VASCULAR-RESPONSES TO SODIUM-NITROPRUSSIDE IN THE HUMAN FETAL-PLACENTAL CIRCULATION

This study examined the activity of sodium nitroprusside (SNP) in the human fetal-placental circulation in vitro in pathological and experim ental conditions in which vascular function may be impaired. SNP (13-3 400 nM) caused a concentration-dependent reduction in fetal arterial p erfusion pressure (FAP) in Krebs' perfused placental coty]edons, at ba sal tone and following pre-constriction with prostaglandin F-2 alpha ( PGF(2 alpha)). SNP-induced reduction in FAP in the PGF(2 alpha) pre-co nstricted fetal-placental circulation was enhanced approximately six-f old (5.85) in those placentae pre-treated with the nitric oxide (NO) s ynthase inhibitor N-omega-nitro-L-arginine (100 mu M). Reductions in F AP in the preconstricted fetal-placental vasculature caused by SNP wer e not altered by prior infusion of ouabain (100 nM) into the fetal cir culation or during low oxygen perfusion (O-2 tension <50 mmHg). No dif ferences were observed in the responses obtained to SNP in placentae o btained from women with normotensive pregnancies or those associated w ith (i) pregnancy-induced hypertension, (ii) intra-uterine growth reta rdation, or (iii) an elevated umbilical-artery Doppler-ultrasound syst olic/diastolic ratio, in either preconstricted placentae or those at b asal tone. These findings are consistent with an up-regulation of guan ylate cyclase/cGMP-mediated vasodilatation in the fetal-placental vasc ulature following complete blockade of endogenous NO production.