Angiotensin-converting enzyme 2 alleviates liver fibrosis through the renin-angiotensin system

The present letter to the editor is related to the study titled‘Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells’.Angiotensin-converting enzyme 2 can alleviate liver fibrosis by regulating autophagy of hepatic stellate cells and affecting the renin-angiotensin system.

The Beneficial Effect of Renin-Angiotensin-Aldosterone System Blockade in Treatment of Hypertension, Resistant to Conventional Antihypertensives, in Patients on Maintenance Hemodialysis

Background: Hypertension (HTN) is present in up to 90% of end stage kidney disease (ESRD) patients irrespective of the etiology of their kidney disease. Moreover, it is an important modifiable risk factor for progression to ESRD and its overall cardiovascular morbidity and mortality. Objective: to evaluate, prospectively, the role of Renin-Angiotensin-Aldosterone System blockade (RAAS) in HTN, resistant to 3 conventional antihypertensives, in patients on maintenance hemodialysis (MHD). Patients and methods: A total of 52 such patients were treated with Ramipril and 5 with Losartan after intolerable cough/shortness of breath following Ramipril-use. None of the patients had fluid depletion, renal artery stenosis and primary endocrinopathy. The study group was compared to a matched control group of MHD patients with normal blood pressure following 3 drugs-combination therapies. Results: All patients, with resistant HTN, had significant activation of RAAS system prior to treatment compared to inactive one in the control group. In those with resistant HTN, control of HTN, was established within 2 weeks of therapy and was associated with suppression of the RAAS. Such therapy was associated with minor side effects. Conclusion: Our study has shown that RAAS blockade is safe and effective in controlling such resistant HTN in MHD patients.

Renin-angiotensin system in the central nervous system:focus on Huntington’s disease

The renin-angiotensin system(RAS)was originally conceived as a circulating hormonal system involved in the regulation of cardiovascular and renal homeostasis.With the discovery of local RAS components in diverse organs,including the brain,and related biologically active peptides.

Extracellular vesicles and angiotensin-converting enzyme 2 in COVID-19 disease

Extracellular vesicles(EVs)are membranous vesicular structures released from almost all eukaryotic cell types under different physiological or pathological conditions.Growing evidence demonstrates that EVs can serve as mediators of intercellular communication between donor and recipient cells or microorganism-infected and noninfected cells.Coronavirus disease 2019(COVID-19)disease is caused by infection of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)of host cells in the respiratory system and various extra-pulmonary tissue/organs,resulting in complications of multiple organ systems.As the cell surface receptor,angiotensin-converting enzyme 2(ACE2)mediates cellular entry of SARS-CoV-2 into the host cells in patients with COVID-19.Recent studies have found that ACE2 can be released with EVs,which have been shown to interfere with the entry of the virus into host cells and thus may be involved in COVID-19 pathophysiology.In addition,ACE2,neprilysin(NEP),and thimet oligopeptidase(TOP)are the key enzymes that regulate angiotensin metabolism by converting angiotensin II or angiotensin I to angiotensin 1-7,the latter of which has protective effects in counterbalancing the harmful effects of angiotensin II in COVID-19 disease.This review summarizes the recent research progress regarding EV-associated ACE2,NEP,and TOP and the perspectives of their potential involvement in the pathophysiology of COVID-19 disease.

Role of angiotensin receptor-neprilysin inhibitor in diabetic complications

Diabetes mellitus is a prevalent disorder with multi-system manifestations,causing a significant burden in terms of disability and deaths globally.Angio-tensin receptor-neprilysin inhibitor(ARNI)belongs to a class of medications for treating heart failure,with the benefits of reducing hospitalization rates and mortality.This review mainly focuses on the clinical and basic investigations related to ARNI and diabetic complications,discussing possible physiological and molecular mechanisms,with insights for future applications.

