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Submitted on September 15, 2004
Accepted on February 4, 2005
Maternal & Fetal Health Research Centre, The University of Manchester, St. Mary's Hospital, Manchester, U.K.
* To whom correspondence should be addressed. E-mail: mark.wareing{at}man.ac.uk.
Background: Fetal growth restriction (FGR) affects up to 8% of all pregnancies and has massive short-term (increased fetal morbidity and mortality) and long-term (increased incidence of cardiovascular disease in adulthood) health implications. Doppler waveform analysis of pregnancies complicated by FGR suggests compromised uteroplacental circulation and placental hypoperfusion. Our aim was to determine whether myometrial small artery function was aberrant in FGR, and to assess if sildenafil citrate could improve vasodilatation in FGR pregnancies.
Methods: Small arteries dissected from myometrial biopsies obtained at Caesarean section from normal pregnant (n = 27) or women whose pregnancies were complicated by FGR (n = 12) were mounted on wire myographs. Vessels were constricted (with arginine vasopressin or U46619) and relaxed (with bradykinin) pre- and post-incubation with a phosphodiesterase-5 inhibitor, sildenafil citrate.
Results: We demonstrated increased myometrial small artery vasoconstriction and decreased endothelium-dependent vasodilatation in vessels from women whose pregnancies were complicated by FGR. Sildenafil citrate significantly reduced vasoconstriction and significantly improved relaxation of FGR small arteries.
Conclusions: We conclude that sildenafil citrate improves endothelial function of myometrial vessels from women whose pregnancies are complicated by intrauterine growth restriction. Sildenafil citrate may offer a potential therapeutic strategy to improve uteroplacental blood flow in FGR pregnancies.
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