Adrenocorticotropin causes vasodilatation in the human fetal-placental circulation

During human pregnancy, ACTH is produced by both the placenta and fetal pituitary ACTH has been shown to cause vasodilatation in the adrenal cortex in, vitro. In this context we have investigated the vasoactive effects of ACTH in the human fetal-placental circulation. Single lobules of term human placentas were bilaterally perfused in vitro with Krebs solution (maternal and fetal, 5 mL/min; 95% O-2-5% CO2; 37 C; pH 7.3), and changes in fetal placental arterial perfusion pressure (FAP)were measured. ACTH (40-4000 pmol/L; n = 5) caused a dose-dependent reduction of both KCl and PGF(2 alpha)-induced increases in FAP in the fetal placental circulation. The reductions were of a similar magnitude in the presence of either constrictor agent. ACTH was 187.4 (95% confidence limits, 162.7-215.9) times more potent than prostacyclin (PGI(2); 1.2-1180 nmol/L; n = 6), which is a known vasodilator of the fetal-placental circulation. The threshold concentrations for ACTH and PGI(2) were 40 pmol/L and 1.2 nmol/L, respectively. ACTH-induced reductions in PGF2 alpha-induced increases in FAP in the fetal placental circulation were not inhibited by the nitric oxide synthase inhibitor, N-omega-nitro-L-arginine (100 mu mol/L; n = 5), the cyclooxygenase inhibitor indomethacin (3 mu mol/L; n = 5), or a guanylate cyclase inhibitor LY 83583 (1 mu mol/L; n = 5). The inhibitory effect of ACTH was attenuated by the antagonist, ACTH-(7-38) (240 pmol/L; n = 4), and a polyclonal ACTH antiserum (1:1000 dilution; n = 4). We have demonstrated that ACTH causes a reduction in fetal placental vascular resistance in the human fetal-placental circulation in vitro. The mechanism by which it exerts these effects has not been defined, but neither nitric oxide nor PC-mediated pathways appear to be involved.