SELECTIVE VASODILATOR EFFECTS OF ATRIAL-NATRIURETIC-PEPTIDE IN THE HUMAN PLACENTAL VASCULATURE

OBJECTIVE: To determine whether atrial natriuretic peptide (ANP) atten uates the vasoconstrictor effects of angiotensin II (AII), a thromboxa ne mimetic (U46619), and endothelin-1 in the human fetal-placental vas culature and to determine whether nitric oxide (NO) has a role in the vasodilator activity of ANP. METHODS: Isolated placental cotyledons we re dually perfused, with fetal perfusion pressure used as an index of vascular response. The effects of AII (10-(10)-10-(6) mol/L bolus inje ction), endothelin-1 (10(-7) mol/L bolus), and U46619 (10(-9)-10(-6) m ol/L bolus or 10(-8) mol/L infusion) were established in the absence o r presence of ANP (10(-8) mol/L). The role of NO as a mediator of ANP action was investigated by perfusion with n-nitro-L-arginine (NNLA, 10 (-3) mol/L), an inhibitor of NO synthase. Statistical significance was determined by analysis of variance. RESULTS: Atrial natriuretic pepti de caused significant attenuation of vasoconstrictor responses to AII, but weak attenuation of endothelin-1 and no attenuation of U46619. Us e of NNLA did not affect the attenuation of AII-induced vasoconstricti on by ANP. CONCLUSION: Atrial natriuretic peptide is a vasodilator of the fetal-placental vasculature constricted with AII and endothelin-1, but not with U46619. Nitric oxide does not mediate the action of ANP.