Effects of Nitrovasodilators on the Human Fetal–Placental Circulation In Vitro

Abstract

This study examines the vasorelaxation of isolated human placental chorionic plate arteries and the perfused fetal-placental vasculature, in vitro, to a variety of nitrovasodilator compounds including glyceryl trinitrate (GTN) sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP), S-nitroso-N-glutathione (SNG) and NaNO2. The effects of these compounds were also examined under conditions of high (>450mmHg) and low oxygen (<50mmHg) tension. In a separate series of experiments the effects of GTN and NaNO2were further investigated with addition of the antioxidants cysteine (100μm), glutathione (100μm) or superoxide dismutase (SOD) (30I.U./ml). The order of nitrovasodilator potency, when added directly to isolated fetal vessels was GTN=SNP>SNAP=SNG>NaNO2. The order under low oxygen tension was similar, GTN=SNP>SNG= SNAP≥NaNO2. SNG (∼fourfold) and NaNO2(∼50-fold) were significantly more potent under low oxygen conditions. Cysteine, glutathione and SOD were without effect on GTN induced vasodilatation. However, all three agents significantly enhanced (six- to ninefold) the effects of NaNO2under similar conditions. When infused directly into the fetal–placental circulation during in vitro perfusion experiments the order of potency was GTN>SNP≥SNG≥SNAP≥NaNO2. When the nitrovasodilators were infused indirectly via the maternal intervillous space the order of potency was GTN≥SNP≥NaNO2≥SNAP=SNG. Our observations suggest that there are important differences in the action of different classes of nitrovasodilator compounds on the fetal–placental circulation. The changes observed with SNG and NaNO2may be influenced by levels of tissue oxygenation.