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Sildenafil has shown nitric oxide (NO)-independent pleiotropic effects, however the mechanisms involved are unclear. We investigated the protective effects of sildenafil against hypertension in pregnancy and feto-placental growth restriction induced by NO inhibition, and if sodium nitrite-derived NO formation influences sildenafil effects. We evaluated the plasmatic levels of NO metabolites, cyclic guanosine monophosphate (cGMP), oxidative stress and myeloperoxidase, which are involved in endothelial dysfunction during hypertension in pregnancy. Also, we performed in vitro experiments to examine cell viability and NO synthesis in human umbilical vein endothelial cells (HUVECs) cultures incubated with plasma from healthy or hypertensive pregnant rats treated (or not) with both drugs, either alone or in association. Sildenafil blunted hypertension in pregnancy and protected against feto-placental growth …