Biological function of miRNA-145-5p in angiotensin II induced renal inflammation

Objective:Chronic kidney disease(CKD)is a progressive disorder characterized by intricate structural and functional alterations in the kidneys,attributable to diverse causative factors.Notably,the therapeutic promise of miR-145-5p in addressing renal pathologies has been discerned.This investigation seeks to elucidate the functional role of miR-145-5p in injured kidneys by subjecting human glomerular mesangial cells(HGMCs)to stimulation with Angiotensin II(AngII).Materials and Methods:Cellular viability and the levels of inflammatory mediators were evaluated utilizing Cell Counting Kit-8(CCK-8),quantitative real-time polymerase chain reaction(qRT-PCR),and western blot methodologies,both in the presence of AngII incubation and in scenarios of miR-145p overexpression and downregulation.Furthermore,the cell cycle dynamics were elucidated through Fluorescence-activated Cell Sorting(FACS)analysis.Results:AngII incubation induced an upregulation of miR-145-5p and inflammatory factors including Intercellular Adhesion Molecule 1(ICAM-1),Interleukin 6(IL-6),Interleukin 8(IL-8),and Interleukin 1β(IL-1β).Additionally,it elevated the expression of Cyclin A2,Cyclin D1,and the G2/M cell cycle ratio.Conversely,inhibition of miR-145-5p heightened the levels of inflammatory factors and cell cycle regulators induced by AngII incubation.Reduced expression of miR-145-5p correlated with a downregulation of Interleukin 10(IL-10)expression,concurrently promoting HGMC proliferation under AngII stimulation.Moreover,ectopic miR-145-5p expression demonstrated a reduction in inflammatory factors,cell cyclin regulators,G2/M cell cycle ratio,and overall proliferation.Conclusion:MiR-145-5p exhibited inhibitory effects on the inflammatory response and proliferation induced by Angiotensin II in HGMCs,showcasing its potential as a therapeutic avenue for the treatment of kidney injury.

Impacts of angiotensin II on retinal artery changes in apolipoprotein E deficient mice

AIM:To investigate the impacts of angiotensin II(Ang II)on retinal artery changes in apolipoprotein E deficient(apoE^(-/-))mice.METHODS:ApoE^(-/-)male mice were infused by minipumps with Ang II at 1000 ng/kg·min(Ang II group)or saline(control group)for 28d.They were underwent ophthalmic fundus examination on day 0,14,and 28 of infusion.Histopathologic examination,ribonucleic acid(RNA)sequencing and local Ang II measurement of retinas were conducted.RESULTS:Ophthalmic fundus examination showed Ang II infusion promoted the formation of retinal arterial aneurysm-like lesions on day 28.Optical coherence tomography revealed the ganglion cell and inner plexiform layer(GCIPL)thickness in the control group was significantly thinner than that in Ang II group(P<0.001).Hematoxylin-eosin staining demonstrated diffused swelling of GCIPL layer and its disordered structure in Ang II group.Transmission electron microscopy showed Ang II infusion caused aggravation of atherosclerotic lesions,including increased swelling,roughness,disorganization of the retinal vasculature,and vacuoles formation.RNA-sequencing and gene ontology enrichment analysis demonstrated that the structure and function of cellular membrane might be disturbed and visual function might be compromised by Ang II.The local level of Ang II was higher in Ang II infusion group but did not show significant differences compared to the control group(P=0.086).CONCLUSION:Ang II infusion promotes the formation of retinal arterial aneurysm-like lesions in apoE^(-/-)mice,causing aggravation of atherosclerotic lesions,more severe disorganization of the retinal vasculature and disturbance of the cellular membrane.

Influence of Angiotensin II on α1-Adrenergic Receptors Function in Rat Aorta and Expression in Vascular Smooth Muscle Cells

Angiotensin II (Ang II) is the main mediator of the Renin-Angiotensin-System acting on AT1 and other AT receptors. It is regarded as a pleiotropic agent that induces many actions, including functioning as a growth factor, and as a contractile hormone, among others. The aim of this work was to examine the impact of Ang II on the expression and function of α1-adrenergic receptors (α1-ARs) in cultured rat aorta, and aorta-derived smooth muscle cells. Isolated Wistar rat aorta was incubated for 24 h in DMEM at 37˚C, then subjected to isometric tension and to the action of added norepinephrine, in concentration-response curves. Ang II was added (1 × 10−5 M), and in some experiments, 5-Methylurapidil (α1A-AR antagonist), AH11110A (α1B-AR antagonist), or BMY-7378 (α1D-AR antagonist), were used to identify the α1-AR involved in the response. Desensitization of the contractile response to norepinephrine was observed due to incubation time, and by the Ang II action. α1D-AR was protected from desensitization by BMY-7378;while RS-100329 and prazosin partially mitigated desensitization. In another set of experiments, isolated aorta-derived smooth muscle cells were exposed to Ang II and α1-ARs proteins were evaluated. α1D-AR increased at 30 and 60 min post Ang II exposure, the α1A-AR diminished from 1 to 4 h, while α1B-AR remained unchanged over 24 h of Ang II exposure. Ang II induced an increase of α1D-AR at short times, and BMY-7378 protected α1D-AR from desensitization.

