El tratamiento postnatal con melatonina modula la expresión de agentes prostanoides en pulmón de neonatos de oveja con hipertensión pulmonar

Abstract

Melatonin modulates the expression of pulmonary prostanoids Background: Living above 2,500 meters in hypobaric conditions induces pulmonary arterial hypertension of the neonate (PAHN), a syndrome whose main features are: pathological remodeling of the pulmonary vessels, abnormal vascular reactivity and increased oxidative stress. Melatonin could have pulmonary antioxidant, anti-remodeling and vasodilating properties for this condition. Aim: To determine the effect of melatonin at the transcript level of prostanoid pathways in the lung of neonatal lambs gestated and born under hypobaric hypoxia. Material and Methods: Vehicle (1.4% of ethanol, n = 6) or melatonin (1 mg * kg-1 , n = 5) were administered from the postnatal day 4 to 21 to lambs gestated and born at 3,600 meters above sea level. After one week of treatment completion, lung tissue was obtained, the transcript and protein levels of prostanoid synthases and receptors were assessed by RT-PCR and Western Blot. Results: Melatonin induced the expression of prostacyclin synthase transcript and increased protein expression of the prostacyclin receptor. In addition, the treatment decreased the expression of transcript and protein of cyclooxygenase-2, without changes in the expression of the prostanoid vasoconstrictor (thromboxane) pathway. Conclusions: Postnatal treatment with melatonin increases the expression of the prostacyclin-vasodilator pathway without changing the vasoconstrictor thromboxane pathway. Further, the decreased COX-2 induced by melatonin could be an index of lesser oxidative stress and inflammation in the lung.

Comment on Melatonin as a potential adjuvant treatment for COVID-19

“…The latter was associated with increased nitric oxide -dependent and -independent vasodilator functions. Interestingly, one of the nitric oxide independent affected mechanisms, was the enhanced expression of the prostacyclin vasodilator pathway [3,4]. The aforementioned findings were also associated with increased expression and/or activity of the endogenous antioxidant enzymes, superoxide dismutase and catalase, an enhanced plasma antioxidant capacity and a marked decreased in pulmonary oxidative stress markers [2,3].…”

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

“…Our findings may explain previous studies that described the direct vasodilator effects of melatonin [ 33 , 78 ]. In addition, melatonin modulates the release of NO, reducing peroxynitrite formation and offer protection from nitrosative/oxidative damage [ 78 ], as well as favoring an increased vasodilation in pulmonary arteries via COX1-PGIs-IP pathway [ 79 ]. Studies undertaken in several animal models have indicated that melatonin has dual effects on the vasculature, with vasoconstriction being observed through MT1 receptor activation and vasodilatation through MT2 receptor [ 28 , 80 , 81 ].…”

Protection by melatonin in respiratory diseases: valuable information for the treatment of COVID-19

“…Further details have been reviewed elsewhere (40). Two recent pre-clinical studies concern protection by melatonin in the perinatal phase of lambs (41,42) and are of particular interest to corresponding investigations in humans (cf. subsequent section).…”

“…subsequent section). Melatonin was administered to lambs born at an altitude of 3,600 meters, i.e., under hypobaric conditions, between 4 and 21 postnatal days (41). In these animals, melatonin enhanced the expression of prostacyclin synthase mRNA and prostacyclin receptor at protein level, components of a vasodilator pathway, whereas vasoconstriction via the thromboxane pathway was not affected.…”