Ação hepática da angiotensina II, interação com receptores beta-adrenérgicos e relação com a sinalização da insulina em ratos hipertensos ou submetidos a dieta com elevado teor de frutose

• Ano de defesa: 2017
• Autor(a) principal: Lichtenecker, Débora Conte Kimura [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Angiotensin II; Beta-Adrenergic Receptor; Liver; Shr; Insulin release; Angiotensina II; Receptor beta-adrenérgico; Fígado; Sinalização da Insulina
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=5169975; http://repositorio.unifesp.br/handle/11600/50556

Introduction: The renin-angiotensin-aldosterone system (RAAS) is related to essential hypertension and metabolic syndrome. Many studies have explored the signaling pathways of angiotensin 11 (Angll) and its interaction to other hormones such as insulin and adrenàline. Although the is not considered a target organ in the pathophysiology of hypertension and in the RAAS, Angll has hemodynamic (portal hypertensive response, RHP) and metabolic (glucose release) roles. Objective: To study the hepatic effect of Angll in the presence of antagonists to beta-adrenergic and AT1 receptors in two hypertensive models, as well as to evaluate the expression of angiotensin receptors and IRS-1 phosphorylation in hypertensive rats or high fructose intake model. Methods: Monovascular rat liver perfusion was performed to evaluate the effects of antagonists on the Angll action in two models of hypertension: genetic, spontaneously hypertensive rats (SHR); and pharmacological, chronic inhibition of NO synthase by L-NAME. The RHP (cmH20.min) and the glucose release (umol.q") were evaluated . The angiotensin receptors, phosphorylated IRS-1 and SOCS-3 expression were evaluated by Western Blotting in liver homogenates after Angll infusion in the .., chronic fructose intake model (10% or 30%) and SHR. Statistical analysis was performed using ANOVA, followed by Bonferroni (parametric data) or Kruskal-Wallis followed by Games-Howell (non-parametric data). Results are presented as mean±SEM. Results: Increased blood pressure was confirmed in the pharmacologicaJ model and SHR. In ali groups, the Angll-induced RHP was lower in the presence of losartan but was not altered by the presence of beta-adrenergic receptor antagonists, propranolol or atenolol. In the SHR group the Angll-induced glucose release (5.4±0.6) was lower when compared to the WIS (11.8±0.9, Kruskal-Wallis, P=0.015) and LNAME (11.2±1.5) but normalized in the presence of propranolol (14.1 ±0.9) or atenolol (16.6±2.8) (Kruskal-Wallis, P<0.001 and P=0.035 respectively). On the other hand, in the SHR group in the presence of losartan and its association with propranolol, as well as in the WIS and L-NAME groups in the presence of propranolol or atenolol, the amount of glucose released was similar to the control group. In another series of experiments, it was observed that the chronic intake of fructose (10% or 30%) did not alter the caudal systolic pressure and the animais growth curve, however, hepatic steatosis and increased glycogen content were observed. Fructose (10%) increased triglyceridemia, while 30% increased glycemia and fasting insulinemia. Expression of xxii angiotensin receptors was similar in WIS, Fru 10 and 30% and SHR groups after perfusion in the absence or presence of Angll. To study a possible interaction between the Angll and insulin signaling pathways the protein expression of phosphorylated IRS- 1 was evaluated and only traces of serine phosphorylation at residues 308 and 312 were found. Infusion of Angll did not alter the expression of SOCS- 3 in the 4 groups studied. Conclusion: Our results suggest an interaction between the RAAS and the adrenergic system in the liver of spontaneously hypertensive animais; the high fructose intake does not promote changes in hepatic RAAS.