Association between renin-angiotensin system inhibitor and the risk of CMV pneumonia:a Mendelian randomization study

Background:Cytomegalovirus(CMV)reactivation is linked to a high mortality rate,especially among the elderly.Prior research suggests that renin-angiotensin system(RAS)inhibitors may influence both the onset and prognosis of pneumonia.This study aims to examine the causal relationship between RAS inhibitor use and the risk of CMV pneumonia using Mendelian randomization(MR)analysis.Methods:We conducted an analysis using data from two genome-wide association studies(GWAS)involving individuals of European ancestry.This dataset included individuals treated with RAS inhibitors and those with CMV pneumonia.We assessed the relationship between RAS inhibitor use and CMV pneumonia risk using the inverse variance weighted(IVW)method.The results were further evaluated for pleiotropy,heterogeneity,and robustness.Results:The Mendelian randomization(MR)analysis revealed a causal relationship between RAS inhibitor use and an increased risk of CMV pneumonia(IVW:odds ratio[OR]=2.73;95%confidence interval[CI]=1.11-6.73;P=0.028).Conclusions:Our finding indicate a positive causal relationship between the use of RAS inhibitors and the onset of CMV pneumonia.

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 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） II 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.

Role of the renin angiotensin system in diabetic nephropathy

Diabetic nephropathy has been the cause of lot of morbidity and mortality in the diabetic population. The renin angiotensin system (RAS) is considered to be involved in most of the pathological processes that result in diabetic nephropathy. This system has various subsystems which contribute to the disease pathology. One of these involves angiotensin II (Ang II) which shows increased activity during diabetic nephropathy. This causes hypertrophy of various renal cells and has a pressor effect on arteriolar smooth muscle resulting in increased vascular pressure. Ang II also induces inflammation, apoptosis, cell growth, migration and differentiation. Monocyte chemoattractant protein-1 production responsible for renal fibrosis is also regulated by RAS. Polymorphism of angiotensin converting enzyme (ACE) and Angiotensinogen has been shown to have effects on RAS. Available treatment modalities have proven effective in controlling the progression of nephropathy. Various drugs (based on antagonism of RAS) are currently in the market and others are still under trial. Amongst the approved drugs, ACE inhibitors and angiotensin receptor blockers (ARBs) are widely used in clinical practice. ARBs are shown to be superior to ACE inhibitors in terms of reducing proteinuria but the combined role of ARBs with ACE inhibitors in diabetic nephropathy is under debate.

Renin angiotensin system in liver diseases: Friend or foe?

In the last three decades,the understanding of the renin angiotensin system(RAS)has been changed by the discoveries of functional local systems,novel biologically active peptides,additional specific receptors,alternative pathways of angiotensin(Ang)?Ⅱ?generation,and new roles for enzymes and precursor components other than those in Ang?Ⅱ?synthesis.In this regard,the discovery that Ang-(1-7)opposes the pressor,proliferative,pro-fibrotic,and pro-inflammatory effects mediated by Ang?Ⅱ?has contributed to the realization that the RAS is composed of two axes.The first axis consists of the angiotensin-converting enzyme(ACE),with Ang?Ⅱ?as the end product,and the angiotensin type 1(AT1)receptor as the main effector mediating the biological actions of Ang?Ⅱ.The second axis results from ACE2-mediated hydrolysis of Ang?Ⅱ,leading to the production of Ang-(1-7),with the Mas receptor as the main effector conveying the vasodilatory,antiproliferative,anti-fibrotic,and anti-inflammatory effects of Ang-(1-7).Experimental and clinical studies have shown that both axes of the RAS may take part in the pathogenesis of liver diseases.In this manuscript,we summarize the current evidence regarding the role of RAS in hepatic cirrhosis and its complications,including hemodynamic changes and hepatorenal syndrome.The therapeutic potential of the modulation of RAS molecules in liver diseases is also discussed.

Inflammation, oxidative stress and renin angiotensin system in atherosclerosis

Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin Ⅱ(Ang Ⅱ) and a decrease in nitric oxide. The renin-angiotensin system(RAS), and its primary mediator Ang Ⅱ, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors(angiotensin-converting enzyme inhibitors)], Ang Ⅱ receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in Apo E-deficient atherosclerotic mice.

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.

