AUTHOR=Beñaldo Felipe A. , Llanos Aníbal J. , Araya-Quijada Claudio , Rojas Auristela , Gonzalez-Candia Alejandro , Herrera Emilio A. , Ebensperger Germán , Cabello Gertrudis , Valenzuela Guillermo J. , Serón-Ferré María 

TITLE=Effects of Melatonin on the Defense to Acute Hypoxia in Newborn Lambs

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 10 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2019.00433

DOI=10.3389/fendo.2019.00433

ISSN=1664-2392

ABSTRACT=Neonatal lambs, as other neonates, have physiologically a very low plasma melatonin concentration throughout the 24-h. Previously, we found that melatonin given for 5 days decreased heart’s weight, changed plasma cortisol and gene expression in the adrenal and heart. Whether these changes could compromise the responses to life challenges is not known. Therefore, firstly we studied acute effects of melatonin on the defense mechanisms to acute hypoxia in the neonate. Eleven lambs, 2 weeks old were instrumented and submitted to an episode of acute isocapnic hypoxia, consisting of four 30 min periods: normoxia (room air); normoxia after an i.v. bolus of melatonin (0.27 mg kg-1, n= 6) or vehicle (ethanol 1:10 NaCl 0.9%, n = 5); hypoxia (PaO2: 30 ± 2 mmHg), and recovery (room air). Mean pulmonary and systemic blood pressures, heart rate, cardiac output were measured, and systemic, pulmonary vascular resistance and stroke volume were calculated. Blood samples were taken every 30 min to measure plasma norepinephrine, cortisol, glucose, triglycerides and redox markers (8-isoprostane and FRAP). Melatonin blunted the increase of pulmonary vascular resistance triggered by hypoxia, markedly exacerbated the heart rate response, decreasing heart stroke volume and lessened the magnitude of the increase of plasmatic norepinephrine and cortisol levels induced by hypoxia. No changes were observed in the pulmonary blood pressure, systemic blood pressures and resistance, cardiac output, glucose, triglycerides plasma concentrations and redox markers. Melatonin had no effect on cardiovascular, endocrine or metabolic variables, under normoxia. Secondly, we examined whether acute melatonin administration under normoxia could have an effect in gene expression on the adrenal, lung, and heart. Lambs received a bolus of vehicle or melatonin and were euthanized 30 min later to collect tissues. We found that melatonin affected expression of the immediate early genes egr1 in adrenal and ctgf in lung and of nr3c1, the glucocorticoid receptor in adrenal and heart. We speculate that these early genes responses may contribute to the observed alterations of the newborn defense mechanisms to hypoxia. This could be particularly important since the use of melatonin is proposed for several diseases in the neonatal period in humans.