Melatonin improves cerebrovascular function and decreases oxidative stress in chronically hypoxic lambs
Author
dc.contributor.author
Herrera Videla, Emilio
Author
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Macchiavello, Roberto
es_CL
Author
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Montt, Camilo
es_CL
Author
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Ebensperger Darrouy, Germán
es_CL
Author
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Díaz Navarrete, Marcela
es_CL
Author
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Ramírez, Santiago
es_CL
Author
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Parer, Julian T.
es_CL
Author
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Serrón Ferré, María
es_CL
Author
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Reyes, Roberto V.
es_CL
Author
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Llanos Mansilla, Jorge
es_CL
Admission date
dc.date.accessioned
2014-12-11T15:25:34Z
Available date
dc.date.available
2014-12-11T15:25:34Z
Publication date
dc.date.issued
2014
Cita de ítem
dc.identifier.citation
J. Pineal Res. 2014; 57:33–42
en_US
Identifier
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Doi:10.1111/jpi.12141
Identifier
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https://repositorio.uchile.cl/handle/2250/129338
General note
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Artículo de publicación ISI
en_US
Abstract
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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 FiO2 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 PO2 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/lm2, 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.
en_US
Patrocinador
dc.description.sponsorship
This work was supported by National Fund for Scientific
and Technological Development (FONDECYT-Chile),
Grants number 1110595, 1120605, 1130424, 1140647.