Papel do sistema renina-angiotensina e do desequilíbrio redox em modelo experimental de pré-eclâmpsia induzida por L-NAME

Abstract

Preeclampsia (PE), a systemic syndrome of pregnancy characterized by proteinuria and hypertension, is associated with significant morbidity and mortality to both mothers and fetuses, however its causes have not been completely clarified. Despite an expressive increase in renin-angiotensin system (RAS) activity in the normal pregnancy, blood pressure does not increase. Nevertheless, the role of RAS in PE is not well known. In PE, the reduction in intrauterine perfusion pressure promotes an increased release of reactive oxygen species, which may contribute to hypertension in pregnancy. In the present study, we investigated the role of the vascular RAS and the plasmatic, cardiorenal and placental oxidative stress to maternal cardiovascular regulation on normal pregnancy and in a animal model of preeclampsia which was induced by L-NAME. The bood pressure was increased in animals which received L-NAME. Pregnant + L-NAME rats had fat loss during pregnancy, increased number of death fetus, decreased number of fetus alive, lower total placental mass and lower pups weight. The vasodilator effect of acetylcholine (Ach) and angiotensin (Ang) II was reduced in pregnant + L-NAME and non-pregnant + L-NAME, otherwise, the vasodilator effect of nitroglycerine (NG) and the vasoconstrictor effect of phenilephrine (Phe) and Ang II were increased. The expression of AT1, AT2, ACE, ACE2 and eNOS were no significantly different among the four groups. The plasma levels of renin and bradykinin (BK) were increased in pregnant + L-NAME rats, while Ang 1-7 was reduced. The serum estradiol was increased in pregnant and pregnant + L-NAME rats. The levels of malondialdehyde and protein carbonyls were increased and activities of antioxidant enzymes SOD and GPx were lower in pregnant + L-NAME and non-pregnant + L-NAME animals, but CAT did now show significant difference among the four groups. In conclusion, the reduced vasodilator responde of Ang II associated to increased vasoconstrictor response of this peptide, suggest that RAS contribute to development of preeclampsia-like characteristics in this model of PE. Similarly, the increase of lipid peroxidation and protein oxidation, as the reduction of antioxidant activity suggest the involvement of a deficient mechanism of antioxidant defense and an increased oxidative damage contributing to development of hypertension, endothelial dysfunction, high fetus mortality and intrauterine growth restriction observed in this model of PE.