Document Detail

Statin treatment depresses the fetal defence to acute hypoxia via increasing nitric oxide bioavailability.
MedLine Citation:
PMID:  22106179     Owner:  NLM     Status:  MEDLINE    
In addition to lowering cholesterol, statins increase nitric oxide (NO) bioavailability, improving endothelial function. In the fetus, enhanced NO during acute hypoxia opposes the fetal peripheral vasoconstrictor response, part of the brain-sparing defence. This study tested the hypothesis that treatment with statins depresses the fetal circulatory response to acute hypoxic stress via increasing NO bioavailability. Under anaesthesia, 12 fetal sheep at 118 ± 1 days of gestation (term ca 145 days) were instrumented with vascular catheters and a femoral artery Transonic flow probe for chronic recording. Five days later, all animals were subjected to 30 min of acute hypoxia (fetal arterial partial pressure of O(2) ( ) reduced by ca 50%) before and 24 h after fetal treatment with pravastatin (25 mg i.v.). In half of the fetuses (n = 6), responses to hypoxia post-pravastatin were evaluated during NO synthesis blockade. Fetal exposure to pravastatin did not affect fetal basal cardiovascular function. Fetal was similarly reduced in all acute hypoxia experiments from ca 21 to 10 mmHg. Fetal exposure to pravastatin markedly diminished the fetal femoral vasoconstrictor (5.1 ± 0.9 vs. 2.5 ± 0.5 mmHg (ml min(-1))(-1)) and lactic acidaemic (4.4 ± 0.5 vs. 3.0 ± 0.3 mm) responses to acute hypoxia (both P < 0.05), without affecting plasma catecholamine responses. Post-pravastatin, the circulatory (5.8 ± 1.5 mmHg (ml min(-1))(-1)) and metabolic (3.9 ± 0.3 mm) responses could be restored to control levels during fetal treatment with NO synthase blockade. Pravastatin depresses the fetal cardiovascular and metabolic defences to acute hypoxia via increasing NO bioavailability. The use of statins during pregnancy should be viewed with extreme caution.
Andrew D Kane; Emilio A Herrera; Jeremy A Hansell; Dino A Giussani
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-11-21
Journal Detail:
Title:  The Journal of physiology     Volume:  590     ISSN:  1469-7793     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-16     Completed Date:  2012-06-20     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  323-34     Citation Subset:  IM    
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MeSH Terms
Anoxia / physiopathology*
Anticholesteremic Agents / pharmacology*
Biological Availability
Blood Gas Analysis
Cardiovascular System / drug effects,  embryology,  physiopathology
Catecholamines / blood
Endocrine System / drug effects,  embryology,  physiopathology
Fetus / drug effects*,  physiology*
Models, Animal
Nitric Oxide / metabolism*
Nitric Oxide Synthase / antagonists & inhibitors
Pravastatin / pharmacology*
Vasomotor System / drug effects,  embryology,  physiopathology
Grant Support
RG/06/006/22028//British Heart Foundation; //British Heart Foundation
Reg. No./Substance:
0/Anticholesteremic Agents; 0/Catecholamines; 31C4KY9ESH/Nitric Oxide; EC Oxide Synthase; KXO2KT9N0G/Pravastatin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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