Therapeutic potential of targeting the renin angiotensin system in portal hypertension

Portal hypertension is responsible for the bulk of the morbidity and mortality in patients with cirrhosis.Drug therapy to reduce portal pressure involves targeting two vascular beds.The first approach is to reduce intra hepatic vascular tone induced by the activity of powerful vasocontrictors such as angiotensin Ⅱ,endothelin-1 and the sympathetic system and mediated via contraction of perisinusoidal myofibroblasts and pervascular smooth muscle cells.The second approach is to reduce mesenteric and portal blood flow.Non-selective b-blockers are widely used and have been shown to prolong patient survival and reduce oesophageal variceal bleeding in advanced cirrhosis.However many patients are unable to tolerate these drugs and they are ineffective in a significant proportion of patients.Unfortunately there are no other drug therapies that have proven efficacy in the treatment of portal hypertension and prevention of variceal bleeding.This review briefly outlines current therapeutic approaches to themanagement of portal hypertension,and the evidence supporting the role of the renin angiotensin system(RAS) and the use of RAS blockers in this condition.It will also outline recent advances in RAS research that could lead to the development of new treatments focusing in particular on the recently discovered "alternate axis" of the RAS.

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.

Effect of propranolol on the splanchnic and peripheral renin angiotensin system in cirrhotic patients

AIM:To evaluate the effect of β-blockade on angiotensins in the splanchnic and peripheral circulation of cirrhotic patients and also to compare hemodynamic parameters during liver transplantation according to propranolol pre-treatment or not. METHODS:Patients were allocated into two groups:outpatients with advanced liver disease(LD) and during liver transplantation(LT). Both groups were subdivided according to treatment with propranolol or not. Plasma was collected through peripheral venipuncture to determine plasma renin activity(PRA),Angiotensin(Ang) Ⅰ,Ang Ⅱ,and Ang-(1-7) levels by radioimmunoassay in LD group. During liver transplantation,hemodynamic parameters were determined and blood samples were obtained from the portal vein to measure renin angiotensin system(RAS) components.RESULTS:PRA,Ang Ⅰ,Ang Ⅱ and Ang-(1-7) were signifi cantly lower in the portal vein and periphery in all subgroups treated with propranolol as compared to non-treated. The relationships between Ang-(1-7) and Ang Ⅰ levels and between Ang Ⅱ and Ang Ⅰ were significantly increased in LD group receiving propranolol. The ratio between Ang-(1-7) and Ang Ⅱ remained unchanged in splanchnic and peripheral circulation in patients under β-blockade,whereas the relationship between Ang Ⅱ and Ang Ⅰ was significantly increased in splanchnic circulation of LT patients treated with propranolol. During liver transplantation,cardiac output and index as well systemic vascular resistance and index were reduced in propranolol-treated subgroup. CONCLUSION:In LD group,propranolol treatment reduced RAS mediators,but did not change the ratio between Ang-(1-7) and Ang Ⅱ in splanchnic and peripheral circulation. Furthermore,the modification of hemodynamic parameters in propranolol treated patients was not associated with changes in the angiotensin ratio.

Effect of Renin Angiotensin System Blockade on the Islet Microvessel Density of Diabetic Rats and Its Relationship with Islet Function

To investigate the effects of rennin angiotensin system blockade on the microvessel density in islets of diabetic rats and its relationship with islet function, diabetes model was created by feeding of high-caloric laboratory chow plus intraperitoneal injection of a small dose of streptozotocin （30 mg/kg）. After 8 weeks intervention with perindopril （AE, n=10） or valsartan （AR, n=10）, the islet function of the animals was evaluated by intravenous insulin release test （IVIRT）. The pancreases were immunohistochemically stained to analyze the content of insulin and vascular endothelial growth factor （VEGF） in the islets. The microvessel density （MVD） of islets was detected by counting CD34 positive cells. The hypoxia inducible factor （HIF）-1α mRNA expression in the islets was detected by RT-PCR. Compared with normal control group （NC, n=10）, the area under the curve for insulin from 0 to 30 min （AUCI0-30） of diabetes group （DM, n=8） was decreased by 66.3%; the insulin relative concentration （IRC） of βcell was decreased significantly; the relative content of VEGF was increased obviously [（–4.21±0.13） vs （–4.06±0.29）]; MVD in islets was decreased by 71.4%; the relative expression of HIF-1α mRNA was increased by 1.19 times （all P〈0.01）. Compared with DM group, the AUCI0-30 of AE and AR group was increased by 44.6% and 34.9% respectively; IRC was also increased significantly; the relative content of VEGF was decreased by 21.2% and 21.7% respectively; MVD was increased by 62.5% and 75.0% respectively; the relative expression of HIF-1α was decreased by 27.2% and 29.0% respectively （all P〈0.01 or P〈0.05）. There were no significant differences in the said indexes between group AE and AR. It is concluded that the blockade of RAS may ameliorate islets function of diabetic rats by increasing the MVD in islets.

