EFFECT OF THE L-ARGININE NITRIC-OXIDE PATHWAY ON HUMAN PLACENTAL VASCULAR TONE AND CORTICOTROPIN-RELEASING HORMONE-SECRETION

Objective: Reduced placental output of nitric oxide (NO) may contribut e to increased vascular resistance and abnormally elevated corticotrop in-releasing hormone (CRH) levels in umbilical cord plasma in pregnanc ies complicated by pregnancy-induced hypertension. The aim of this stu dy was to investigate the effects of the NO synthase inhibitor NO-nitr o-L-arginine (L-NOARG) and the NO substrate L-arginine on placental va scular hemodynamics and CRH secretion. Methods: Single lobules of term placentae in vitro, from normal pregnant women were bilaterally perfu sed with Krebs' solution (5 mL/min, 95% O-2, 5% CO2, 37 degrees C, pH 7.3) and changes in fetal arterial pressure (FAP) recorded. Fetal and maternal perfusates were collected at 4 degrees C every 10 min for 3 h and CRH immunoreactivity in perfusates measured by radioimmunoassay. Results: Placentae used in this study, from women aged 28 +/- 6 years, had a basal FAP of 23 +/- 3 mm Hg (n = 4). Infusion of L-NOARG (100 m u M) increased placental FAP (ANOVA, P < 0.05) with no significant eff ects on outflow volumes of placental perfusates (ANOVA, P > 0.05). L-N OARG also elevated placental CRH release into fetal perfusates (ANOVA, P < 0.05). L-Arginine (100 mu M) infusion partly reduced the elevatio n in FAP (ANOVA, P > 0.05) and reversed the increase in CRH secretion caused by L-NOARG (ANOVA, P < 0.05). Conclusions: These data indicate that pharmacological blockade of human placental NO output leads to el evated fetal placental resistance and CRH release. Thus, the L-arginin e-nitric oxide system appears to play a pivotal role in modulating hum an fetal placental vascular hemodynamics and release of CRH.