Modelos de estudo de ativação do sistema renina angiotensina e seu papel na função cardíaca pós-isquêmica

• Ano de defesa: 2019
• Autor(a) principal: Jônathas Fernandes Queiroz de Almeida
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; ICB - DEPARTAMENTO DE FARMACOLOGIA; Programa de Pós-Graduação em Ciências Biológicas - Fisiologia e Farmacologia; UFMG
• Palavras-chave em Português: Sistema renina angiotensina (SRA); Função cardíaca; Ações biológicas
• Link de acesso: http://hdl.handle.net/1843/30478

The renin angiotensin system (RAS) plays a key role in cardiac function regulation. In the past years new peptides have been described and added in this system, making it even more complex. Alamandine was recently described and it already became an important target to study the RAS role in physiological and pathological events. In this work we evaluated the role of two RAS effectors, angiotensin II and alamandine, in two different animal models with marked activation of RAS. Our previous data showed that alamandine improved post-ischemic cardiac function in normotensive rats, therefore, in this work we continue this investigation by evaluating alamandine effects in a more challenging model, using TGR(mREN2)27 (mREN), a well stablish model of hypertension. Using Sprague-Dawley (SD) isolated hearts we found that alamandine presented cardioprotective effect on LVSP, dLVP, ±dP/dt, infarcted area and arrhythmia severity index. However, alamandine had no effects in mREN hearts, probably due the downregulation of MrgD receptor in this tissue. In our second experimental protocol, we used Fischer rats under two different diets for two weeks. First one was a regular diet with ad libitum ingestion (CT group), and second one was a severe food restricted diet with 60% of CT group ingestion (SFR). SFR rats showed electrolyte imbalance, 19% of body weight loss, plasmatic volume loss, cardiac atrophy, increased reperfusion arrhythmias, upregulation of AT1 receptor in left ventricle and increased Ang II pressor effect in mesenteric arteries. To evaluate long term effects of SFR, another group was submitted to 3 months of refeeding (SFR-rf). After refeeding, no differences were observed between SFR-rf and CT-rf groups. Together these data showed that RAS plays a key role in both models. In food restriction model, Ang II and AT1 receptor were the main effectors. Meanwhile, in hypertensive model, alamandine was unable to exercise its effects due MrgD downregulation.