Phosphodiesterase Inhibitor Effect on Small Artery Function in Preeclampsia

Samangaya, Rebekah A.; Wareing, Mark; Skillern, Laurence; Baker, Philip N.

doi:10.3109/10641955.2010.484083

Cited by 17 publications

(9 citation statements)

References 15 publications

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“…Interestingly, recent studies have shown that sildenafil can be used successfully to correct a thin endometrium and reduce recurrent implantation failure (15,16), and therapeutically for intrauterine growth restriction (IUGR) and pre-eclampsia (17,18). Others have refuted the suggested benefits of sildenafil as a treatment for preeclampsia (19,20), but the intervention might have been applied too late to reverse endothelial damage and placental dysfunction. Recent studies have examined therapeutic interventions for the treatment of preeclampsia in a high-risk population, based on dietary supplementation with L-arginine in food bars, and antioxidant vitamins (21).…”

mentioning

confidence: 95%

Sildenafil stimulates human trophoblast invasion through nitric oxide and guanosine 3′,5′-cyclic monophosphate signaling

Bolnick

Kilburn

Bolnick

et al. 2015

Fertility and Sterility

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mentioning

confidence: 95%

Sildenafil stimulates human trophoblast invasion through nitric oxide and guanosine 3′,5′-cyclic monophosphate signaling

Bolnick

Kilburn

Bolnick

et al. 2015

Fertility and Sterility

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“…In addition, a dose escalation design meant over half of the women received only the lowest dose of 20 mg three times a day (TDS). No difference was found in the vascular reactivity of myometrial vessels from women receiving sildenafil compared with placebo, possibly because of the interval between the last dose and delivery …”

Section: How Can We Treat Poor Placentation?mentioning

confidence: 93%

Treatment of poor placentation and the prevention of associated adverse outcomes – what does the future hold?

2014

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Poor placentation, which manifests as pre-eclampsia and fetal growth restriction, is a major pregnancy complication. The underlying cause is a deficiency in normal trophoblast invasion of the spiral arteries, associated with placental inflammation, oxidative stress, and an antiangiogenic state. Peripartum therapies, such as prenatal maternal corticosteroids and magnesium sulphate, can prevent some of the adverse neonatal outcomes, but there is currently no treatment for poor placentation itself. Instead, management relies on identifying the consequences of poor placentation in the mother and fetus, with iatrogenic preterm delivery to minimise mortality and morbidity. Several promising therapies are currently under development to treat poor placentation, to improve fetal growth, and to prevent adverse neonatal outcomes. Interventions such as maternal nitric oxide donors, sildenafil citrate, vascular endothelial growth factor gene therapy, hydrogen sulphide donors, and statins address the underlying pathology, while maternal melatonin administration may provide fetal neuroprotection. In the future, these may provide a range of synergistic therapies for pre-eclampsia and fetal growth restriction, depending on the severity and gestation of onset.

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“…The same group performed a parallel study in which they used pressure myography to analyze the relaxation of the arteries extracted from the umbilical cord and the omentum of the study subjects. They found no difference between groups, showing that the drug had no effect on ex vivo samples [60].…”

Section: T H E U S E O F S C a T T H E O N S E T O F P R E E C L A M mentioning

confidence: 96%

Sildenafil for the treatment of preeclampsia, an update: should we still be enthusiastic?

Simon-Tillaux

Lecarpentier

Tsatsaris

et al. 2018

Nephrology Dialysis Transplantation

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Preeclampsia is a hypertensive disorder of pregnancy and the clinical manifestation of severe endothelial dysfunction associated with maternal and foetal morbidity and mortality. The primum movens of the disease is the defect of invasion of the uterine arteries by foetal syncytiotrophoblasts, which causes a maladaptive placental response to chronic hypoxia and the secretion of the soluble form of type 1 vascular growth endothelial factor receptor, also called soluble fms-like tyrosine kinase 1 (sFlt-1), the major player in the pathophysiology of the disease. Among its different effects, sFlt-1 induces abnormal sensitivity of the maternal vessels to the vasoconstrictor angiotensin II. This leads to the hypertensive phenotype, recently shown to be abrogated by the administration of sildenafil citrate, which can potentiate the vasodilatory mediator nitrite oxide. This review focuses on the mechanisms of maternal endothelial dysfunction in preeclampsia and discusses the therapeutic window of sildenafil use in the context of preeclampsia, based on the results from preclinical studies and clinical trials. Safety issues recently reported in neonates have considerably narrowed this window.

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Phosphodiesterase Inhibitor Effect on Small Artery Function in Preeclampsia

Abstract: Acute effects may have been lost as sildenafil administration occurred many hours prior to myography. Plasma sildenafil levels may have been lower than required for vascular response.

Cited by 17 publications

References 15 publications

Sildenafil stimulates human trophoblast invasion through nitric oxide and guanosine 3′,5′-cyclic monophosphate signaling

Sildenafil stimulates human trophoblast invasion through nitric oxide and guanosine 3′,5′-cyclic monophosphate signaling

Treatment of poor placentation and the prevention of associated adverse outcomes – what does the future hold?

Sildenafil for the treatment of preeclampsia, an update: should we still be enthusiastic?

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