Tadalafil alleviates preeclampsia and fetal growth restriction in RUPP model of preeclampsia in mice

– Tadalafil, a long-acting phosphodiesterase 5 (PDE5) inhibitor, alleviates preeclampsia (PE), and decreases the fetal and infant deaths associated with fetal growth restriction (FGR) in phase II clinical trial. Recently, we demonstrated that tadalafil alleviates FGR and hypertension in the dams wit...

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Veröffentlicht in:Biochemical and biophysical research communications 2020-01, Vol.521 (3), p.769-774
Hauptverfasser: Sekimoto, Akiyo, Tanaka, Kayo, Hashizume, Yamato, Sato, Emiko, Sato, Hiroshi, Ikeda, Tomoaki, Takahashi, Nobuyuki
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Sprache:eng
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Zusammenfassung:– Tadalafil, a long-acting phosphodiesterase 5 (PDE5) inhibitor, alleviates preeclampsia (PE), and decreases the fetal and infant deaths associated with fetal growth restriction (FGR) in phase II clinical trial. Recently, we demonstrated that tadalafil alleviates FGR and hypertension in the dams with PE induced by l-NAME. –The aim of present study was to clarify the effect of tadalafil in another mouse model of PE, murine reduced uterine perfusion pressure (RUPP) model we have recently developed. –At 14.5 dpc we performed RUPP operation in mice to induce PE, administered the animals with tadalafil or vehicle in the drinking water daily from 15.5 dpc, and sacrificed them at 18.5 dpc for analyses. –Tadalafil improved maternal hypertension and glomerular endotheliosis in RUPP mice. Moreover, tadalafil prolonged pregnancy period, and improved survival and growth of the embryos. RUPP increased content of sFlt-1 protein in the placenta, and tadalafil corrected it back to control levels. – Tadalafil alleviates PE-like phenotype and FGR in RUPP murine model. RUPP model could help understand the mechanism of how tadalafil works on PE and FGR. •We used a novel mouse model of preeclampsia (PE), RUPP.•Tadalafil corrected maternal high blood pressure in RUPP PE.•Tadalafil ameliorated endothelial damage in RUPP PE.•Tadalafil prolonged pregnancy period in RUPP PE.•Tadalafil improved survival and growth of embryos in RUPP PE.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2019.10.186