1 The effects of antagonism of the maternal renin-angiotensin system (RAS) with either an angiotensin II type 1-(ATI) specific receptor blocker (GR138950) or an angiotensin-converting enzyme (ACE) inhibitor (captopril) 9 The present study demonstrated that administration of either GR138950 or captopril to pregnant ewes effectively blocked the maternal RAS, and caused hypotension and a decrease in uterine blood flow. However, only captopril appeared to cross the placenta to influence directly the RAS of the sheep foetus. This suggests that the fall in foetal oxygenation observed after AT,-specific receptor blockade and ACE inhibition originates primarily from changes in the maternal and/or placental vasculature. Despite these changes, neither GR138950 nor captopril were detrimental to the outcome of pregnancy when foetal blood loss was kept to a minimum.
SUMMARYAn ATI-specific angiotensin II receptor antagonist (GRI 17289; 1 mg/kg I.v. bolus) was administered daily to ten chronically catheterized, normotensive ewes during late pregnancy (from 126 ± 1 days) until parturition (139 + 1 days); five control animals received an equivalent volume of vehicle solution. Following drug administration, mean maternal blood pressure decreased from 87 ± 1 mmHg to a minimum of 79 ± 1 mmHg at 0 5 h (P < 005; n = 10) and remained low for 4-6 h without any concomitant change in fetal blood pressure or maternal and fetal heart rates. In animals fitted with flow probes, uterine blood flow decreased 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 umbilical blood flows measured by steady-state infusion of tritiated water were -611 ± 171 ml/min at 4-6 h (P < 0 05; n = 5) and -71 + 19 ml/min 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 4umol/ml) were evident at 0.5 h post-drug and were maintained for 6-12 h. Umbilical oxygen delivery decreased at 0 5-1 h following drug administration (P <001; n = 5), but was unaccompanied by any significant change in fetal oxygen consumption. Chronic decreases in daily fetal pH and blood oxygen content occurred in GRl 17289-treated ewes. There were no significant differences in gestational length or neonatal outcome between vehicle-and GRI 17289-treated groups of ewes with single fetuses.
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