Efeito do extrato do caroço de açaí (Euterpe oleracea Mart.) no desenvolvimento da hipertensão e da disfunção endotelial em modelo experimental de pré-eclâmpsia

Abstract

Preeclampsia (PE) complicates around 5% of pregnancies and is the main cause of maternal and fetal morbidity and mortality. The administration of L-NAME (nitric oxide synthase inhibitor) during rodent pregnancy constitutes a pharmacological model of PE, which presents hypertension, proteinuria and maternal endothelial dysfunction, as well as restriction of fetal growth. Studies of our group showed that the hydroalcoholic extract of the açaí seed (ASE) is rich in polyphenols and points to its antioxidant, vasodilator and antihypertensive actions. This study aims to investigate the preventive effects of ASE on the cardiovascular changes that accompany the experimental PE. The PE was induced in pregnant Wistar rats (3 months) by the administration of L-NAME (60mg / kg / day), from 13th to the 20th day of gestation. We evaluated the effects of concomitant treatment with ASE (200 mg/kg/ day) on cardiovascular changes induced in this model. Four experimental groups were used: L-NAME; L-NAME + ASE; Control; Control + ASE. Blood pressure (BP) was measured once a week by tail plethysmography. Microalbuminuria was evaluated in 24-hour urine, collected on the 19th day of gestation. On day 20, rats were anesthetized with thiopental (50 mg / kg ip), number and weight of live fetuses, as well as total placental mass were evaluated, blood collection was performed for biochemical analyzes, and the mesenteric arterial bed (MAB) was isolated and coupled to an organ perfusion system to evaluate its reactivity to vasoactive substances. Oxidative damage and antioxidant enzyme activity was evaluated in plasma and MAB homogenate. Plasma levels of pro-inflammatory cytokines and anti-angiogenic factor sFLT1 were also evaluated. Protein expression of total eNOS and phosphorylated eNOS (ser1177) was evaluated in MAB by Western blotting. The results showed that ASE prevent the development of hypertension and microalbuminuria in this model, as well as the reduction of placental mass and restriction of fetal growth (p <0.05). ASE also prevented the reduction of the vasodilatory response induced by acetylcholine, bradykinin and angiotensin II in pre-contracted MAB with norepinephrine in the experimental PE (p <0.05). Furthermore, the treatment prevented partially the increase vasoconstrictor response induced by angiotensin II (p <0.05) - but not of noradrenaline in this model. Plasma oxidative damage, evaluated by the formation of lipid peroxidation byproducts (TBARS), was increased in the L-NAME group compared to the control and the ASE prevented this increase (p <0.05). The activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were not different between the groups in plasma samples. On the other hand, the levels of TBARS were lower in MAB of the L-NAME group (p <0.05) and the ASE did not modify this parameter, whereas the carbonyl levels in the MAB did not differ between groups. The activity of the CAT and GPx enzymes were decreased in MAB of the L-NAME and L-NAME + ASE groups (p <0.05), whereas the SOD activity did not differ between groups. Protein expression of total eNOS and its phosphorylated form, as well as plasma levels of pro-inflammatory cytokines and sFlt1 did not differ between groups. The results of the present study demonstrated that ASE treatment prevents the development of hypertension and restriction of fetal growth in PE experimental induced by L-NAME. The beneficial effects can be attributed, at least in part, to its antioxidant action and the improvement of endothelial dysfunction in this model.