Document Detail

A role for xanthine oxidase in the control of fetal cardiovascular function in late gestation sheep.
MedLine Citation:
PMID:  22331413     Owner:  NLM     Status:  MEDLINE    
Virtually nothing is known about the effects on fetal physiology of xanthine oxidase inhibition. This is despite maternal treatment with the xanthine oxidase inhibitor allopurinol being considered in human complicated pregnancy to protect the infant’s brain from excessive generation of ROS.We investigated the in vivo effects of maternal treatment with allopurinol on fetal cardiovascular function in ovine pregnancy in late gestation. Under anaesthesia, pregnant ewes and their singleton fetus were instrumented with vascular catheters and flow probes around an umbilical and a fetal femoral artery at 118±1 dGA (days of gestational age; termca. 145 days). Five days later, mothers were infused I.V. with either vehicle (n =11) or allopurinol (n =10). Fetal cardiovascular function was stimulated with increasing bolus doses of phenylephrine (PE) following maternal vehicle or allopurinol. The effects of maternal allopurinol on maternal and fetal cardiovascular function were also investigated following fetal NO blockade (n =6) or fetal β1-adrenergic antagonism (n =7). Maternal allopurinol led to significant increases in fetal heart rate, umbilical blood flow and umbilical vascular conductance, effects abolished by fetal β1-adrenergic antagonism but not by fetal NO blockade. Maternal allopurinol impaired fetal α1-adrenergic pressor and femoral vasopressor responses and enhanced the gain of the fetal cardiac baroreflex. These effects of maternal allopurinol were restored to control levels during fetal NO blockade. Maternal treatment with allopurinol induced maternal hypotension, tachycardia and acid–base disturbance. We conclude that maternal treatment with allopurinol alters in vivo maternal, umbilical and fetal vascular function via mechanisms involving NO and β1-adrenergic stimulation. The evidence suggests that the use of allopurinol in clinical practice should be approached with caution.
E A Herrera; A D Kane; J A Hansell; A S Thakor; B J Allison; Y Niu; D A Giussani
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-02-13
Journal Detail:
Title:  The Journal of physiology     Volume:  590     ISSN:  1469-7793     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-25     Completed Date:  2012-11-07     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1825-37     Citation Subset:  IM    
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MeSH Terms
Adrenergic beta-1 Receptor Antagonists / pharmacology
Allopurinol / pharmacology
Cardiovascular Physiological Phenomena / drug effects
Cardiovascular System / drug effects,  embryology*,  enzymology*
Fetus / drug effects,  enzymology
Gestational Age
Heart Rate, Fetal / drug effects
Nitric Oxide / antagonists & inhibitors
Pregnancy Complications / drug therapy,  metabolism
Regional Blood Flow / drug effects
Uric Acid / blood
Xanthine Oxidase / antagonists & inhibitors,  metabolism*
Grant Support
RG/06/006/22028//British Heart Foundation; //Biotechnology and Biological Sciences Research Council; //British Heart Foundation
Reg. No./Substance:
0/Adrenergic beta-1 Receptor Antagonists; 268B43MJ25/Uric Acid; 31C4KY9ESH/Nitric Oxide; 63CZ7GJN5I/Allopurinol; EC Oxidase
Comment In:
J Physiol. 2012 Apr 15;590(Pt 8):1773   [PMID:  22532642 ]

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