Influência do bloqueio de receptores do tipo 1 (AT1) sobre o perfil metabólico, endócrino e cardiovascular de ratos obesos
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Data
2011-12-19
Autores
Oliveira Júnior, Silvio Assis de [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
Variados agentes moleculares ativam mecanismos determinantes de alterações teciduais do coração, com frequente ocorrência de interação bioquímica entre estímulos distintos, como vigente entre angiotensina II (Ang-II) e insulina. A sinalização molecular principiada pela Ang-II é carreada a partir do acoplamento com receptores do tipo 1 (AT1) e culmina na ativação de proteínas quinases ativadas do mitógeno (MAPK), como extracellular signal-regulated (ERK) e c-Jun N-terminal (JNK). Em analogia, a ação da insulina sobre o receptor de insulina ( RI) determina a estimulação de respostas proliferativas e efeitos vinculados ao metabolismo de macro e micronutrientes. Por meio da ativação de receptores AT1, a Ang-II interfere na sinalização da insulina, regulando a fosforilação de tirosina e dessensibilizando três mensageiros de estímulos metabólicos: o receptor ( RI), o substrato receptor de insulina (IRS) e o peptídeo fosfatidil inositol 3 quinase (PI3K). Embora essas manifestações configurem importantes mecanismos de resistência à insulina na obesidade, não foram encontrados estudos abordando essa relação em modelos experimentais de obesidade exógena. O objetivo deste trabalho foi testar a hipótese de que a obesidade acarreta distúrbios metabólicos, endócrinos e cardiovasculares, incluindo remodelação e resistência insulínica cardíaca, decorrentes da ativação de receptores AT1. Ratos Wistar-Kyoto foram distribuídos em dois grupos: C e OB; ambos os grupos C e OB receberam, respectivamente, dietas padrão e hipercalórica durante 30 semanas. Na sequência, os grupos foram separados em quatro grupamentos: C, C+Los, OB e OB+Los. Ambos os grupos +Los foram tratados com losartan (30 mg/kg/dia), um fármaco antagonista de receptores AT1, no decorrer de cinco semanas,. Subsequentemente, além da...
Several molecular agents trigger cytosolic mechanisms of cardiac remodeling, with common occurrence of biochemical interaction between different stimuli, as observed between angiotensin II (Ang-II) and insulin. The molecular signaling from Ang-II is carried through the coupling of the receptor type 1 (AT1) and culminates in the activation of the mitogen activated protein kinases (MAPK), including extracellular signal-regulated (ERK) and c-Jun N-terminal (JNK). Similarly, the action of insulin on the insulin receptor ( RI) determines the stimulation of proliferative responses and multiple effects linked to metabolism of macro and micronutrients. Through activation of AT1 receptors, Ang-II interferes with insulin signaling by regulating the phosphorylation of three messengers of metabolic stimuli from insulin: the receptor ( IR), insulin receptor substrate (IRS) and phosphatidil inositol 3-kinase (PI3K). Although these events configure important mechanisms of insulin resistance in obesity, there are no studies addressing this relationship in experimental models of exogenous obesity. This study investigated whether obesity causes metabolic, endocrine and cardiovascular diseases, including insulin resistance and cardiac remodeling, due activation of AT1 receptors. Wistar-Kyoto rats (n=40) were subjected to control (C) or hypercaloric diet (OB) for 30 weeks and then assigned to four groups: C, C+Los, OB, and OB+Los. Los-groups received losartan (30mg/kg/day) during five weeks. Afterward, besides the nutritional and biometric analyzes, glycemia, lipids, insulin, leptin and activity of angiotensin-converting enzyme were also evaluated. In vivo cardiovascular study included systolic blood pressure (SBP) and echocardiographic evaluation of ventricular structure and function. Post mortem cardiovascular profile integrated analysis of ventricular... (Complete abstract click electronic access below)
Several molecular agents trigger cytosolic mechanisms of cardiac remodeling, with common occurrence of biochemical interaction between different stimuli, as observed between angiotensin II (Ang-II) and insulin. The molecular signaling from Ang-II is carried through the coupling of the receptor type 1 (AT1) and culminates in the activation of the mitogen activated protein kinases (MAPK), including extracellular signal-regulated (ERK) and c-Jun N-terminal (JNK). Similarly, the action of insulin on the insulin receptor ( RI) determines the stimulation of proliferative responses and multiple effects linked to metabolism of macro and micronutrients. Through activation of AT1 receptors, Ang-II interferes with insulin signaling by regulating the phosphorylation of three messengers of metabolic stimuli from insulin: the receptor ( IR), insulin receptor substrate (IRS) and phosphatidil inositol 3-kinase (PI3K). Although these events configure important mechanisms of insulin resistance in obesity, there are no studies addressing this relationship in experimental models of exogenous obesity. This study investigated whether obesity causes metabolic, endocrine and cardiovascular diseases, including insulin resistance and cardiac remodeling, due activation of AT1 receptors. Wistar-Kyoto rats (n=40) were subjected to control (C) or hypercaloric diet (OB) for 30 weeks and then assigned to four groups: C, C+Los, OB, and OB+Los. Los-groups received losartan (30mg/kg/day) during five weeks. Afterward, besides the nutritional and biometric analyzes, glycemia, lipids, insulin, leptin and activity of angiotensin-converting enzyme were also evaluated. In vivo cardiovascular study included systolic blood pressure (SBP) and echocardiographic evaluation of ventricular structure and function. Post mortem cardiovascular profile integrated analysis of ventricular... (Complete abstract click electronic access below)
Descrição
Palavras-chave
Angiotensina, Obesidade - Metabolismo, Coração
Como citar
OLIVEIRA JÚNIOR, Silvio Assis de. Influência do bloqueio de receptores do tipo 1 (AT1) sobre o perfil metabólico, endócrino e cardiovascular de ratos obesos. 2011. 125 f. Tese (doutorado) - Universidade Estadual Paulista, Faculdade de Medicina de Botucatu, 2011.