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Haemodynamic responses to an angiotensin II receptor antagonist (GR 117289) in maternal and fetal sheep
Author(s) -
Forhead AJ,
Fowden AL,
Silver M,
Hughes P,
BroughtonPipkin F,
Sutherland MF
Publication year - 1995
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.1995.sp003848
Subject(s) - fetus , blood pressure , hemodynamics , angiotensin ii , endocrinology , medicine , blood flow , bolus (digestion) , anesthesia , chemistry , pregnancy , biology , genetics
An AT1‐specific angiotensin II receptor antagonist (GR117289; 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 < 0.05; 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 mumol/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 < 0.01; 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 GR117289‐treated ewes. There were no significant differences in gestational length or neonatal outcome between vehicle‐ and GR117289‐treated groups of ewes with single fetuses.