HEMODYNAMIC-RESPONSES TO AN ANGIOTENSIN-II RECEPTOR ANTAGONIST (GR117289) IN MATERNAL AND FETAL SHEEP

An AT(1)-specific angiotensin II receptor antagonist (GR117289; 1 mg/k g i.v. bolus) was administered daily to ten chronically catheterized, normotensive ewes during late pregnancy (from 126 +/- 1 days) until pa rturition (139 +/- 1 days); five control animals received an equivalen t volume of vehicle solution. Following drug administration, mean mate rnal blood pressure decreased from 87 +/- 1 mmHg to a minimum of 79 +/ - 1 mmHg at 0.5 h (P < 0.05; n = 10) and remained low for 4-6 h withou t any concomitant change in fetal blood pressure or maternal and fetal heart rates. In animals fitted with flow probes, uterine blood flow d ecreased from 443 +/- 21 to 363 +/- 27 ml/min at 0.5 h post-drug (P < 0.05; n = 6); this change-was positively correlated with the reduction in maternal blood pressure. The mean decrements in uterine and umbili cal blood flows measured by steady-state infusion of tritiated water w ere -611 +/- 171 ml/min at 4-6 h (P < 0.05; n = 5) and -71 +/- 19 ml/m in at 0.5-1 h (P < 0.05; n = 5), respectively. Significant reductions (P < 0.05; n = 10) in fetal arterial oxygen tension (-1.6 +/- 0.4 mmHg ), saturation (-6.6 +/- 1.6 %) and content (-0.3 +/- 0.1 mu mol/ml) we re evident at 0.5 h post-drug and were maintained for 6-12 h. Umbilica l oxygen delivery decreased at 0.5-1 h following drug administration ( P < 0.01; n = 5), but was unaccompanied by any significant change in f etal oxygen consumption. Chronic decreases in daily fetal pH and blood oxygen content occurred in GR117289-treated ewes. There were no signi ficant differences in gestational length or neonatal outcome between v ehicle- and GR117289-treated groups of ewes with single fetuses.