Melatonin Reduces Oxidative Stress in the Right Ventricle of Newborn Sheep Gestated under Chronic Hypoxia

Abstract

Pulmonary arterial hypertension of newborns (PAHN) constitutes a critical condition involving both severe cardiac remodeling and right ventricle dysfunction. One main cause of this condition is perinatal hypoxia and oxidative stress. Thus, it is a public health concern for populations living above 2500 m and in cases of intrauterine chronic hypoxia in lowlands. Still, pulmonary and cardiac impairments in PAHN lack effective treatments. Previously we have shown the beneficial effects of neonatal melatonin treatment on pulmonary circulation. However, the cardiac effects of this treatment are unknown. In this study, we assessed whether melatonin improves cardiac function and modulates right ventricle (RV) oxidative stress. Ten lambs were gestated, born, and raised at 3600 m. Lambs were divided in two groups. One received daily vehicle as control, and another received daily melatonin (1 mg·kg−1·d−1) for 21 days. Daily cardiovascular measurements were recorded and, at 29 days old, cardiac tissue was collected. Melatonin decreased pulmonary arterial pressure at the end of the experimental period. In addition, melatonin enhanced manganese superoxide dismutase and catalase (CAT) expression, while increasing CAT activity in RV. This was associated with a decrease in superoxide anion generation at the mitochondria and NADPH oxidases in RV. Finally, these effects were associated with a marked decrease of oxidative stress markers in RV. These findings support the cardioprotective effects of an oral administration of melatonin in newborns that suffer from developmental chronic hypoxia.

Cardioprotective Antioxidant and Anti-Inflammatory Mechanisms Induced by Intermittent Hypobaric Hypoxia

“…In addition, for each ventricle wall and IS, we determined the myocardial cellular density as the number of nuclei/area. The analysis of the microphotographs was performed with the software Image Pro-Plus 6.2 (Media Cybernetics Inc., Rockville, MD, USA) [ 22 ].…”

Melatonin and Related Compounds: Antioxidant and Anti-Inflammatory Actions

“…The first paper, by Gonzaléz-Candia et al, investigated the effects of the post-natal administration of melatonin in lambs subjected to gestational hypoxia as a model of pulmonary arterial hypertension of new-borns, specifically evaluating the cardiac function and right ventricle oxidative stress [3]. Neonatal lambs received either melatonin or vehicle for 21 days after birth.…”

Cinaciguat (BAY-582667) Modifies Cardiopulmonary and Systemic Circulation in Chronically Hypoxic and Pulmonary Hypertensive Neonatal Lambs in the Alto Andino

“…However, the mechanisms maintaining pulmonary hypertension were different for each group of newborns. Control newborns exhibited a typical decrease in cardiac output with age and PVR continuation ( Gonzaléz-Candia et al, 2021 ). Conversely, PVR decreased in Cinaciguat treated newborns, but they maintained their cardiac output.…”