| A role for xanthine oxidase in the control of fetal cardiovascular function in late gestation sheep. | |
| | |
MedLine Citation:
|
PMID: 22331413 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
E A Herrera; A D Kane; J A Hansell; A S Thakor; B J Allison; Y Niu; D A Giussani |
Related Documents
:
|
21102173 - A case of massive meconium peritonitis in utero successfully managed by planned cardiop... 10579163 - Fetal scarless wound healing. 1799343 - Recurrent miscarriage--outcome after supportive care in early pregnancy. |
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: 2013-04-15 |
Medline Journal Info:
|
Nlm Unique ID: 0266262 Medline TA: J Physiol Country: England |
Other Details:
|
Languages: eng Pagination: 1825-37 Citation Subset: IM |
Affiliation:
|
Department of Physiology Development & Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adrenergic beta-1 Receptor Antagonists
/
pharmacology Allopurinol / pharmacology Animals Cardiovascular Physiological Phenomena / drug effects Cardiovascular System / drug effects, embryology*, enzymology* Female Fetus / drug effects, enzymology Gestational Age Heart Rate, Fetal / drug effects Nitric Oxide / antagonists & inhibitors Pregnancy Pregnancy Complications / drug therapy, metabolism Regional Blood Flow / drug effects Sheep Uric Acid / blood Xanthine Oxidase / antagonists & inhibitors, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
|
//British Heart Foundation; //Biotechnology and Biological Sciences Research Council |
| Chemical | |
Reg. No./Substance:
|
0/Adrenergic beta-1 Receptor Antagonists; 10102-43-9/Nitric Oxide; 315-30-0/Allopurinol; 69-93-2/Uric Acid; EC 1.17.3.2/Xanthine Oxidase |
| Comments/Corrections | |
Comment In:
|
J Physiol. 2012 Apr 15;590(Pt 8):1773
[PMID:
22532642
]
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Structure-Function Analysis of the Coiled-Coil and Leucine-Rich Repeat Domains of the RPS5 Disease R...
Next Document: HCO(3)(-)-independent conductance with a mutant Na(+)/HCO(3)(-) cotransporter (SLC4A4) in a case of ...