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Thèse de Doctorat
DOI
10.11606/T.42.2010.tde-14012011-162359
Document
Auteur
Nom complet
Núbia de Souza Lobato
Unité de l'USP
Domain de Connaissance
Date de Soutenance
Editeur
São Paulo, 2010
Directeur
Jury
Fortes, Zuleica Bruno (Président)
Carvalho, Maria Helena Catelli de
Davel, Ana Paula Couto
Franco, Maria do Carmo Pinho
Scavone, Cristoforo
Titre en portugais
A obesidade diminui a resposta de artérias mesentéricas de resistência a agonistas canabinóides.
Mots-clés en portugais
Endotélio vascular
Obesidade
Relaxamento
Vasos sanguíneos
Resumé en portugais
Este estudo investigou o efeito da obesidade sobre a resposta de artérias mesentéricas a agonistas canabinóides. Ratos obesos Zucker (OZRs) apresentaram reduzido relaxamento à anandamida, aos agonistas CB1 e CB2 e à capsaicina (agonista vanilóide) comparados aos controles (LZRs). A expressão dos receptores CB1 e CB2 foi menor em OZRs. O bloqueio de canais de K+, a inibição da NOS, da COX ou do transporte de canabinóides reduziu a resposta à anandamida em LZRs. A resposta à anandamida em OZRs foi corrigida após: inibição da degradação de anandamida, ativação da via do cAMP e da AMPK, e inibição da ERK1/2. A anandamida aumentou a fosforilação da AMPK, da ACC e da eNOS em LZRs, mas reduziu em OZRs. A expressão da ERK1/2 fosforilada, maior em OZRs, foi potencializada pela anandamida. A obesidade diminui o relaxamento à anandamida por: reduzir a expressão de receptores CB1 e CB2; prejudicar respostas mediadas por receptores vanilóides; reduzir a captação e aumentar a degradação de anandamida; reduzir a ativação da AMPK e da eNOS e aumentar da ativação da ERK1/2.
Titre en anglais
Obesity decreases the response of resistance mesenteric arteries to cannabinoid agonists.
Mots-clés en anglais
Blood vessels
Obesity
Relaxation
Vascular endothelium
Resumé en anglais
This study aimed to investigate the effects of obesity on the response of mesenteric arteries to cannabinoid agonists. Obese Zucker rats (OZRs) displayed decreased relaxation to anandamide, to CB1 and CB2 agonists as well as to capsaicin (vanilloid agonist) compared to lean rats (LZRs). The CB1 and CB2 expression was decreased in OZRs. Anandamide response was decreased in LZRs after blockade of K+ channels and inhibition of NOS, COX or cannabinoid transport. Anandamide response in OZRs was corrected by: inhibition of anandamide degradation, activation of cAMP and AMPK pathway and inhibition of ERK1/2. Anandamide increased AMPK, ACC and eNOS phosphorylation in LZRs, but it reduced in OZRs. The expression of phosphorylated ERK1/2, increased in OZRs, was potentiated by anandamide. In conclusion, obesity decreases anandamide relaxation through: reduction of CB1 and CB2 receptors; impairment of signaling pathways mediated by vanilloid receptors; reduced uptake and increased degradation of anandamide; reduction of AMPK/eNOS activation and increase in ERK1/2 activation.
 
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Date de Publication
2011-05-16
 
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