Level Of Angiotensin II Research Articles

Serum Angiotensin II Level in Pediatric Patients with COVID-19 and its Correlation with the Disease Severity

Abstract Background Coronavirus disease 2019 (COVID-19) is a newly discovered RNA betacoronavirus infection. It has been caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin II (Ang-II) is a mitochondrial toxin that under normal circumstances is rapidly removed by angiotensin converting enzyme 2 (ACE-2). SARS-CoV-2 uses the receptor ACE-2 for host cell entry and viral replication. ACE-2 proteins are occupied and downregulated by SARS-CoV-2. ACE-2 downregulation has been directly linked to toxic over accumulation of Ang-II. Accumulating Ang-II triggers many severe and fatal conditions such as acute respiratory distress syndrome (ARDS). Aim of the Work To assess the serum level of Ang-II and correlate it with the severity of COVID-19 infection in pediatric patients. Patients and Methods This case control study was conducted on 45 positive COVID-19 RT-PCR children who were compared to age and sex matched 45 healthy controls. Clinical examination, laboratory assays and imaging studies were done for the patients group to assess the severity of COVID–19 infection. Serum Ang-II was measured by ELISA for both groups and correlated with clinical (heart rate, blood pressure, respiratory rate and oxygen saturation), laboratory (total leucocytic count, lymphocytes, neutrophils, serum ferritin, ESR and CRP) and radiological (chest x-ray and CORAD score of CT chest ) parameters of the patients. Results The median “IQR” of serum Ang-II was significantly higher in the COVID-19 patients than in the controls (100 (88-137) ng/L) versus 20 (15-25) ng/L) (p-value= 0.001). There were statistically significant positive correlations between serum Ang-II levels and different grades of clinical severity classification (rs = 0.92, p-value=0.001) and CORAD score of CT chest. On the other hand, no statistically significant correlations were found between serum levels of Ang-II and total leucocytic count, lymphocytes, neutrophils, ESR and CRP. Conclusion Serum Ang-II could be used as a biomarker in predicting the severity of COVID-19 infection in pediatrics.

Abstract 12379: AT1-AA (Angiotensin II Type 1 Receptor Autoantibody) Aggravates Abdominal Aortic Aneurysm Through Activating AT1R/Gq Allosterically

Background: Angiotensin II type 1 receptor (AT1R) is a key mediator of the rennin-angiotensin-aldosterone system (RAAS). Autoantibodies against AT1R (AT1-AA), as an activator of AT1R, was found in abdominal aortic aneurysm (AAA) related diseases, such as hypertension and atherosclerosis. However, the role of AT1-AA in AAA is still unclear. Methods: We used angiotensin II (AngII)-infused male ApoE -/- mice model of AAA. Ultrasonography measurement, histological assessment, western blot, qRT-PCR and RNA sequencing were used to assess the severity of AAA. Nanoluciferase-based bioluminescence resonance energy transfer (NanoBRET) assay, radio assay of receptors and homogeneous time resolved fluorescence (HTRF) were used to measure the activation feature of AT1R and the affinity of AT1R with AT1-AA or AngII. Results: AT1-AA increased the incidence of AAA (vehicle vs. AT1-AA: 47% vs. 81%; P<0.05), which can be attenuated by AT1R blocker Candesartan. Furthermore, AT1-AA greatly increased severity of AAA, due to augmenting the diameter of abdominal aorta and the degradation of elastin by enhancing the expression of MMP2/9 (matrix metalloproteinase) and the accumulation of inflammatory cells. And AT1-AA could induce phenotypic switch of smooth muscle cells. But AT1-AA does not increase the plasma level of AngII. Mechanically, AT1-AA enhanced AngII-induced recruitment of Gq, but not β-arrestin1/2. AT1-AA potentiated the AngII-mediated Gq-dependent inositol phosphate (EC50 shift=3.829 nM) and the activation of PKC and ERK1/2. The responses were abolished by AT1R blocker and Gq inhibitor. The affinity of AT1-AA for the AT1R in cells was calculated to be 75.49 ± 4.7 nM. AT1-AA cannot compete for the binding of AngII to AT1R. However, AT1-AA significantly potentiated the binding of AngII with AT1R allosterically (mean K D ± SEM: 34.11 ± 0.9765 nM at 0 nM AT1-AA vs. 25.63 ± 1.826 nM at 100 nM AT1-AA; p<0.05), without altering the maximum binding. Conclusion: AT1-AA, as an allosteric activator of AT1R, promotes AAA through increasing the affinity of AngII with AT1R and activating Gq biasedly.

Enalaprilat as a new means of preventing the development of retinopathy of prematurity.