Calcium channel blocker monotherapy versus combination with reninangiotensin system inhibitors on the development of new-onset diabetes mellitus in hypertensive Korean patients

Background In real practice, two or more antihypertensive drugs are needed to achieve target blood pressure. We investigated the comparative beneficial actions of combination therapy of renin-angiotensin system inhibitors (RASI), with calcium channel blockers (CCB) over CCB monotherapy on the development of new-onset diabetes mellitus (NODM) in Korean patients during four-year follow-up periods. Methods A total of 3208 consecutive hypertensive patients without a history of diabetes mellitus who had been prescribed CCB were retrospectively enrolled from January 2004 to December 2012. These patients were divided into the two groups according to the additional use of RASI (the RASI group, n = 1221 and the no RASI group, n = 1987). Primary endpoint was NODM, defined as a fasting blood glucose ≥ 126 mg/dL or hemoglobin A1c ≥ 6.5%. Secondary endpoint was major adverse cardiac events (MACE) defined as total death, myocardial infarction (MI) and percutaneous coronary intervention (PCI). Results After propensity score-matched (PSM) analysis, two propensity- matched groups (939 pairs, n = 1878, C-statistic = 0.743) were generated. The incidences of NODM (HR = 1.009, 95% CI: 0.700–1.452, P = 0.962), MACE (HR = 0.877, 95% CI: 0.544–1.413, P = 0.589), total death, MI, PCI were similar between the two groups after PSM during four years. Conclusions The use of RASI in addition to CCB showed comparable incidences of NODM and MACE compared to CCB monotherapy in non-diabetic hypertensive Korean patients during four-year follow-up period. However, large-scaled randomized controlled clinical trials will be required for a more definitive conclusion.

African Americans,hypertension and the renin angiotensin system

African Americans have exceptionally high rates of hypertension and hypertension related complications. It is commonly reported that the blood pressure lowering efficacy of renin angiotensin system(RAS) inhibitors is attenuated in African Americans due to a greater likelihood of having a low renin profile. Therefore these agents are often not recommended as initial therapy in African Americans with hypertension. However, the high prevalence of comorbid conditions, such as diabetes, cardiovascular and chronic kidney disease makes treatment with RAS inhibitors more compelling. Despite lower circulating renin levels and a less significant fall in blood pressure in response to RAS inhibitors in African Americans, numerous clinical trials support the efficacy of RAS inhibitors to improve clinical outcomes in this population, especially in those with hypertension and risk factors for cardiovascular and related diseases. Here, we discuss the rationale of RAS blockade as part of a comprehensive approach to attenuate the high rates of premature morbidity and mortality associated with hypertension among African Americans.

Nonalcoholic fatty liver disease and the renin-angiotensin system:Implications for treatment

Nonalcoholic fatty liver disease(NAFLD) is the commonest liver disease in Western countries.Treatment of NAFLD is currently based on lifestyle measures and no effective pharmacologic treatment is available so far.Emerging evidence,mainly from animal studies,suggests that the renin-angiotensin-aldosterone system may be of major importance in the pathogenesis of NAFLD and indicates that angiotensin-converting enzyme inhibitors(ACE-I) and angiotensin receptor blockers(ARBs) as a potentially useful therapeutic approach.However,data from human studies are limited and contradictory.In addition,there are few randomized controlled trials(RCTs) on the effects of ACE-I or ARB in patients with NAFLD and most data are from retrospective studies,pilot prospective studies and post hoc analyses of clinical trials.Accordingly,more and larger RCTs are needed to directly assess the effectiveness of ACE-I and ARBs in NAFLD.

