Angiotensin type 2 receptor null mice express reduced levels of renal angiotensin II type 2 receptor/angiotensin (1-7)/Mas receptor and exhibit greater high-fat diet-induced kidney injury.

Renin-angiotensin system (RAS) components exert diverse physiological functions and have been sub-grouped into deleterious angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/angiotensin type 1 receptor (AT1R) and protective ACE2/angiotensin (1-7) (Ang-(1-7))/Mas receptor (MasR) axes. We have reported that chronic activation of angiotensin type 2 receptor (AT2R) alters RAS components and provides protection against obesity-related kidney injury. We utilized AT2R knockout (AT2KO) mice in this study and evaluated the renal expression of various RAS components and examined the renal injury after placing these mice on high fat diet (HFD) for 16 weeks. The cortical ACE2 activity and MasR expression were significantly decreased in AT2KO mice compared to wild type (WT) mice. LC/MS analysis revealed an increase in renal Ang II levels and a decrease in Ang-(1-7) levels in AT2KO mice. Cortical expression of ACE and AT1R was increased but renin activity remained unchanged in AT2KO compared with WT mice. WT mice fed HFD exhibited increased systolic blood pressure, higher indices of kidney injury, mesangial matrix expansion score, and microalbuminuria, which were further increased in AT2KO mice. This study suggests that deletion of AT2R decreases the expression of the beneficial ACE2/Ang-(1-7)/MasR and increases the deleterious ACE/Ang II/AT1R axis of the renal RAS in mice. Further, AT2KO mice are more susceptible to HFD-induced renal injury.

Ali Q ，Dhande I ，Samuel P ，Hussain T ... -  《-》

High Na intake increases renal angiotensin II levels and reduces expression of the ACE2-AT(2)R-MasR axis in obese Zucker rats.

Samuel P ，Ali Q ，Sabuhi R ，Wu Y ，Hussain T ... -  《-》

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 ... -  《-》

Sini decoction alleviates E. coli induced acute lung injury in mice via equilibrating ACE-AngII-AT1R and ACE2-Ang-(1-7)-Mas axis.

Acute respiratory distress syndrome (ARDS), one of the serious form of acute lung injury (ALI), is the primary cause of death in patients with ALI. Sini decoction (SND) is a widely used Traditional Chinese Medicine (TCM). However, the application of SND in ALI is rarely reported. Previous studies have found that renin-angiotensin-aldosterone system (RAAS) played vital and bidirectional roles in ALI. Therefore, the aim of the present study was to investigate protective effect of SND on ALI model induced by E. coli, as well as to further explore relations between RAAS and SND. The ALI model was evaluated by morphological observations and biochemical assays. The expression levels of angiotensin converting enzyme (ACE), Angiotensin II type 1 receptor (AT1R) and angiotensin converting enzyme 2 (ACE2) were examined by Western blotting. The expression levels of angiotensinII (AngII) and angiotensin-(1-7) (Ang-(1-7)) were measured through ELISA. MasR, IL-6, IL-1β and TNFα were all measured using qRT-PCR. SND significantly ameliorated E. coli-induced ALI, including reducing inflammatory factors in lung tissue and the activity of MPO in serum. Furthermore, SND could obviously decrease the expression of ACE, AngII and AT1R, which were induced by E. coli. On the other hand, SND could markedly activate ACE2-Ang-(1-7)-Mas pathway. In this paper, we demonstrated that SND alleviates E. coli induced acute lung injury in mice via equilibrating ACE-AngII-AT1R and ACE2-Ang-(1-7)-Mas axis.

Liu J ，Chen Q ，Liu S ，Yang X ，Zhang Y ，Huang F ... -  《-》

Chronic AT2 receptor activation increases renal ACE2 activity, attenuates AT1 receptor function and blood pressure in obese Zucker rats.

Ali Q ，Wu Y ，Hussain T 《-》