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Melatonin improves cerebrovascular function and decreases oxidative stress in chronically hypoxic lambs
Author(s) -
Herrera Emilio A.,
Macchiavello Roberto,
Montt Camilo,
Ebensperger Germán,
Díaz Marcela,
Ramírez Santiago,
Parer Julian T.,
SerónFerré María,
Reyes Roberto V.,
Llanos Aníbal J.
Publication year - 2014
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12141
Subject(s) - melatonin , endocrinology , medicine , oxidative stress , cerebral arteries , anesthesia
Chronic hypoxia during gestation and delivery results in oxidative stress and cerebrovascular dysfunction in the neonate. We assessed whether melatonin, a potent antioxidant and potential vasodilator, improves the cerebral vascular function in chronically hypoxic neonatal lambs gestated and born in the highlands (3600 m). Six lambs received melatonin (1 mg/kg per day oral) and six received vehicle, once a day for 8 days. During treatment, biometry and hemodynamic variables were recorded. After treatment, lambs were submitted to a graded FiO 2 protocol to assess cardiovascular responses to oxygenation changes. At 12 days old, middle cerebral arteries ( MCA ) were collected for vascular reactivity, morphostructural, and immunostaining evaluation. Melatonin increased fractional growth at the beginning and improved carotid blood flow at all arterial PO 2 levels by the end of the treatment ( P < 0.05). Further, melatonin treatment improved vascular responses to potassium, serotonin, methacholine, and melatonin itself ( P < 0.05). In addition, melatonin enhanced the endothelial response via nitric oxide‐independent mechanisms in isolated arteries (162 ± 26 versus 266 ± 34 AUC , P < 0.05). Finally, nitrotyrosine staining as an oxidative stress marker decreased in the MCA media layer of melatonin‐treated animals (0.01357 ± 0.00089 versus 0.00837 ± 0.00164 pixels/ μ m 2 , P < 0.05). All the melatonin‐induced changes were associated with no systemic cardiovascular alterations in vivo. In conclusion, oral treatment with melatonin modulates cerebral vascular function, resulting in a better cerebral perfusion and reduced oxidative stress in the neonatal period in chronically hypoxic lambs. Melatonin is a potential therapeutic agent for treating cerebrovascular dysfunction associated with oxidative stress and developmental hypoxia in neonates.