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We therefore investigated the placental transfer, vascular effects and anti\u2010inflammatory actions of pentoxifylline in healthy and pre\u2010eclamptic human placentas.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      The placental transfer and metabolism of pentoxifylline were studied using\n                      <jats:italic>ex vivo<\/jats:italic>\n                      placenta perfusion experiments. In wire myography experiments with chorionic plate arteries, pentoxifyllines vasodilator properties were investigated, focusing on the cGMP and cAMP pathways and adenosine receptors. Its effects on inflammatory factors were also studied in placental explants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Pentoxifylline transferred from the maternal to foetal circulation, reaching identical concentrations. The placenta metabolized pentoxifylline into its active metabolite lisofylline (M1), which was released into both circulations. In healthy placentas, pentoxifylline potentiated cAMP\u2010 and cGMP\u2010induced vasodilation, as well as causing vasodilation by adenosine A\n                      <jats:sub>1<\/jats:sub>\n                      antagonism and via NO synthase and PKG. Pentoxifylline also reduced inflammatory factors secretion. In pre\u2010eclamptic placentas, we observed that its vasodilator capacity was preserved, however not via NO\u2010PKG but likely through adenosine signalling. Pentoxifylline neither potentiated vasodilation through cAMP and cGMP, nor suppressed the release of inflammatory factors from these placentas.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>\n                      Pentoxifylline is transferred across and metabolized by the placenta. Its beneficial effects on the NO pathway and inflammation are not retained in pre\u2010eclampsia, limiting its application in this disease, although it could be useful for other placenta\u2010related disorders. Future studies might focus on selective A\n                      <jats:sub>1<\/jats:sub>\n                      receptor antagonists as a new treatment for pre\u2010eclampsia.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.15931","type":"journal-article","created":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T10:28:55Z","timestamp":1658399335000},"page":"5074-5088","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Pentoxifylline as a therapeutic option for pre\u2010eclampsia: a study on its placental effects"],"prefix":"10.1111","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4736-398X","authenticated-orcid":false,"given":"Michelle","family":"Broekhuizen","sequence":"first","affiliation":[{"name":"Division of Neonatology, Department of Paediatrics Erasmus MC University Medical Center  Rotterdam The Netherlands"},{"name":"Division of Pharmacology and Vascular Medicine, Department of Internal Medicine Erasmus MC University Medical Center  Rotterdam The Netherlands"},{"name":"Division of Experimental Cardiology, Department of Cardiology Erasmus MC University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene","family":"de Vries","sequence":"additional","affiliation":[{"name":"Division of Pharmacology and Vascular Medicine, Department of Internal Medicine Erasmus MC University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marja A. 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