Renin-angiotensin system in the pathogenesis of liver fibrosis

Hepatic fibrosis is considered a common response to many chronic hepatic injuries.It is a multifunctional process that involves several cell types,cytokines,chemokines and growth factors leading to a disruption of homeostatic mechanisms that maintain the liver ecosystem.In spite of many studies regarding the development of fibrosis,the understanding of the pathogenesis remains obscure.The hepatic tissue remodeling process is highly complex,resulting from the balance between collagen degradation and synthesis.Among the many mediators that take part in this process,the components of the Renin angiotensin system(RAS) have progressively assumed an important role.Angiotensin(Ang)□acts as a profibrotic mediator and Ang-(1-7),the newly recognized RAS component,appears to exert a counter-regulatory role in liver tissue.We briefly review the liver fibrosis process and current aspects of the RAS.This review also aims to discuss some experimental evidence regarding the participation of RAS mediators in the pathogenesis of liver fibrosis,focusing on the putative role of the ACE2-Ang-(1-7)-Mas receptor axis.

Meta-analysis of effects of obstructive sleep apnea on the renin-angiotensinaldosterone system

BackgroundObstructive 睡觉呼吸暂停(OSA ) 是抵抗高血压的最普通的原因，它被建议了源于 renin-angiotensin-aldosterone 系统(RAAS ) 的激活。我们分析元 RAAS components.MethodsFull 文章研究的血浆层次上的 OSA 的效果在与 OSA 在成年人分析至少一个 RAAS 部件的 fasting 血浆层次与或没有高血压的 MEDLINE 和 EMBASE 上出版了。OSA 作为一个呼吸暂停呼吸过慢过浅索引或呼吸骚乱索引 ≥ 被诊断；5。学习质量用纽卡斯尔渥太华规模被评估，并且异质用 I 2 统计数值被估计。从单个研究的结果用反的变化被综合并且分享了使用一个随机效果的模型。亚群分析，敏感分析，和元回归被执行，并且出版偏爱的风险是包括的 assessed.ResultsThe 元分析 13 研究， 10 在高血压蛋白原酶上报导了结果( n = 470 个案例和控制)， 7 在血管收缩素 II 上( AngII ， n = 384 )，并且 9 在醛固酮上( n = 439 )。AngII 层次比在控制在 OSA 是显著地更高的[吝啬的差别 = 3.39 ng/L， 95% CI：2.00-4.79， P <；0.00001 ] 当醛固酮层次比 OSA 然而并非与高血压在有高血压的 OSA 是显著地更高的时(吝啬的差别 = 1.32 ng/dL， 95% CI：0.58-2.07， P = 0.0005 ) 。所有研究的元分析没在醛固酮在之间建议重要差别 OSA 和控制，而是一个重要分享的平均数 1.35 ng/mL 的差别(95% CI：0.88-1.82， P <；0.00001 ) 出现在排除一小样品的研究以后。出版偏爱的重要风险都没在所有包括的 studies.ConclusionsOSA 之中被检测与更高的 AngII 和醛固酮层次被联系，特别在高血压的病人。OSA 可以引起高血压，至少部分地，由刺激 RAAS 活动。

What have we learned about the kallikrein-kinin and renin-angiotensin systems in neurological disorders?

The kallikrein-kinin system(KKS) is an intricate endogenous pathway involved in several physiological and pathological cascades in the brain. Due to the pathological effects of kinins in blood vessels and tissues, their formation and degradation are tightly controlled. Their components have been related to several central nervous system diseases such as stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy and others. Bradykinin and its receptors(B1R and B2R) may have a role in the pathophysiology of certain central nervous system diseases. It has been suggested that kinin B1R is up-regulated in pathological conditions and has a neurodegenerative pattern, while kinin B2R is constitutive and can act as a neuroprotective factor in many neurological conditions. The renin angiotensin system(RAS) is an important blood pressure regulator and controls both sodium and water intake. AngⅡ is a potent vasoconstrictor molecule and angiotensin converting enzyme is the major enzyme responsible for its release. AngⅡ acts mainly on the AT1 receptor, with involvement in several systemic and neurological disorders. Brain RAS has been associated with physiological pathways, but is also associated with brain disorders. This review describes topics relating to the involvement of both systems in several forms of brain dysfunction and indicates components of the KKS and RAS that have been used as targets in several pharmacological approaches.

Renin-angiotensin system in the kidney: What is new?