Renin Angiotensin System Components and Cancer: Reports of Association

Renin-Angiotensin System (RAS) is involved with hypertension and other cardiovascular diseases. However, the association of RAS components to cancer still causes suspicion. To try to clarify this, here we aimed to show this association for three important components: Angiotensin Converting Enzyme 1 (ACE1), Angiotensin Type 1 Receptor (AGTR1) and Angiotensin Type 2 Receptor (AGTR2). The first articles show that association of RAS components with cancer dates back to the 70’s. ECA1 and AGTR1 have close association with cancer and ACE1 inhibitors or AGTR1 blockers are candidates to treatment of some tumors. Moreover, the action of AGTR2 is still controversial, but most studies show that the increased expression of AGTR2 can attack the cancer cells. In breast cancer, these components have also been widely studied and many works have shown that the correlation exists. Therefore specific target using these RAS components could be a beneficial, novel therapy to various tumors.

Prominent Roles of the Renin Angiotensin System in Atherosclerosis

The renin angiotensin system (RAS) is emerging as a prominent factor in the development of experimental atherosclerosis. We have previously demonstrated that the RAS is profoundly activated in hypercholesterolemia. This was demonstrated in LDLR-/-mice fed a saturated fat enriched diet and manifested as increased plasma concentrations of angiotensinogen and angiotensin peptides; especially angiotensin Ⅱ (AngⅡ).

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.

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.

Effects of highly potent atrial natriuretic peptide on circulating reninangiotensin-aldosterone system and cardiac function in dogs with ischemic heart failure

The effects of highly-potent atrial natriuretic peptide (HPANP) on circulating re nin-angiotensin-aldos-terone system (RAAS) and cardiac function were studied in an acute ischemic heart failure model. HPANP (6 μg/kg and 3 μg/kg) was infused intracoronarily. It was found that both doses of HPANP could cause significant decrease in plasma renin activity (PRA), angiotensin II (AII) and aldosterone (Ald). After the administraticn of HPANP, PRA, AII and Ald in the coronary sinus were decreased by 73. 2% (P<0.01), 68. o% (P<0.01) and 73. 6% (P<0.01), and the hormones in peripheral venous blood by 63. 3% (P<0.01), 53. 3% (P<0.01) and 64. 9% (P<0.01), respectively at the dose of 6 μg/kg. While PRA, AII and Ald in the coronary sinus and in peripheral venous blood decreased by 55. 9%, 55. 3%, 61. 9%, and 54. 0%, 42. 3%, 53, 3%, respectively at the 3μg/kg dose level. At the higher dose, HPANP increased left ventricular systolic pressure (LVSP, +13. 1%, P<0. 05), +dP/dtmax(+24.1 %, P<0.01), -dp/dtmax (+35.9%, P<0.01), and VCE(+28.9%, P<0.05). Mean arterial pressure and left ventricular end-diastolic pressure (LVEDP) were decreased (-15.0%, P<0.01, and 29. 6%, P<0.01, respectively). In contrast, the lower dose caused no significant changes of LVSP, +dp/dtmex,dp/dtmax and VCE(not including LVEDP, - 20. 5 %, P<0.05). Neither of the doses caused significant changes in heart rate and T value- Normal saline infusion has no effects on cardiac function and circulating RAAS- We conclude that in ischemic heart failure, intracoronary administration of HPANP can significantly suppress the activity of circulating RAAS, and improve cardiac function by reducing pre- and after-load of the heart, but has no direct myocardial effects.

肾素-血管紧张素系统在血管性痴呆大鼠心肌损伤中的作用

目的探讨肾素-血管紧张素系统在实验性血管性痴呆大鼠心肌损伤中的作用。方法24只成年雄性SD大鼠分为正常组、假手术组和模型组。Morris水迷宫用于评估大鼠学习记忆功能;免疫染色法观察心肌细胞横截面积和间质胶原蛋白分数以评估实验性血管性痴呆引起的心肌改变。检测血清中血管紧张素Ⅱ(AngⅡ)和血管紧张素1-7(Ang1-7)的浓度,以及心肌中血管紧张素转换酶(ACE)、血管紧张素转换酶2(ACE2)、AngⅡ、Ang1-7、血管紧张素1型(AT1)受体和Mas受体的蛋白表达水平。结果与假手术组和正常组比较,模型组大鼠存在明显的认知功能障碍(P<0.01)和心肌损伤(P<0.0001)。此外,模型组大鼠心肌中肾素-血管紧张素系统的ACE/AngⅡ/AT1轴上调(P<0.01),而ACE2/Ang1-7/Mas轴下调(P<0.05)。结论实验性血管性痴呆大鼠心肌损伤可能与肾素-血管紧张素系统失调有关。