Oxidative damage and nitric oxide synthase induction by surgical uteroplacental circulation restriction in the rabbit fetal heart

Horacio Figueroa, Cristobal Alvarado, Jorge Cifuentes, Mauricio Lozano, Jocelyn Rocco, Claudia Cabezas, Sebastián Illanes, Elisenda Eixarch, Edgar Hernández-Andrade, Eduard Gratacós, Carlos Ernesto Irarrazabal Muñoz

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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-1α, 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.

Original languageEnglish
Pages (from-to)453-459
Number of pages7
JournalPrenatal Diagnosis
Volume37
Issue number5
DOIs
StatePublished - May 2017

Bibliographical note

Publisher Copyright:
© 2017 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

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