Placental effects and transfer of sildenafil in healthy and preeclamptic conditions
| العنوان: | Placental effects and transfer of sildenafil in healthy and preeclamptic conditions |
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| المؤلفون: | Emilie Hitzerd, A.H. Jan Danser, Irwin K.M. Reiss, Michiel A. de Raaf, Michelle Broekhuizen, Katrina M Mirabito Colafella, Marija Glisic, Sinno H.P. Simons, René de Vries, Birgit C. P. Koch, Daphne Merkus, Sam Schoenmakers |
| المساهمون: | Internal Medicine, Pediatrics, Pharmacy, Cardiology, Obstetrics & Gynecology |
| المصدر: | EBioMedicine EBioMedicine, 45, 447-455. Elsevier |
| بيانات النشر: | Elsevier, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Research paper, Vasoreactivity, Placenta, Nitric Oxide Synthase Type II, chemistry.chemical_compound, 0302 clinical medicine, Pre-Eclampsia, Enos, Pregnancy, Cyclic GMP, Placenta perfusion, biology, General Medicine, 3. Good health, Vasodilation, 030220 oncology & carcinogenesis, embryonic structures, cardiovascular system, Female, Sodium nitroprusside, Perfusion, medicine.drug, Adult, medicine.medical_specialty, Sildenafil, Nitric Oxide, General Biochemistry, Genetics and Molecular Biology, Sildenafil Citrate, Nitric oxide, Preeclampsia, 03 medical and health sciences, Vinpocetine, Internal medicine, medicine, Humans, RNA, Messenger, Vinca Alkaloids, Cyclic Nucleotide Phosphodiesterases, Type 5, business.industry, Phosphodiesterase 5 Inhibitors, medicine.disease, biology.organism_classification, Cyclic Nucleotide Phosphodiesterases, Type 1, respiratory tract diseases, 030104 developmental biology, Endocrinology, chemistry, Case-Control Studies, Commentary, business, Ex vivo |
| الوصف: | Background The 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. Methods Ex 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. Findings Sildenafil 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. Interpretation The 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2352-3964 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6eefabe8bbc1d3749cc5d858c08e2314Test https://doi.org/10.1016/j.ebiom.2019.06.007Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6eefabe8bbc1d3749cc5d858c08e2314 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23523964 |
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