Exercise induces renin-angiotensin system unbalance and high collagen expression in the heart of Mas-deficient mice.

The renin-angiotensin system (RAS) is involved in the cardiac and vascular remodeling associated with cardiovascular diseases. Angiotensin (Ang) II/AT(1) axis is known to promote cardiac hypertrophy and collagen deposition. In contrast, Ang-(1-7)/Mas axis opposes Ang II effects in the heart producing anti-trophic and anti-fibrotic effects. Exercise training is known to induce cardiac remodeling with physiological hypertrophy without fibrosis. We hypothesize that cardiac remodeling induced by chronic exercise depends on the action of Ang-(1-7)/Mas axis. Thus, we evaluated the effect of exercise training on collagen deposition and RAS components in the heart of FVB/N mice lacking Mas receptor (Mas-KO). Male wild-type and Mas-KO mice were subjected to a moderate-intense swimming exercise training for 6 weeks. The left ventricle (LV) of the animals was sectioned and submitted to qRT-PCR and histological analysis. Circulating and tissue angiotensin peptides were measured by RIA. Sedentary Mas-KO presented a higher circulating Ang II/Ang-(1-7) ratio and an increased ACE2 expression in the LV. Physical training induced in Mas-KO and WT a similar cardiac hypertrophy accompanied by a pronounced increase in collagen I and III mRNA expression. Trained Mas-KO and trained WT presented increased Ang-(1-7) in the blood. However, only in trained-WT there was an increase in Ang-(1-7) in the LV. In summary, we showed that deletion of Mas in FVB/N mice produced an unbalance in RAS equilibrium increasing Ang II/AT(1) arm and inducing deleterious cardiac effects as deposition of extracellular matrix proteins. These data indicate that Ang-(1-7)/Mas axis is an important counter-regulatory mechanism in physical training mediate cardiac adaptations.

Guimarães GG ，Santos SH ，Oliveira ML ，Pimenta-Velloso EP ，Motta DF ，Martins AS ，Alenina N ，Bader M ，Santos RA ，Campagnole-Santos MJ ... -  《-》

Physical Exercise and ACE2-Angiotensin-(1-7)-Mas Receptor Axis of the Renin Angiotensin System.

Many physiological responses of the Renin Angiotensin System (RAS) are associated with two opposite pathways: (1) a classical one formed by angiotensin-converting enzyme (ACE), Angiotensin II (Ang II) and Angiotensin type 1 (AT1) receptor, which is associated to vasoconstriction, cell proliferation, organ hypertrophy, sodium retention and aldosterone release and (2) a counter-regulatory or vasodilator pathway comprising angiotensin-converting enzyme 2 (ACE2), Angiotensin-(1-7) [Ang-(1-7)] and Mas receptor, which is involved in vasodilation, antiproliferation, anti-hypertrophy, cardioprotective and renoprotective actions. This review aimed to bring up-to-date on the interactions between physical exercise and the vasodilator axis of the RAS (ACE2-Ang-(1-7)-Mas receptor axis). We also investigated the relation of acute and chronic exercise with blood pressure regulation and components of the vasodilator axis of the RAS. We searched studies with animal models and humans in PUBMED, LILACS and IBECS. Experimental studies showed that physical training can stimulate ACE2-Ang-(1-7)-Mas receptor axis in parallel with the inhibition of ACE-Ang II-AT1 receptor pathway. However, up to now, the interaction between the counter-regulatory RAS axis and physical training is not investigated in humans. The activation of ACE2-Ang-(1-7)-Mas receptor axis may have a role in the beneficial effects of physical training in experimental models. Further studies with humans are necessary.

Nunes-Silva A ，Rocha GC ，Magalhaes DM ，Vaz LN ，Salviano de Faria MH ，Simoes E Silva AC ... -  《-》

High-intensity interval training has beneficial effects on cardiac remodeling through local renin-angiotensin system modulation in mice fed high-fat or high-fructose diets.

HIIT (high-intensity interval training) has the potential to reduce cardiometabolic risk factors, but the effects on cardiac remodeling and local RAS (renin-angiotensin system) in mice fed high-fat or high-fructose diets still need to be fully addressed. Sixty male C57BL/6 mice (12weeks old) were randomly divided into three groups, control (C), High-fat (HF), or High-fructose diet (HRU) and were monitored for eight weeks before being submitted to the HIIT. Each group was randomly assigned to 2 subgroups, one subgroup was started on a 12-week HIIT protocol (T=trained group), while the other subgroup remained non-exercised (NT=not-trained group). HIIT reduced BM and systolic blood pressure in high-fat groups, while enhanced insulin sensitivity after high-fat or high-fructose intake. Moreover, HIIT reduced left ventricular hypertrophy in HF-T and HFRU-T. Notably, HIIT modulated key factors in the local left ventricular renin-angiotensin-system (RAS): reduced protein expression of renin, ACE (Angiotensin-converting enzyme), and (Angiotensin type 2 receptor) AT2R in HF-T and HFRU-T groups but reduced (Angiotensin type 1 receptor) AT1R protein expression only in the high-fat trained group. HIIT modulated ACE2/Ang (1-7)/Mas receptor axis. ACE2 mRNA gene expression was enhanced in HF-T and HFRU-T groups, complying with elevated Mas (Mas proto-oncogene, G protein-coupled receptor) receptor mRNA gene expression after HIIT. This study shows the effectiveness of HIIT sessions in producing improvements in insulin sensitivity and mitigating LV hypertrophy, though hypertension was controlled only in the high-fat-fed submitted to HIIT protocol. Local RAS system in the heart mediates these findings and receptor MAS seems to play a pivotal role when it comes to the amelioration of cardiac structural and functional remodeling due to HIIT.

de Oliveira Sá G ，Dos Santos Neves V ，de Oliveira Fraga SR ，Souza-Mello V ，Barbosa-da-Silva S ... -  《-》

Lifetime overproduction of circulating Angiotensin-(1-7) attenuates deoxycorticosterone acetate-salt hypertension-induced cardiac dysfunction and remodeling.

Santiago NM ，Guimarães PS ，Sirvente RA ，Oliveira LA ，Irigoyen MC ，Santos RA ，Campagnole-Santos MJ ... -  《-》

Cardiac hypertrophy in mice submitted to a swimming protocol: influence of training volume and intensity on myocardial renin-angiotensin system.

Soares DDS ，Pinto GH ，Lopes A ，Caetano DSL ，Nascimento TG ，Andrades ME ，Clausell N ，Rohde LEP ，Leitão SAT ，Biolo A ... -  《-》