The renin-angiotensin system(RAS)has been known for more than a century as a cascade that regulates body fluid balance and blood pressure.AngiotensinⅡ(AngⅡ)has many functions in different tissues;however it is on the kidney that this peptide exerts its main functions.New enzymes,alternative routes for AngⅡformation or even active AngⅡ-derived peptides have now been described acting on AngⅡAT1or AT2receptors,or in receptors which have recently been cloned,such as Mas and AT4.Another interesting observation was that old members of the RAS,such as angiotensin converting enzyme(ACE),renin and prorenin,well known by its enzymatic activity,can also activate intracellular signaling pathways,acting as an outside-in signal transduction molecule or on the renin/(Pro)renin receptor.Moreover,the endocrine RAS,now is also known to have paracrine,autocrine and intracrine action ondifferent tissues,expressing necessary components for local AngⅡformation.This in situ formation,especially in the kidney,increases AngⅡlevels to regulate blood pressure and renal functions.These discoveries,such as the ACE2/Ang-(1-7)/Mas axis and its antangonistic effect rather than classical deleterious AngⅡeffects,improves the development of new drugs for treating hypertension and cardiovascular diseases.

Prevention of atrial fibrillation with renin-angiotensin system inhibitors on essential hypertensive patients:a meta-analysis of randomized controlled trials

We aimed to investigate the effectiveness and safety of angiotensin-converting enzyme inhibitors （ACEIs） or angiotensin Ⅱ receptor blockers （ARBs） on preventing atrial fibrillation in essential hypertensive patients. Systematic literature retrieval was carried out to obtain randomized controlled trials on the effects of ACEI/ ARBs on essential hypertensive patients before December, 2013. Data extraction and quality evaluation were performed. Meta-analysis was performed by Review Manager 5.2.3. Ten high quality studies （11 articles） with a total of 42,892 patients （20,491 patients in the ACEI/ARBs group and 22,401 patients in the β-blocker or the calcium antagonist group） met the inclusion criteria and were included in the meta-analysis. The results showed that ACEI/ARBs reduced the incidence of atrial fibrillation （AF） recurrence compared to calcium antagonists （RR=0.48; 95%CI, 0.40-0.58; P〈0.00001） or β-blockers （RR=0.39; 95%CI, 0.20-0.74; P=0.005） in long-term follow-up, respectively. Furthermore, ACEI/ARBs reduced the incidence of conges- tive heart failure （RR=0.86; 95%CI, 0.77-0.96; P=0.007）. However, no significant effects were observed on the incidence of new AF, cardiac death, myocardial infarction, and stroke. Our results suggest that ACEI/ ARBs may reduce the incidence of AF recurrence and congestive heart failure, with fewer serious adverse effects.

Effects of Yinchenhao Decoction on Self-regulation of Renin-angiotensin System by Targeting Angiotensin Converting Enzyme 2 in Bile Duct-ligated Rat Liver

Summary： In order to investigate whether Yinchenhao decoction （YCHD） attenuates hepatic fibro- genesis in the bile duct ligation （BDL） model via recovering and restoring the self-regulation and bal- ance of the renin-angiotensin system （RAS）, 33 specific-pathogen-free （SPF） male Sprague-Dawley rats with common BDL and scission were randomly divided into five groups as follows： G1, the sham group （n=4）; G2, BDL 7-day group （n=5）; G3, BDL＋YCHD 430 mg/mL （n=8）; G4, BDL＋losartan 0.65 mg/mL （ARB group, n=8）; G5, model group （BDL without any treatment, n=8）. YCHD and losartan （10 mL.kgl.day-1） were given by gastric gavage for 16 days following BDL in G3 and G4 groups, respec- tively. The effect of YCHD on liver fibrosis and the detailed molecular mechanisms were assessed by liver function including total bilirubin （TBIL）, direct bilirubin （DBIL）, indirect bilirubin （IDBIL）, alanine aminotransferase （ALT）, and aspartate aminotransferase （AST）. Histological changes were ob-. served by transmission electron microscopy （TEM） and Masson trichrome staining. Western blotting was used to detect the protein expression level of the renin-angiotensin system （RAS） components in- cluding angiotensin converting enzyme （ACE）, angiotensin II type 1 receptor （AT1R）, ACE2, angio- tensin II （Ang II） as well as transforming growth factor 131 （TGF131）. The experimental data were ana- lyzed by principle component analytical method of pattern recognition. The results showed that bio- chemically, serum TBIL, DBIL, IDBIL, ALT and AST levels were markedly increased following BDL as compared with the sham group （P〈0.05）. Serum TBIL, IDBIL and DBIL levels in G3 group were dramatically decreased as compared with G5 and G4 groups （P〈0.05）. Serum AST level in G3 was sig- nificantly lowered than in G5 group （P〈0.05）, but there was no significant difference in ALT among G3, G4 and G5 groups （P〉0.05）. Histologically, livers in G3 group showed less hepatocytes necrosis, less bile duct hyperplasia and less collagen formation than in G4 and G5 groups. The protein expression lev- els of ACE2, ACE, Ang II, AT1R and TGF131 in G2, G3 and G4 groups were significantly higher than in sham group （P〈0.05）, and lower than in G5 group （P〈0.05）. However, the differences among G2, G3 and G4 groups were not significant （P〉0.05）. ACE2 protein expression in G3 group was significantly higher than in G2 group （P〈0.05） and there was no significant difference in comparison with G4 group （P〉0.05）. Moreover, the protein expression of TGF131 in G3 group was significantly lower than in G5 and G4 groups （P〈0.05）. Our findings suggest that the antifibrotic effects of YCHD may be associated with the decreased classical RAS pathway components and TGFI31 downexpression so as to recover and rebuild self-regulation of the RAS by elevating the protein expression of ACE2.

