Gonzaléz-Candia Alejandro, Arias Pamela V, Aguilar Simón A, Figueroa Esteban G, Reyes Roberto V, Ebensperger Germán, Llanos Aníbal J, Herrera Emilio A
Laboratory of Vascular Function and Reactivity, Pathophysiology Program, ICBM, Faculty of Medicine, Universidad de Chile, Av. Salvador 486, Santiago 7500922, Chile.
Institute of Health Sciences, University of O'Higgins, Libertador Bernardo O'Higgins 611, Rancagua 2820000, Chile.
Antioxidants (Basel). 2021 Oct 22;10(11):1658. doi: 10.3390/antiox10111658.
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·d) 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.
新生儿肺动脉高压（PAHN）是一种严重的疾病，涉及严重的心脏重塑和右心室功能障碍。这种疾病的一个主要原因是围产期缺氧和氧化应激。因此，对于生活在海拔2500米以上的人群以及低地宫内慢性缺氧的情况来说，这是一个公共卫生问题。然而，PAHN中的肺部和心脏损伤缺乏有效的治疗方法。此前我们已经证明了新生儿褪黑素治疗对肺循环有益。然而，这种治疗对心脏的影响尚不清楚。在本研究中，我们评估了褪黑素是否能改善心脏功能并调节右心室（RV）氧化应激。十只羔羊在3600米处妊娠、出生并饲养。羔羊被分为两组。一组每天接受载体作为对照，另一组每天接受褪黑素（1毫克·千克·天），持续21天。记录每日心血管测量数据，并在29日龄时收集心脏组织。实验期结束时，褪黑素降低了肺动脉压。此外，褪黑素增强了锰超氧化物歧化酶和过氧化氢酶（CAT）的表达，同时增加了RV中的CAT活性。这与RV中线粒体和NADPH氧化酶超氧阴离子生成的减少有关。最后，这些效应与RV中氧化应激标志物的显著降低有关。这些发现支持了口服褪黑素对患有发育性慢性缺氧的新生儿的心脏保护作用。
