Tadalafil Improves L-NG-Nitroarginine Methyl Ester-Induced Preeclampsia With Fetal Growth Restriction-Like Symptoms in Pregnant Mice
| Autor: | Eiji Kondo, Masahiro Okuda, Shintaro Maki, Yuki Kamimoto, Kayo Tanaka, Takashi Umekawa, Kenji Ikemura, Hiroaki Tanaka, Kan Katayama, Masafumi Nii, Toshimichi Yoshida, Takekazu Miyoshi, Kento Yoshikawa, Michiko Kubo, Tomoaki Ikeda, Ning Ma, Hiroshi Hosoda, Kazuhiro Osato |
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| Rok vydání: | 2017 |
| Předmět: |
Placental growth factor
medicine.medical_specialty medicine.drug_mechanism_of_action Placenta Blood Pressure 030204 cardiovascular system & hematology Kidney medicine.disease_cause Tadalafil Preeclampsia Fetal Development Mice 03 medical and health sciences 0302 clinical medicine Pre-Eclampsia Pregnancy Internal medicine Internal Medicine Fetal growth Animals Medicine Enzyme Inhibitors Cyclic GMP reproductive and urinary physiology Fetal Growth Retardation 030219 obstetrics & reproductive medicine Proteinuria business.industry Phosphodiesterase 5 Inhibitors medicine.disease Mice Inbred C57BL Oxidative Stress NG-Nitroarginine Methyl Ester Blood pressure Endocrinology Female medicine.symptom business Phosphodiesterase 5 inhibitor Oxidative stress medicine.drug |
| Zdroj: | American Journal of Hypertension. 31:89-96 |
| ISSN: | 1941-7225 0895-7061 |
| Popis: | BACKGROUND We investigated the efficacy and mechanisms of tadalafil, a selective phosphodiesterase 5 inhibitor, in treating preeclampsia (PE) with fetal growth restriction (FGR) using L-NG-nitroarginine methyl ester (L-NAME)-induced PE with FGR in pregnant mice as our experimental model. METHODS C57BL/6 mice were divided into 2 groups 11 days postcoitum (d.p.c.). A control group of dams (C dam) received 0.5% carboxymethylcellulose (CMC). A L-NAME-treated group received 1 mg/ml L-NAME dissolved in CMC. The L-NAME-treated dams were divided into 2 subgroups 13 d.p.c. One subgroup continued to receive L-NAME (L dams). The other subgroup received L-NAME with 0.08 mg/ml tadalafil suspended in CMC (TL dams). Maternal systolic blood pressure (SBP) and proteinuria were assessed 16 d.p.c. Fetal weight was recorded, and placentas and maternal kidneys were collected 17 d.p.c. RESULTS Maternal SBP, proteinuria, and fetal weight were improved for TL dams compared to L dams. The placental concentration of placental growth factor (PlGF) was higher for TL dams than for the C and L dams. The placental maternal blood sinuses of L dams were narrower than those of C dams, but those of TL dams improved to a similar width as C dams. Glomerular oxidative stress was ameliorated in TL dams compared to L dams. CONCLUSIONS Tadalafil dilates the placental maternal blood sinuses, which leads to increase PlGF production, and contributes to facilitate fetal growth and improve maternal SBP. Moreover, tadalafil ameliorates glomerular damage by reducing oxidative stress. These results suggest that tadalafil is a candidate for treatment of PE with FGR. |
| Databáze: | OpenAIRE |
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