Systematic review: Renin-angiotensin system inhibitors in chemoprevention of hepatocellular carcinoma

BACKGROUND Neoangiogenesis is one of the key pathogenetic mechanisms in hepatocellular carcinoma (HCC). Modulation of the renin-angiotensin system (RAS) by angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) seems to be a possible adjuvant therapy for HCC, due to the antiangiogenic and anti-fibrogenic activity of these drugs. AIM To elucidate the role of ARBs and ACE-Is in HCC. METHODS We performed an electronic search of the literature using the most accessed online databases (PubMed, Cochrane library, Scopus and Web of Science), entering the query terms "angiotensin-converting enzyme inhibitors" OR "ACE inhibitors" OR "ACE-I" AND "hepatocarcinoma*" OR "hepatocellular carcinoma;moreover "angiotensin II type 1 receptor blockers" OR "ARBs" AND "hepatocarcinoma*" OR "hepatocellular carcinoma". Eligibility criteria were:(1) prospective or retrospective clinical studies;(2) epidemiological studies;and (3) experimental studies conducted in vivo or in vitro. Abstracts, conference papers, and reviews were excluded a priori. We limited our literature search to articles published in English, in peer-reviewed journals.RESULTS Thirty-one studies were selected. Three interventional studies showed that ACEIs had a significant protective effect on HCC recurrence only when used in combination with vitamin K or branched chain aminoacids, without a significant increase in overall survival. Of six retrospective observational studies, mainly focused on overall survival, only one demonstrated a prolonged survival in the ACE-Is group, whereas the two that also evaluated tumor recurrence showed conflicting results. All experimental studies displayed beneficial effects of RAS inhibitors on hepatocarcinogenesis. Numerous experimental studies, conducted either on animals and cell cultures, demonstrated the anti-angiogenetic and antifibrotic effect of ACE-Is and ARBs, thanks to the suppression of some cytokines such as vascular endothelial growth factor, hypoxia-inducible factor-1a, transforming growth factor-beta and tumor necrosis factor alpha. All or parts of these mechanisms were demonstrated in rodents developing fewer HCC and preneoplastic lesions after receiving such drugs. CONCLUSION In humans, RAS inhibitors - alone or in combination - significantly suppressed the cumulative HCC recurrence, without prolonging patient survival, but some limitations intrinsic to these studies prompt further investigations.

Time to re-evaluate effects of renin-angiotensin system inhibitors on renal and cardiovascular outcomes in diabetic nephropathy

The use of renin-angiotensin system(RAS) inhibitors, such angiotensin converting enzyme inhibitors/angiotensin-Ⅱreceptor blockers, to slow progression of chronic kidney disease(CKD) in a large group dominated by elderly people in the real world is not supported by available evidence. Large-scale clinical trials had many faults,among them a lack of focus on the elderly. However,it would be difficult to conduct clinical trials of a similar scale in elderly CKD patients. Besides, progression ofkidney disease is often slow in elderly persons, and the vast majority of older adults with CKD will die before reaching end stage renal disease. Moreover, since it is not clear that progression of kidney disease, and even of proteinuric diabetic nephropathy, is not inhibited through the use of RAS inhibitors, the most patientcentric goal of therapy for many elderly individuals should be individualized.

