Effects of nitrovasodilators on the human fetal-placental circulation in vitro

This study examines the vasorelaxation of isolated human placental chorioni c 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-nit roso-N-glutathione (SNG) and NaNO2. The effects of these compounds were als o examined under conditions of high (> 450 mmHg) and low oxygen (< 50 mmHg) tension. In a separate series of experiments the effects of GTN and NaNO2 were further investigated with addition of the antioxidants cysteine (100 m um), glutathione (100 mum) or superoxide dismutase (SOD) (30 I.U./ml). The order under low oxygen tension was similar, GTN=SNP > SNG=SNAP greater than or equal to NaNO2. SNG (similar to fourfold) and NaNO2 (similar to 50-fold ) were significantly more potent under low oxygen conditions. Cysteine, glu tathione and SOD were without effect on GTN induced vasodilation. However, all three agents significantly enhanced (six- to ninefold) the effect of Na NO2 under similar conditions. When infused directly into the fetal-placenta l circulation during in vitro perfusion experiments the order of potency wa s GTN > SNP greater than or equal to SNG greater than or equal to SNAP grea ter than or equal to NaNO2. When the nitrovasodilators were infused indirec tly via the maternal intervillous space the order of potency was GTN greate r than or equal to SNP greater than or equal to NaNO(2)greater than or equa l to SNAP=SNG. Out observations suggest that there are important difference s in the action of different classes of nitrovasodilator compounds on the f etal-placental circulation. The changes observed with SNG and NaNO2 may be influenced by levels of tissue oxygenation. (C) 2001 Harcourt Publishers Lt d.