Avaliação cardiovascular da prole adulta de ratas submetidas à pré-eclâmpsia experimental: efeitos da suplementação materna com o extrato do caroço do açaí (Euterpe oleracea Mart)

Abstract

Preeclampsia (PE) is a multifactorial pregnancy condition that affects fetal development and increases the risk of cardiovascular and renal alterations in adult offspring. The L-NAME-induced PE rodent model reproduces alterations observed in humans. Açaí seed extract (ASE) exhibits antioxidant properties and antihypertensive effects in L-NAME-induced PE mothers. However, its potential to mitigate the long-term effects of intrauterine exposure to PE in offspring remains unclear. Therefore, the objective of this study was to evaluate the cardiovascular and renal systems of male offspring in adulthood from rats subjected to experimental PE and the effects of maternal supplementation with ASE. PE was induced in pregnant Wistar rats (3 months old) by the administration of L-NAME (60 mg/kg/day) from gestational day 13 to 20. The effects of concomitant supplementation with ASE (200 mg/kg/day) on the alterations induced in this model were assessed. The experimental groups were: L-NAME, L-NAME+ASE, Control and Control+ASE. The pups were born naturally and weaned at 21 days of age. The body length and weight of male offspring were evaluated at the beginning of life and in adulthood. Blood pressure was measured weekly from 2 to 4 months of age, and 24-hour urine was collected at the end of the experimental protocol. At 4 months, the offspring were euthanized with isoflurane (4% for hypnosis+ 1L/min O2; 2% maintenance + 0.8 L/min O2), blood was collected via abdominal aorta puncture, and the mesenteric arterial bed and thoracic aorta were isolated for reactivity assessment to vasoactive substances. Biochemical analyses were performed on plasma and urine samples. Additionally, morphological analyses and immunostaining of AT1 receptors and 8-isoprostane were conducted in the thoracic aorta, heart, and left kidney. Oxidative damage (protein carbonylation and lipid peroxidation) and antioxidant enzyme activity were assessed in plasma, heart, and left kidney. The results demonstrated reduced body weight and length at birth in the offspring of PE-subjected rats, with recovery of these parameters still in the perinatal period. In adulthood, PE led to increased blood pressure, renal morphofunctional alterations, and elevated AT1 receptor expression in the aorta, heart, and left kidney, accompanied by greater oxidative damage in tissues and plasma. These effects occurred without changes in circulating angiotensin II levels and did not significantly affect vascular reactivity or the morphology of the aorta and heart. Maternal ASE supplementation attenuated hypertension and renal alterations in L-NAME offspring, while also reducing AT1 receptor immunostaining and oxidative damage in various organs, without impacting antioxidant enzyme activity. These findings highlight the potential of ASE as a preventive intervention to improve maternal-fetal outcomes in PE and to reduce the risks of cardiovascular and renal diseases in adult offspring.