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Vasoactive peptides action in the liver of rats submitted to different experimental models of disease

Grant number: 11/13974-8
Support type:Regular Research Grants
Duration: November 01, 2011 - April 30, 2014
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Maria Kouyoumdjian
Grantee:Maria Kouyoumdjian
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Assoc. researchers:João Bosco Pesquero ; Márcia Regina Nagaoka

Abstract

In the Laboratory of Experimental Hepatology we studied the hepatic reaction by the vasoactive peptide constituents of the kallikrein-kinin and renin-angiotensin system. The main experimental model has been the rat isolated perfused liver that allows the study of the intact organ. To this technique have been correlated to in vitro studies as well as isolated liver cells.We found that in the liver, the bradykinin (BK) has vasoconstrictor response and the portal hypertensive (RHP) is mediated by B2 receptors, but not by B1 receptor (B1R) in both normal rat and those subjected to different agents of liver injury, although during the process of liver cirrhosis and hepatoctemia there is increased expression of B1R, suggesting a role of this receptor in these processes. Recent results show that B1R participate in the fibrogenesis differently depending on the stimulus: CCl4 induces fibrosis in B1R-knockout mice higher than induction by bile duct ligation (BDL). Signaling activation of fibrogenesis in these two models will be now better studied. The role of kinin in liver metabolism was also studied in liver regeneration model in which we observed an apparent increase in glucose release by the liver after bolus injection of BK in the portal vein. It was reported in the literature in pathological conditions such as diabetes, increase in B1R expression in different tissues. Thus, we will verify the expression and possible role of B1R in the liver of animals undergoing experimental model of type I diabetes, type II and metabolic syndrome.In relation to the renin-angiotensin system, liver angiotensin II (AII) also has potent vasoconstrictor, and promotes glucose release. This metabolic effect may be due to its action to increase the concentration of intracellular calcium, which activates glycogen phosphorylase enzyme, but may still be related to the binding of AII to other liver receptors, eg adrenergic receptors. This hypothesis will be investigated using specific adrenergic agonists and antagonists. Previous results showed that the AII RHP in livers of rats with increased blood pressure (spontaneously hypertensive rats, SHR) is similar to normal rats. Although SHRs had decreased glycogen, the glucose release in the perfusion fluid induced by AII was similar. As we observed inconsistent results in the study of SHRs, other approaches are necessary, as experimental models of hypertension, to evaluate the metabolic action of AII on the liver. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
L.J.T. DE ARAÚJO; M.R. NAGAOKA; D.R. BORGES; M. KOUYOUMDJIAN. Participation of hepatic α/β-adrenoceptors and AT1 receptors in glucose release and portal hypertensive response induced by adrenaline or angiotensin II. Brazilian Journal of Medical and Biological Research, v. 51, n. 12, p. -, 2018.
DE ARAUJO, L. J. T.; NAGAOKA, M. R.; BORGES, D. R.; KOUYOUMDJIAN, M. Participation of hepatic alpha/beta-adrenoceptors and AT(1) receptors in glucose release and portal hypertensive response induced by adrenaline or angiotensin II. Brazilian Journal of Medical and Biological Research, v. 51, n. 12 2018. Web of Science Citations: 2.
KIMURA, DEBORA CONTE; NAGAOKA, MARCIA REGINA; BORGES, DURVAL ROSA; KOUYOUMDJIAN, MARIA. Angiotensin II or epinephrine hemodynamic and metabolic responses in the liver of L-NAME induced hypertension and spontaneous hypertensive rats. WORLD JOURNAL OF HEPATOLOGY, v. 9, n. 17, p. 781-790, JUN 18 2017. Web of Science Citations: 2.

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