| STATIN TREATMENT DEPRESSES THE FETAL DEFENCE TO ACUTE HYPOXIA VIA INCREASING NITRIC OXIDE BIOAVAILABILITY. | |
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MedLine Citation:
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PMID: 22106179 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. 145d) 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 PaO2 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 PaO2 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. |
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Authors:
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Andrew D Kane; Emilio A Herrera; Jeremy A Hansell; Dino A Giussani |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-21 |
Journal Detail:
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Title: The Journal of physiology Volume: - ISSN: 1469-7793 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-22 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0266262 Medline TA: J Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Physiology, Development and Neuroscience, University of Cambridge, UK. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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