Document Detail

Haemodynamic responses to an angiotensin II receptor antagonist (GR 117289) in maternal and fetal sheep.
MedLine Citation:
PMID:  7786519     Owner:  NLM     Status:  MEDLINE    
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.
A J Forhead; A L Fowden; M Silver; P Hughes; F Broughton-Pipkin; M F Sutherland
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental physiology     Volume:  80     ISSN:  0958-0670     ISO Abbreviation:  Exp. Physiol.     Publication Date:  1995 Mar 
Date Detail:
Created Date:  1995-07-24     Completed Date:  1995-07-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9002940     Medline TA:  Exp Physiol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  285-98     Citation Subset:  IM    
Physiological Laboratory, University of Cambridge, UK.
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MeSH Terms
Blood Gas Analysis
Blood Pressure / drug effects
Fetal Viability / drug effects
Fetus / blood supply,  physiology*
Gestational Age
Heart Rate / drug effects
Hemodynamics / drug effects*
Injections, Intravenous
Nicotinic Acids / pharmacology*
Receptors, Angiotensin / antagonists & inhibitors*
Regional Blood Flow / physiology
Sheep / embryology,  physiology*
Tetrazoles / pharmacology*
Uterus / blood supply
Reg. No./Substance:
0/Nicotinic Acids; 0/Receptors, Angiotensin; 0/Tetrazoles; 145781-32-4/GR 117289

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