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Vasodilator Actions of Urocortin and Related Peptides in the Human Perfused Placenta in Vitro¹

Discipline of Reproductive Medicine (I.M.L., A.L.A.B., C.B., W.A.W.W.), Division of Obstetrics and Gynecology (M.A.R.), and Endocrine Unit (R.S.), Mothers and Babies Research Center, University of Newcastle, John Hunter Hospital, Newcastle, New South Wales 2310, Australia

Address all correspondence and requests for reprints to: Dr. Ian M. Leitch, at present address: Miravant Pharmaceuticals Inc., 7408 Hollister Avenue, Santa Barbara, California 93117. E-mail: Ileitch{at}miravant.com

Urocortin, is a recently isolated peptide belonging to the CRH family that binds with high affinity to the CRH₂ receptor. Like CRH, urocortin causes hypotension 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 mL/min each; 95% O₂-5% CO₂; 37 C), and changes in fetal arterial perfusion pressure were recorded. Submaximal vasoconstriction was induced by PGF₂ (4 ± 0.7 µmol/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 vasodilatation. Urocortin was equipotent with urotensin-1 and 25 times more potent than CRH in causing vasodilatation. Nevertheless, the maximum vasodilator responses to each of the peptides were similar (P > 0.05). The CRH receptor antagonist, -helical CRH-(9–41) (0.2 nmol/L) significantly attenuated the vasodilatation produced by urocortin, urotensin-1, and CRH (P < 0.05). These results indicate a possible physiological role for urocortin in the modulation of human fetal placental vascular tone by activation of CRH₂-like receptors.

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