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A role for xanthine oxidase in the control of fetal cardiovascular function in late gestation sheep
Author(s) -
Herrera E. A.,
Kane A. D.,
Hansell J. A.,
Thakor A. S.,
Allison B. J.,
Niu Y.,
Giussani D. A.
Publication year - 2012
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2011.224576
Subject(s) - allopurinol , xanthine oxidase , fetus , xanthine oxidase inhibitor , endocrinology , medicine , gestation , xanthine , pregnancy , pharmacology , biology , biochemistry , enzyme , genetics
Key points • There is growing physiological and clinical interest in the role of the enzyme xanthine oxidase in the regulation of fetal cardiovascular function. • The xanthine oxidase inhibitor allopurinol is undergoing human clinical trials in complicated pregnancy to protect the fetal brain from injury by decreasing excessive generation of reactive oxygen species (ROS) and increasing nitric oxide (NO) availability. However, the effects on fetal cardiovascular physiology of xanthine oxidase inhibition are largely unknown. • We have previously reported that the balance between ROS and NO plays an important physiological role in the control of fetal cardiovascular function. Therefore, it seems likely that allopurinol might perturb this balance and alter fetal cardiovascular homeostasis. • Here, we report that maternal allopurinol treatment in late gestation ovine pregnancy has significant in vivo effects on umbilical blood flow and the cardiovascular system of the mother and fetus by altering NO and β 1 ‐adrenergic mechanisms. • The evidence suggests that xanthine oxidase has an important role in basal cardiovascular function in the fetus during late gestation. Therefore, further research is warranted before safe clinical application of maternal allopurinol during pregnancy in humans.