Document Detail

Redox modulation of the fetal cardiovascular defence to hypoxaemia.
MedLine Citation:
PMID:  20807788     Owner:  NLM     Status:  MEDLINE    
Episodes of hypoxia in utero present a potentially serious challenge to the fetus, but are counteracted by defence responses including marked redistribution of blood flow from peripheral circulations to the brain. Here, we report the novel observation that the oxidant tone is an important modulator of this cardiovascular defence. Using pregnant Welsh Mountain sheep surgically prepared for long-term recording, we investigated in vivo the effects on the fetal cardiovascular defence to acute hypoxaemia of fetal treatment with the antioxidant vitamin C. The mechanisms via which vitamin C may affect the vascular oxidant tone were investigated by monitoring fetal plasma concentrations of nitrates and nitrites, by determining changes in the activity of superoxide dismutase (SOD) in fetal plasma, and by investigating the effect of vitamin C treatment on the fetal cardiovascular defence to hypoxaemia following nitric oxide (NO) synthase blockade. Fetal treatment with vitamin C markedly depressed the normal femoral constrictor response to acute hypoxaemia in the fetus (5.2 ± 1.0 vs. 1.1 ± 0.3 mmHg (ml min(-1))(-1), mean ± s.e.m.; P < 0.05) an effect which was completely restored following NO synthase blockade (6.2 ± 1.3 mmHg (ml min(-1))(-1)). Compared to saline infusion, fetal treatment with vitamin C during acute hypoxaemia also significantly increased fetal plasma SOD activity from normoxic baseline (-8.9 ± 6.5 vs. 15.0 ± 6.6% inhibition, P < 0.05) and decreased the plasma concentration ratio of nitrate:nitrite from normoxic baseline (ΔNO3(-):NO2(-); 0.15 ± 0.30 vs. -0.29 ± 0.11, P < 0.05). The data provide in vivo evidence of redox modulation of redistribution of blood flow in the fetus, part of the fetal brain sparing during acute hypoxaemic stress.
A S Thakor; H G Richter; A D Kane; C Dunster; F J Kelly; L Poston; D A Giussani
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of physiology     Volume:  588     ISSN:  1469-7793     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-09     Completed Date:  2011-03-10     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  4235-47     Citation Subset:  IM    
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MeSH Terms
Anoxia / drug therapy,  metabolism,  physiopathology*
Antioxidants / therapeutic use
Ascorbic Acid / blood,  therapeutic use
Blood Gas Analysis
Cardiovascular System / physiopathology*
Fetus / physiology*
Models, Animal
Nitrates / metabolism
Nitric Oxide / metabolism
Nitrites / metabolism
Superoxide Dismutase / metabolism
Grant Support
RG/06/006/22028//British Heart Foundation; //Biotechnology and Biological Sciences Research Council; //British Heart Foundation
Reg. No./Substance:
0/Antioxidants; 0/Nitrates; 0/Nitrites; 31C4KY9ESH/Nitric Oxide; EC Dismutase; PQ6CK8PD0R/Ascorbic Acid

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