In a rat model of experimental retinopathy of prematurity (ROP), the safety of enalaprilat and its effect on the level of angiotensin-converting enzyme (ACE) and angiotensin-II (AT-II) in the vitreous body and retina were investigated. The study was performed on 136 newborn Wistar rat pups divided into 2 groups: group A - experimental (animals with ROP, n=64) and group B - control (n=72). Each group was further divided into 2 subgroups: A0 and B0 (n=32 and n=36, respectively) - animals that did not receive injections of enalaprilat, and A1 and B1 (n=32 and n=36, respectively) - animals treated with daily intraperitoneal (i.p.) injections of enalaprilat (0.6 mg/kg of body weight). This treatment started on day 2 and lasted either to day 7 or to day 14 in accordance with the therapeutic scheme. Animals were taken out of the experiment on day 7 and day 14. In samples of the vitreous body and retina, the content of ACE and AT-II was determined by enzyme immunoassay. On day 7 in subgroups A1 and B1 the levels of ACE and AT-II in the vitreous did not differ, while on day 14 were lower than in subgroups A0 and B0, respectively. Changes in the parameters studied in the retina were somewhat different from those found in the vitreous body. On the seventh day, the level of ACE in the retina of animals of subgroup B1 did not differ significantly from subgroup B0, and in subgroup A1 it was increased compared to subgroup A0. On day 14, its significant decrease was noted in subgroups A1 and B1 as compared with subgroups A0 and B0. At the same time, the level of AT-II in the retina of rat pups of subgroup B1 was lower than in subgroup B0, both on day 7 and day 14. On day 7, the concentration of AT-II, as well as the concentration of ACE, increased in subgroup A1 as compared to subgroup A0. On day 14, this parameter in subgroup A1 was significantly lower as compared to subgroup A0, but significantly higher than in subgroup B1. It should be noted that i.p. injections of enalaprilat, increased a death rate of animals of both groups. The use of enalaprilat, starting from the preclinical period of the ROP development, led to a decrease in the activity of the renin-angiotensin system (RAS) in ROP animals at the onset of retinopathy in the experimental model used. This opens up prospects for considering enalaprilat as a means of preventing the development of this pathology; however, the recognized high toxicity of the drug requires further studies and correction of the timing of its administration and dosage in order to achieve a balance of efficacy and safety of use in order to prevent the development of ROP in children.

FEATURES OF THE COURSE OF ARTERIAL HYPERTENSION IN PATIENTS AFTER COVID-19

Introduction. Arterial hypertension (AH) is one of the most common comorbidities in patients with COVID-19. A number of studies have revealed a more severe course of COVID-19 (coronavirus disease (CVD) in patients with hypertension. The problem of studying the association between AH and COVID-19 is also very relevant from an etiopathogenetic point of view, since, both in the development of COVID-19 and in the pathogenesis of AH, one of the key places is occupied by the components of the renin-angiotensin-aldosterone system (RAAS) and, first of all, turn, angiotensin-converting enzyme-2 (ACE-2) and angiotensin II (AII). It has been established that the penetration of the SARS-CoV-2 virus into the body occurs by binding to the RAAS enzyme - ACE-2. This leads to a decrease in the level of ACE-2 and to an increase in the level of AII, which initiates a cytokine storm, damage to the lungs and contributes to the development of severe CVD. On the other hand, AII is one of the most powerful vasoconstrictor factors and plays an extremely important role in the mechanisms of development and progression of hypertension. However, despite the already long period of the COVID-19 pandemic, the features of the course of hypertension in patients who have had this disease have not been adequately studied. The problem of clinical and pathogenetic relationships between AH and COVID-19 remains relevant in 2022, after the start of a new wave of COVID-19 with the dominant Omicron strain. Aim: study of the features of the course of hypertension in patients after COVID-19. Materials and methods. 82 patients with AH were examined before and 6-12 weeks after COVID-19 disease. Among the examined patients, 68 patients (83%) had moderate COVID-19, 14 patients (17%) had severe COVID-19. All patients before and after infection with COVID-19 underwent a general clinical laboratory and instrumental examination. Results. A significant negative impact of COVID-19 on the nature of the course of hypertension was revealed: an increase in the severity of hypertension, the frequency of cardiac arrhythmias, the frequency and severity of heart failure, a decrease in kidney function, destabilization of existing type 2 diabetes and development of new cases of diseases, progression of lipid metabolism disorders and coronary heart disease. A significant contribution to the worsening of the course of AH after CVD is made by the formation of «ongoing symptomatic COVID-19» and astheno-depressive syndrome. Taking into account current data, COVID-19 can directly lead to a worsening of hypertension due to a decrease in ACE-2 levels and an increase in the production of AII, which plays a key role in the pathogenesis of hypertension. Conclusions. Postponed COVID-19 significantly worsens the course of hypertension, which increases the overall risk of complications and indicates the need for timely initiation of adequate comprehensive treatment. Key words: coronavirus disease -19- COVID-19, arterial hypertension, renin- angiotensin- aldosterone system, angiotensin converting enzyme-2, angiotensin ІІ.

