Placent~r (1992), 13, 595-605 Evidence for Inhibition by Endothelium- Derived Relaxing Factor of Thromboxane A2 Receptor-Mediated Vasoconstriction in the Fetal Vessels of the Human Perfused Placenta N. M. GUDE”, A. L. A. BOURAb, R. G. KING”, S. P. BRENNECKEO, 0. S. JAMALb, R. SMITHb & W. A. W. WALTERSb,“ ”,Uonash Perimtal Ikit of the Department of Obstetrics and Gynecology and the Dtpartmnt qfPharmacology, Monash Uniter- si(y, ~tlelboarne I’Disciplines of Reproducti~~e .lledicine and Medicine, Uniwrsi<~~ ~1 .\emastle, iVemcastle. .4ustralia. ’To mhom correspondence should be addressed at: Discipline uf Reproductive Medick, C’nirersi~yof .Vevelocastle9 Shortland, ,\SR ; 2308, Australia SUMMARY Three inhibitors of the release or eflects of endothelium-derived relaxing factor (EDRbJ, :V-nitro-L-arginine, methylene blue and oxyhemoglobin, caused further increases in perfusion pressure during vascular constriction with submaximal concen- trations of the thromboxaneA2-mimetic, U46619 in fetal vessels of human placental lobules perfiused in vitro. The results suggest the EDRF, released during constriction of fetal placental vessels in response to thromboxane,42 receptor stimulation, attenuates the vasoconstrictor response. Hence, impairment of EDRF release or function could contribute to the reduced placental blood jaw obsenled in various disease states associated mith increased thromboxane AZ production such as pre-eclampsia. INTRODUCTION The control of resistance offered to blood flow by the fetal vasculature of the human placenta is not completely understood. However, locally generated and circulating autacoids are generally accepted to make important contributions (for review see Boura and Walters, 1991) since nerves are not present in the fetal extracorporeal blood vessels (Fox and Khong, 1990). It is also known that some placental insufficiency states are associated with increased 0143-4004/92/060597 + 09 $08.00/O 0 1992 Baillike Tindall Ltd