the vasoactive properties of urocortin, CRH , and urotensin-1 in the human fetal placental vasculature in vitro. Single placental lobules were bilaterally perfused (maternal and fetal sides, 5 m L/min each; 95% O-2-5% CO2; 37 C), and changes in fetal arterial perfusion pressure were recorded. Submaximal vasoconstriction was induced by PGF(2 al pha) (4 +/- 0.7 mu mol/L), which increased perfusion pressure from 19.6 +/- 1.4 to 100.7 +/- 3.1 mm Hg (n = 38; P < 0.001). Subsequent fetal arterial infusion of urocortin (0.001-1 nmol/L) caused concentration-dependent vasod ilatation. Urocortin was equipotent with urotensin-1 and 25 times more pote nt than CRH in causing vasodilatation. Nevertheless, the maximum vasodilato r responses to each of the peptides mere similar (P > 0.05). The CRH recept or antagonist, alpha-helical CRH-(9-41) (0.2 nmol/L) significantly attenuat ed the vasodilatation produced by urocortin, urotensin-1, and CRH (P < 0.05 ). These results indicate a possible physiological role for urocortin in th e modulation of human fetal placental vascular tone by activation of CRH2-l ike receptors.