Document Detail

Sildenafil citrate rescues fetal growth in the catechol-O-methyl transferase knockout mouse model.
MedLine Citation:
PMID:  22392899     Owner:  NLM     Status:  MEDLINE    
Preeclampsia and fetal growth restriction are responsible for the majority of maternal and perinatal morbidity and mortality associated with complicated pregnancies. Although their etiologies are complex and multifactorial, both are associated with increased uterine artery resistance. Sildenafil citrate is able to rescue the dysfunction observed ex vivo in uterine arteries of women with preeclampsia. The ability of sildenafil citrate to increase uterine artery vasodilation, thereby decreasing uterine artery resistance and, hence, ameliorated preeclampsia and fetal growth restriction, was tested in a mouse model of preeclampsia, the catechol-O-methyl transferase knockout mouse (COMT(-/-)). COMT(-/-) and C57BL/6J mice were treated (0.2 mg/mL in drinking water, n=6-12) from gestational day 12.5 to 18.5. Measures of pup growth, including body weight, crown/rump length, and abdominal circumference, were reduced in COMT(-/-) mice; this was normalized after treatment with Sildenafil. COMT(-/-) mice also demonstrated abnormal umbilical Doppler waveforms, including reverse arterial blood flow velocity. This was normalized after treatment with Sildenafil. Abnormal uterine artery Doppler waveforms were not demonstrated in COMT(-/-) mice, although ex vivo responses of uterine arteries to phenylephrine were increased; moreover, treatment with Sildenafil did improve ex vivo sensitivity to an endothelium-dependent vasodilator. The data presented here demonstrate that Sildenafil can rescue pup growth and improve abnormal umbilical Doppler waveforms, providing support for a potential new therapeutic strategy targeting fetal growth restriction.
Joanna L Stanley; Irene J Andersson; Rajan Poudel; Christian F Rueda-Clausen; Colin P Sibley; Sandra T Davidge; Philip N Baker
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-03-05
Journal Detail:
Title:  Hypertension     Volume:  59     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-20     Completed Date:  2012-06-14     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1021-8     Citation Subset:  IM    
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MeSH Terms
Blood Flow Velocity / drug effects
Catechol O-Methyltransferase / metabolism*
Disease Models, Animal
Fetal Growth Retardation / physiopathology*,  prevention & control*,  ultrasonography
Hypertension / complications,  diagnosis
Mice, Inbred C57BL
Mice, Knockout
Myometrium / blood supply*
Piperazines / administration & dosage*
Pre-Eclampsia / drug therapy*,  physiopathology
Proteinuria / complications,  diagnosis
Purines / administration & dosage
Sulfones / administration & dosage*
Ultrasonography, Doppler
Umbilical Arteries / drug effects*,  ultrasonography
Vasodilation / drug effects
Vasodilator Agents / administration & dosage
Grant Support
G0802770//Medical Research Council; //Medical Research Council
Reg. No./Substance:
0/Piperazines; 0/Purines; 0/Sulfones; 0/Vasodilator Agents; 3M7OB98Y7H/sildenafil; EC O-Methyltransferase

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

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