ArticleEBioMedicine2019
Placental effects and transfer of sildenafil in healthy and preeclamptic conditions.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Childhood outcomes after maternal antenatal sildenafil treatment for severe early-onset fetal growth restriction: a randomized trial (STRIDER NZAus).Journal of perinatology : official journal of the California Perinatal Association · 2024Trial
- Omeprazole Administration in Preterm Preeclampsia: a Randomized Controlled Trial to Study Its Effect on sFlt-1 (Soluble Fms-Like Tyrosine Kinase-1), PlGF (Placental Growth Factor), and ET-1 (Endothelin-1).Hypertension (Dallas, Tex. : 1979) · 2022Trial
- Pharmacokinetics of betamethasone in pre-eclampsia: An in vivo and ex vivo study.British journal of clinical pharmacology · 2025Article
- Placental Endocannabinoid System: Focus on Preeclampsia and Cannabis Use.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Strategy advancements in placental pharmacokinetics: fromFrontiers in pharmacology · 2025Review
- Impacts of Maternal Preeclampsia Exposure on Offspring Neuronal Development: Recent Insights and Interventional Approaches.International journal of molecular sciences · 2024Review
- 3D human tissue models and microphysiological systems for HIV and related comorbidities.Trends in biotechnology · 2024Review
- Statins Prevent the Deleterious Consequences of Placental Chemerin Upregulation in Preeclampsia.Hypertension (Dallas, Tex. : 1979) · 2024Article
- Endothelial Nitric Oxide synthase (eNOS) in Preeclampsia: An Update.Journal of pregnancy and child health · 2024Article
- In vivo noninvasive systemic myography of acute systemic vasoactivity in female pregnant mice.Nature communications · 2023Article
- Pentoxifylline as a therapeutic option for pre-eclampsia: a study on its placental effects.British journal of pharmacology · 2022Article
- Sildenafil during the 2nd and 3rd Trimester of Pregnancy: Trials and Tribulations.International journal of environmental research and public health · 2022Review
- Transplacental Zika virus transmission in ex vivo perfused human placentas.PLoS neglected tropical diseases · 2022Article
- Placental trophoblast-specific overexpression of chemerin induces preeclampsia-like symptoms.Clinical science (London, England : 1979) · 2022Article
- Placental Ischemia Says "NO" to Proper NOS-Mediated Control of Vascular Tone and Blood Pressure in Preeclampsia.International journal of molecular sciences · 2021Review
- Megalin, Proton Pump Inhibitors and the Renin-Angiotensin System in Healthy and Pre-Eclamptic Placentas.International journal of molecular sciences · 2021Article
- Placental Function and the Development of Fetal Overgrowth and Fetal Growth Restriction.Obstetrics and gynecology clinics of North America · 2021Review
- Current State of Preeclampsia Mouse Models: Approaches, Relevance, and Standardization.Frontiers in physiology · 2021Review
- PAPP-A2 and Inhibin A as Novel Predictors for Pregnancy Complications in Women With Suspected or Confirmed Preeclampsia.Journal of the American Heart Association · 2020Observational
- Larger First-Trimester Placental Volumetric Parameters Are Associated With Lower Pressure and More Flow-Mediated Vasodilation of the Fetoplacental Vasculature After Delivery.Frontiers in physiology · 2020Article
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Authors and funding
12 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe phosphodiesterase-5 inhibitor (PDE5) sildenafil has emerged as a promising treatment for preeclampsia (PE). However, a sildenafil trial was recently halted due to lack of effect and increased neonatal morbidity.
methodsEx vivo dual-sided perfusion of an isolated cotyledon and wire-myography on chorionic plate arteries were performed to study the effects of sildenafil and the non-selective PDE inhibitor vinpocetine on the response to the NO donor sodium nitroprusside (SNP) under healthy and PE conditions. Ex vivo perfusion was also used to study placental transfer of sildenafil in 6 healthy and 2 PE placentas. Furthermore, placental mRNA and protein levels of eNOS, iNOS, PDE5 and PDE1 were quantified.
findingsSildenafil and vinpocetine significantly enhanced SNP responses in chorionic plate arteries of healthy, but not PE placentas. Only sildenafil acutely decreased baseline tension in arteries of both healthy and PE placentas. At steady state, the foetal-to-maternal transfer ratio of sildenafil was 0·37 ± 0·03 in healthy placentas versus 0·66 and 0·47 in the 2 PE placentas. mRNA and protein levels of PDE5, eNOS and iNOS were comparable in both groups, while PDE1 levels were lower in PE.
interpretationThe absence of sildenafil-induced NO potentiation in arteries of PE placentas, combined with the non-PDE-mediated effects of sildenafil and the lack of PDE5 upregulation in PE, argue against sildenafil as the preferred drug of use in PE. Moreover, increased placental transfer of sildenafil in PE might underlie the neonatal morbidity in the STRIDER trial. FUND: This study was funded by an mRACE Erasmus MC grant.
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