Angiotensin(1-7) Improves Islet Function in Diabetes Through Reducing JNK/Caspase-3 Signaling.

The aim of this study is to investigate whether Angiotensin (1-7), the physiological antagonist of Angiotensin II (AngII), has antidiabetic activity and the possible mechanism. Male Wistar rats were randomly divided into 3 groups: control group fed the normal diet, DM group fed high-fat diet and injected with STZ, and Angiotensin (1-7) group receiving injection of STZ followed by Angiotensin (1-7) treatment. Serum Ang II, fasting blood glucose, insulin, HOMA-IR, and HOMA-beta were determined in control, diabetes and Angiotensin (1-7) groups. The increased AngII and insulin resistance in diabetes group were accompanied by changes in islet histopathology. However, Angiotensin (1-7) improved the islet function and histopathology in diabetes without affecting the level of AngII. Western blot confirmed that Angiotensin (1-7) decreased the cleaved caspase 3 levels in pancreas of DM. The increased expression of JNK, Bax, and Bcl2 genes under diabetic conditions were partially reversed after Angiotensin (1-7) administration in pancreas. Immunofluorescence analysis showed that p-JNK was markedly increased in islet of DM rats, which was markedly alleviated after Angiotensin (1-7) treatment. Furthermore, Angiotensin (1-7) reversed high glucose(HG) induced mitochondrial apoptosis augments. Finally, Angiotensin (1-7) attenuated the apoptosis of INS-1 cells through reducing JNK activation in diabetes, which was blocked by anisomycin (a potent agonist of JNK). Our findings provide supporting evidence that Angiotensin (1-7) improved the islet beta-cells apoptosis by JNK-mediated mitochondrial dysfunction, which might be a novel target for the treatment and prevention of beta-cells dysfunction in DM.

Evaluation of Renal and Cardioprotective Potential of the Biofield Energy Treated Proprietary Test Formulation on L-NAME and High Fat Diet-Induced Cardiovascular Disorders in Sprague Dawley Rats

The aim of this study was to evaluate the impact of Biofield Energy Treated/Blessed Proprietary Test Formulation and Biofield Energy Treatment/Blessing per se on kidney biomarkers on L-NAME and high fat diet (HFD)-induced cardiovascular disorders in Sprague Dawley rats. In this experiment, the functional kidney biomarkers such as epinephrine/adrenaline, inducible nitric oxide synthase (iNOS), angiotensin-II, C-reactive protein (CRP), and renin were measured using ELISA assay. A test formulation was formulated including minerals (magnesium, zinc, copper, calcium, selenium, and iron), vitamins (vitamin C, vitamin B6, vitamin B12, vitamin B9, and vitamin D3), cannabidiol (CBD) isolate, Panax ginseng extract, and β-carotene. The components of the test item were divided into two; one section was defined as the untreated test formulation, while the other part and three group of animals received Mr. Mahendra Kumar Trivedi’s Biofield Energy healing/Blessing remotely for about 3 minutes. The results showed that the level of adrenaline was reduced by 31.62%, 19.58%, 34.32%, 37.07%, and 29.87% in the G5 (L-NAME + HFD + the Biofield Energy Treated test formulation), G6 (L-NAME + HFD + Biofield Energy Treatment per se to animals from day -15), G7 (L-NAME + HFD + the Biofield Energy Treated test formulation from day-15), and G8 (L-NAME + HFD + Biofield Energy Treatment per se plus the Biofield Energy Treated test formulation from day-15), and G9 (L-NAME + HFD + Biofield Energy Treatment per se animals plus the untreated test formulation) groups, respectively as compared to the disease control group (G2). Moreover, the level of iNOS was reduced by 56.76%, 49.51%, 61.79%, 57.63%, and 62.44% in the G5, G6, G7, G8, and G9 groups, respectively, as compared to the disease control group (G2). Additionally, the level of angiotensin-II was decreased by 41.09%, 34.92%, 60.65%, 53.28%, and 60.09% in the G5, G6, G7, G8, and G9 groups, respectively, as compared to the G2 group. The level of CRP was decreased by 47.21%, 38.89%, 59.81%, 55.52%, and 64.02% in the G5, G6, G7, G8, and G9 groups, respectively as compared to the G2 group. Besides, the level of renin was decreased by 20.27%, 20.13%, 12.99%, and 25.73% in the G5, G7, G8, and G9 groups, respectively as compared to the G2 group. Overall, the data suggested significance improvement of vital functional kidney biomarkers of the Biofield Energy Treated/Blessed test formulation and Biofield Energy Treatment per se along with preventive measure on the animal with respect to various pathological conditions that might be beneficial various types of cardiovascular disorders. Therefore, the results showed the significant slowdown the inflammation-related cardiovascular disease progression and its complications/symptoms in the preventive Biofield Energy Treatment group per se and/or Biofield Energy Treated/Blessed Test formulation groups (viz. G6, G7, G8, and G9).

