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Effect of Sildenafil on Pre‐Eclampsia‐Like Mouse Model Induced By L‐Name
Author(s) -
Motta C,
Grosso C,
Zanuzzi C,
Molinero D,
Picco N,
Bellingeri R,
Alustiza F,
Barbeito C,
Vivas A,
Romanini MC
Publication year - 2015
Publication title -
reproduction in domestic animals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.546
H-Index - 66
eISSN - 1439-0531
pISSN - 0936-6768
DOI - 10.1111/rda.12536
Subject(s) - sildenafil , nitric oxide , medicine , endocrinology , vasodilation , placenta , chemistry , nitric oxide synthase , andrology , biology , pregnancy , fetus , genetics
Contents N(omega)‐nitro‐ L ‐arginine methyl ester ( L ‐ NAME ) decreases the vasodilator effect of nitric oxide ( NO ) and induces pre‐eclampsia 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 pre‐eclampsia‐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 and sildenafil 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 homogenates were 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. These alterations 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 by the 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 model can be used without adverse effects on the concept and its use in the treatment of pre‐eclampsia is promising.