Inhibition of the Renin-Angiotensin System and Cardiovascular Mortality in Chronic Hemodialysis Patients

INTRODUCTION: Since the outcomes associated with the use of renin-angiotensin-system inhibitors (RASi) by hemodialysis (HD) patients are not fully known, we investigated their effect on the cardiovascular mortality of chronic HD patients. METHODS: Data from 388 HD patients (237 men and 151 women) who were routinely treated for at least 6 months were analyzed. Treatment with a RASi was the major predictor variable. The main outcome measure was cardiovascular mortality. Cox regression analysis was used to assess for the use of RASi and risk of death. RESULTS: Hypertension was diagnosed in 320 patients (82.5%), and 197 (50.8%) of them were treated with a RASi (treated group) and 191 (49.2%) were not (untreated group). The treated group had a higher prevalence of hypertension, history of congestive heart failure, and presence of ST-T changes. Kaplan-Meier analysis revealed a reduction in risk of cardiovascular death in the treated group during the follow-up period (fig. 2;log-rank: p=0.0379). The multivariate analysis showed that treatment with a RASi was also independently associated with reduced cardiovascular mortality (hazard ratio= 0.184;p=0.0161). CONCLUSIONS: The results of this study suggest a possible association between the treatment with RASi and reduced risk of cardiovascular mortality, independent of their effect of lowering blood pressure.

Renin-Angiotensin System and Thrombosis

Considerable evidence has accumulated to support the concept that the effects of the renin-agniotensin system can be mediated through two modes: endocrine and paracrine modes.

Changes of Renin-angiotensin-aldoster one System and Its Clinical Significance in Chronic Hepatitis B Patients

Plasma angiotensin-Ⅱ(AT-Ⅱ)and aldcoterone (ALD) were determined in 33 cases withchronic hepatitis B. During the stable stage of chronic persistent hepatitis (CPH) and chronic active hepaatitis (CAH), the concentration of plasma ALD was over two times higher than its normal range, whilethe concentration of plasma AT-Ⅱ was different from normal values. In patients with liver cirrhosiswithout ascites, plasma AT-Ⅱ was normal, while plasma ALD was also over two times above the normallevel. In patients with ascites the concentrations of both plasma AT-Ⅱ and ALD were over five timeshigher than normal. In 23 cases with chronic hepatitis B, furasemide stimulation test provoked a markedelevation of plasma AT-Ⅱ level.These results shoewd that ascies was associated withh both hypovolemiaand excitation of renin-angiotensin-aldbsterone spstem. Therefore, in order to reduce the side effects.potent diuretics should be used only in appropriate doses for patients with end stage of liver cirrhosis.

Renin-angiotensin system blockade: Effect on renal mRNA expression in 5/6 nephrectomized rats

The aim of this study was to determinate the gene expression levels of angiotensinogen, angiotensin converting enzyme, renin, (pro)renin receptor, and the final rennin-angiotensin system (RAS) products Angiotensin (Ang) II and Ang 1-7 inthe remnant kidney of 5/6 nephrectomized rats and its response to RAS pharmacological blockade. Male Wistar rats were divided into five groups: sham operated (SO), 5/6 nephrectomized (NFX), NFX + captopril (50 mg/ kg/day), NFX + losartan (10 mg/kg/day), and NFX + aliskiren (10 mg/kg/day). Animals were followed up for 60 days and protein urine excretion was measured. Systolic blood pressure, renal tissue RAS mRNA expression levels, plasma Ang II, and plasma Ang 1-7 were evaluated at day 60 after nephrectomy. Blood pressure and urine protein were increased after 5/6 nephrectomy. Ang II levels were increased 9.4 fold, whereas Ang 1-7 decreased 72.9% in NFX animals compared with SO rats. 5/6 nephrectomy increased renal angiotensinogen and (pro)renin receptor mRNA expression but down-regulated renin mRNA expression. RAS blockade restored the systolic blood pressure to normal values and slowed down urinary protein excretion, and also prevented changes in Ang II and Ang 1-7. RAS blockade reduced (pro)renin receptor, ACE, and AGT mRNA expression in the remnant kidney. However, renin mRNA expression increased compared with NFX rats. In conclusion these results suggest that inhibition of Ang II synthesis by RAS blockade is associated with renal regulation of RAS mRNA expression and this may be through a mechanism related with the Ang II/Ang 1-7 balance.