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dc.contributor.author
Ragone, María Inés
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dc.contributor.author
Bayley, Matias
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dc.contributor.author
Colareda, German Andres
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dc.contributor.author
Bonazzola, Patricia
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dc.contributor.author
Consolini, Alicia Elvira
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dc.date.available
2022-12-29T12:44:48Z
dc.date.issued
2020-01
dc.identifier.citation
Ragone, María Inés; Bayley, Matias; Colareda, German Andres; Bonazzola, Patricia; Consolini, Alicia Elvira; Cardioprotective Mechanisms of Hypothyroidism on Ischemia/Reperfusion in Rats and Effects of Carvedilol: Energetic Study; SAGE Publications; Journal Of Cardiovascular Pharmacology And Therapeutics; 25; 1; 1-2020; 72-85
dc.identifier.issn
1074-2484
dc.identifier.uri
http://hdl.handle.net/11336/182807
dc.description.abstract
Hypothyroidism is considered a cardiac risk factor, but there is controversial evidence about its effects on coronary disease. The aim of this work was to evaluate the influence of hypothyroidism in rat hearts exposed to 2 degrees of stunning due to ischemia and reperfusion (I/R) as well as the underlying mechanisms. Hypothyroid (HypoT) rats were obtained by drinking 0.02% methimazole during 15 days. Isolated hearts were perfused and introduced in a flow calorimeter to measure contractile performance (P), total heat rate (Ht), and muscle economy (P/Ht). Hearts were exposed to 2 models of I/R, moderate and severe (respectively 20 or 30 minutes I/45 minutes R). Moreover, free cytosolic and mitochondrial calcium changes were measured by confocal fluorometry on cardiomyocytes. Comparison to euthyroid (EuT) hearts was done. Hypothyroidism was cardioprotective, but HypoT hearts were more sensitive than EuT hearts to the preischemic blockade of mitochondrial transporters mNCX and mKATP channels. Moreover, the postischemic recovery of P and P/Ht in HypoT hearts was strongly reduced by inhibition of the cellular pathways of PI3K/Akt and protein kinase C (PKC), and it was increased by nitric oxide synthase (NOS) inhibition. However, physiological concentrations of adrenaline reduced the cardioprotection of HypoT, but oral treatment with 20 mg/kg/day carvedilol prevented it. Results show that hypothyroidism reduces the mitochondrial Ca2+ overload during I/R by mKATP channel activation and Ca2+ extrusion through mNCX, while the PI3K/Akt and PKC pathways are involved in that cardioprotection. Contrarily, NOS activation and adrenaline blunt such cardioprotection, but carvedilol prevented the adrenergic dysfunction. These results would explain why hypothyroidism is a clinical risk factor in angor patients under adrenergic exacerbation but reduced the incidence of acute episodes of coronary syndrome in hospitalized patients. Results suggest that a treatment with carvedilol could be a potential therapeutic agent to prevent cardiac postischemic dysfunction in hypothyroid patients.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
SAGE Publications
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
CARVEDILOL
dc.subject
HEART
dc.subject
HYPOTHYROIDISM
dc.subject
ISCHEMIA/REPERFUSION
dc.subject
MITOCHONDRIA
dc.subject.classification
Farmacología y Farmacia
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dc.subject.classification
Medicina Básica
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
Cardioprotective Mechanisms of Hypothyroidism on Ischemia/Reperfusion in Rats and Effects of Carvedilol: Energetic Study
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2022-12-28T14:02:17Z
dc.identifier.eissn
1940-4034
dc.journal.volume
25
dc.journal.number
1
dc.journal.pagination
72-85
dc.journal.pais
Estados Unidos
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dc.journal.ciudad
California
dc.description.fil
Fil: Ragone, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Farmacología; Argentina
dc.description.fil
Fil: Bayley, Matias. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Farmacología; Argentina
dc.description.fil
Fil: Colareda, German Andres. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Farmacología; Argentina
dc.description.fil
Fil: Bonazzola, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina
dc.description.fil
Fil: Consolini, Alicia Elvira. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Farmacología; Argentina
dc.journal.title
Journal Of Cardiovascular Pharmacology And Therapeutics
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://journals.sagepub.com/doi/10.1177/1074248419872957
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1177/1074248419872957
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