EFFECT OF SILDENAFIL ON PREECLAMPSIA-LIKE MOUSE MODEL INDUCED BY L-NAME

MOTTA CE; GROSSO CE; ZANUZZI CN; MOLINERO D; PICCO N; BELLINGERI R; ALUSTIZA F; BARBEITO CG.; VIVAS A; ROMANINI A

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 of3 nitric oxide (NO) and induces preeclampsia in mouse. Sildenafil inhibits the4 degradation of nitric oxide and increases vasodilation. This study aimed to determine5 the effects of sildenafil citrate on angiogenesis and oxidative stress at the maternal fetal6 interface on preeclampsia-like mouse model induced by L-NAME. Twenty pregnant7 mice were divided into 4 groups: 1)Vehicle control; 2)L-NAME; 3)sildenafil; 4)L8NAME+sildenafil. L-NAME was administered from day 7 of pregnancy and sildenafil9 from day 8 until day 16; animals were euthanized on day 17. Placental and fetal sizes10 and weights were measured; lipid peroxide levels and catalase activity in placental11 homogenates were determined, and placental vascular endothelia were identified by12 lectin-histochemistry using BSA-I lectin. Western Blot analysis was used to determine13 VEGF expression in placental homogenates. No changes were seen in placental and14 fetal development in mice with normal pregnancies treated with sildenafil. Treatments15 with L-NAME reduced significantly the placental weight and average height, and16 decrease the percentage of the endothelial surface. These alterations may be mediated17 by the reduction of NO levels in trophoblastic cells, due to the inhibitory effect of L18NAME on nitric oxide synthase (NOS) synthesis. This effect was offset by the19 treatment with sildenafil, with an increase in the percentage of the endothelial surface.20 In conclusion our results indicate that treatment with sildenafil on preeclampsia mouse21 model can be used without adverse effects on the concept and its use in the treatment of22 preeclampsia is promising.