Oxidative damage and nitric oxide synthase induction by surgical uteroplacental circulation restriction in the rabbit fetal heart. (4th April 2017) - Figueroa, Horacio
Abstract: Objective: This study investigated the role of oxidative damage and nitric oxide (NO) synthases in the fetal heart using a model of intrauterine growth restriction induced by uteroplacental circulation restriction (UCR). Methods: New Zealand white rabbits kept under 12‐h light cycles, with food and water provided ad libitum, were subjected at day 25 of pregnancy to 40–50% uteroplacental artery ligation. We analyzed the gene expression of enzymes linked to nitric oxide synthesis (iNOS, eNOS, HO‐1, and ARG‐2), hypoxia inducible factor 1 alpha (HIF‐1α), and the state of oxidative stress (protein carbonyl levels) in fetal heart homogenates. Additionally, we studied the histological morphology of the fetal heart. Results: We found that fetal growth restriction was associated with a significant reduction in heart weight but a normal heart/body weight ratio in UCR animals. Hematoxylin and eosin staining showed normal left and right ventricular thickness but increased vessel dilatation with hyperemia in the hearts of the UCR group. We observed HIF‐1 α, eNOS, p‐eNOS, and iNOS induction concomitant with intensified protein carbonyl levels but observed no changes in HO‐1 or ARG‐2 expression, suggesting increased NO and oxidative stress in the hearts of UCR animals. Conclusion: Uteroplacental circulation restriction increased NO‐linked enzymes, oxidative damage, and dilated coronary vessels in fetal hearts. © 2017 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd. Abstract : What's Already Known about This Topic? The brain, heart, liver, and kidney are all affected during intrauterine growth restriction. What Does This Study Add? The present study demonstrates, for the first time, alterations in nitric oxide production enzymes and oxidative stress damage in the hearts of fetuses subjected to uteroplacental circulation restriction. Our study provides important insights into the impact of uteroplacental circulation restriction in the fetal heart. Despite the effort to improve heart perfusion, increased oxidative damage was observed during the final state of fetal uterine gestation.