Journal of Clinical Endocrinology & Metabolism, Vol 80, 2888-2893, Copyright © 1995 by Endocrine Society

ARTICLES

Corticotropin-releasing hormone-induced vasodilatation in the human fetal-placental circulation: involvement of the nitric oxide-cyclic guanosine 3',5'-monophosphate-mediated pathway

VL Clifton, MA Read, IM Leitch, WB Giles, AL Boura, PJ Robinson and R Smith
Maternal Health Research Center, John Hunter Hospital, Newcastle, New South Wales, Australia.

This study has used an in vitro perfusion method to investigate the mechanism by which CRH causes vasodilatation in the human fetal- placental circulation. In normal term placentas, vasodilatory responses to human CRH (24-7000 pmol/L) were examined during submaximal vasoconstriction (100-120 mm Hg) of the fetal-placental vasculature induced by prostaglandin F2 alpha (0.7-2 mumol/L), KCl (50-100 mmol/L), or the thromboxane A2 mimetic, U46619 (0.05-0.5 mumol/L). Infusion of CRH caused a concentration-dependent vasodilatation that was similar in the presence of each constrictor agent (P > 0.05). The CRH antagonist, alpha-helical CRH-(9-41) (200 pmol/L), and a polyclonal CRH antiserum significantly inhibited CRH-induced vasodilatation during constriction with prostaglandin F2 alpha (P < 0.05). Vasodilatory responses to CRH were attenuated by the nitric oxide synthase inhibitor, N omega-nitro-L- arginine (100 mumol/L; P < 0.05), and the guanylate cyclase inhibitor, LY 83583 (1 mumol/L; P < 0.05), but not by the cyclooxygenase inhibitor, indomethacin (3 mumol/L; P > 0.05). In placentas of women with increased fetal vascular resistance, as demonstrated by Doppler ultrasound waveforms in vivo, CRH-induced vasodilatation was significantly reduced (P < 0.05). These results indicate that in the human fetal-placental circulation, CRH causes a vasodilatory response via a nitric oxide-/cGMP-dependent pathway. CRH may play a role in the control of vascular resistance to blood flow in the normal human placenta, and there may be a deficiency in the CRH signaling pathway of placentas with increased fetal vascular resistance.

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