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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2014.tde-26062014-165520
Document
Author
Full name
Simone Marcieli Sartoretto
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2014
Supervisor
Committee
Akamine, Eliana Hiromi (President)
Delbin, Maria Andréia
Irigoyen, Maria Claudia Costa
Muscara, Marcelo Nicolas
Porto, Catarina Segreti
Title in Portuguese
Avaliação dos mecanismos envolvidos na redução da contração vascular em aortas de ratas diabéticas: papel da iNOS e insulina.
Keywords in Portuguese
Diabetes
Fêmeas
iNOS
Reatividade vascular
Receptores de estrógeno
Abstract in Portuguese
No presente estudo, observamos aumentada expressão de iNOS e de proteínas s-nitrosiladas (S-NT) em aorta (AO) e concentração de NO no plasma de ratas diabéticas (DB), que foram corrigidas pelo tratamento com insulina (INS), que foi incapaz de normalizar a glicemia. O tratamento com o inibidor da iNOS L-NIL reduziu a expressão de S-NT e a concentração de NO. A contração induzida por agonistas adrenérgicos (ADRs), mas não por cloreto de potássio, que estava reduzida em anéis de AO sem endotélio de ratas DB, foi corrigida pelos tratamentos com INS e L-NIL. A expressão dos receptores de estrógeno ESR2 e GPER estava aumentada em AO de ratas DB e foi corrigida pelo tratamento com INS. Nossos resultados mostram que o aumento da expressão da iNOS/geração de NO é responsável pela redução da contração mediada por receptor ADR, mas não daquela induzida por despolarização direta da membrana. A INS modula negativamente a expressão da iNOS e dos receptores ESR2 e GPER em aorta de ratas DB, efeito que pode contribuir com a restauração da contração induzida por agonistas ADRs.
Title in English
Mechanisms involved in the reduced vascular contraction in aortas of diabetic female rats: a role of iNOS and insulin.
Keywords in English
Diabetes
Estrogen receptors
Female
iNOS
Vascular reactivity
Abstract in English
In the present study, we observed that in aortas (AO) of diabetic (DB) female rats have an increase in iNOS and S-nitrosilated (S-NT) proteins expression along with higher levels of plasmatic NO. Although insulin (INS) treatment did not normalize blood glucose levels, it corrected protein expression and NO concentrations. The iNOS inhibitor treatment reduced the altered expression of S-NT proteins and NO levels. The reduced adrenergic agonists (ADR)-induced contractions in DB without endothelium were corrected by INS and L-NIL treatments, such treatments did not affect the reduced vasoconstriction response to KCl in DB AO. The increase expression of estrogen receptors GPER and ESR2 found in DB AO was recovered by INS treatment. Our results showed that the increased expression of iNOS/NO generation is responsible for reducing ADR-induced contraction, but not for membrane depolarization-induced contraction. INS negatively modulates protein expression of iNOS, ESR2, and GPER receptors in DB AO; such effect may contribute to restore ADR-induced vascular contraction.
 
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Publishing Date
2014-06-27
 
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