Effect of Sildenafil on Pre-Eclampsia-Like Mouse Model Induced By L-Name

MOTTA C; GROSSO MC; ZANUZZI CN; MOLINERO D; PICCO N; BELLINGERI R; ALUSTIZA F; BARBEITO C; VIVAS A; ROMANINI MC

REPRODUCTION IN DOMESTIC ANIMALS (1990)

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2015

0936-6768

N(omega)-nitro-L-arginine methyl ester (L-NAME) decreases the vasodilator effect of nitric oxide (NO) and induces preeclampsia in mouse. Sildenafil inhibits the degradation of nitric oxide and increases vasodilation. This study aimed to determine the effects of sildenafil citrate on angiogenesis and oxidative stress at the maternal foetal interface on preeclampsia-like mouse model induced by L-NAME. Twenty pregnant mice were divided into four groups: (i) vehicle control; (ii) L-NAME; (iii) sildenafil; (4) L-NAME+sildenafil. L-NAME was administered from day 7 of pregnancy andsildenafil from day 8 until day 16; animals were euthanized on day 17. Placental and foetal sizes and weights were measured; lipid peroxide levels and catalase activity in placental homogenateswere determined, and placental vascular endothelia were identified by lectin-histochemistry using BSA-I lectin. Western blot analysis was used to determine VEGF expression in placental homogenates. No changes were seen in placental and foetal development in mice with normal pregnancies treated with sildenafil. Treatments with L-NAME reduced significantly the placental weight and average height and decreased the percentage of the endothelial surface. Thesealterations may be mediated by the reduction of NO levels in trophoblastic cells, due to the inhibitory effect of L-NAME on nitric oxide synthase (NOS) synthesis. This effect was offset bythe treatment with sildenafil, with an increase in the percentage of the endothelial surface. In conclusion, our results indicate that treatment with sildenafil on pre-eclampsia mouse modelcan be used without adverse effects on the concept and its use in the treatment of pre-eclampsia is promising.