Evaluation of Cardiac Biomarkers after Administration of the Biofield Energy Treated Proprietary Test Formulation on L-NAME and High Fat Diet-Induced Cardiovascular Disorders in Sprague Dawley Rats

Recent medical advances, cardiovascular disorders (CVDs) continue to be major health concerns, and related high mortality. In this context, investigation of the functional biomarkers involved in the development of CVDs to be an active field of study. The study was aimed to evaluate the effect of Biofield Energy Treated/Blessed Proprietary Test Formulation and Biofield Energy Treatment per se on heart biomarkers in L-NAME and high fat diet (HFD)-induced cardiovascular disorders in Sprague Dawley rats. The functional heart biomarkers such as epinephrine, inducible nitric oxide synthase (iNOS), angiotensin-II, C-reactive protein (CRP), cholesterol, troponin-1, and Na+ /K+ -ATPase were measured using standard ELISA assay. A test formulation was formulated including minerals (magnesium, zinc, copper, calcium, selenium, and iron), vitamins (ascorbic acid, pyridoxine HCl, vitamin B9 , cyanocobalamin, and cholecalciferol), Panax ginseng extract, β-carotene, and cannabidiol isolate. In this experiment, nine groups were allocated, in which four were preventive maintenance groups. Each ingredients of the test formulation were divided into two parts; one section was defined as the untreated test formulation, however other part of the test formulation received Biofield Energy Healing/Blessing remotely for about 3 minutes by Mr. Mahendra Kumar Trivedi. Among nine groups, three groups of animals were also received Biofield Energy Healing Treatment per se (at day-15). The results showed that the level of epinephrine was significantly (p≤0.001) reduced by 72.49%, 63.83%, 80.21%, 89.53%, and 84.97% in the G5 (L-NAME + HFD + the Biofield Energy Treated test formulation), G6 (L-NAME + HFD + Biofield Energy Treatment per se to animals from day -15), and G7 (L-NAME + HFD + the Biofield Energy Treated test formulation from day -15), G8 (L-NAME + HFD + Biofield Energy Treatment per se plus the Biofield Energy Treated test formulation from day -15), and G9 (L-NAME + HFD along with Biofield Energy Treatment per se animals plus the untreated test formulation) groups, respectively as compared to the disease control group (G2). The results showed that the level of iNOS was reduced by 15.19%, 15%, and 23.94% in the G5, G8, and G9 groups, respectively as compared to the untreated test formulation group (G4). Moreover, the level of angiotensin-II was decreased by 29.57%, 18.62%, 34.16%, and 33.35% in the G5, G7, G8 and G9 groups, respectively, as compared to the G2 group. The level of CRP was decreased significantly by 17.57%, 44.94% (p≤0.001), and 41.36% (p≤0.001) in the G5, G8, and G9 groups, respectively as compared to the G2 group. Besides, the level of cholesterol was significantly (p≤0.001) decreased by 27.60%, 23.68%, 28.71%, 41.26%, and 36.94% in the G5, G6, G7, G8, and G9 groups, respectively as compared to the G2 group. The level of troponin-1 was decreased significantly (p≤0.05) by 27.53% in the G9 group as compared to the G2 group. The level of Na+ /K+ -ATPase was significantly increased by 42.16%, 87.87% (p≤0.05), 65.95% (p≤0.05), 31.40%, and 18.48% in the G5, G6, G7, G8, and G9 groups, respectively than G2 group. Overall, the data suggested significance improvement of vital functional heart biomarkers of the Biofield Energy Treated/Blessed test formulation and Biofield Energy Treatment per se along with preventive measure on the animal with respect to various pathological conditions that might be beneficial various types of cardiovascular disorders. Thus, the results showed the significant reduction of cardiovascular disease progression and its complications in the preventive treatment groups (viz. G6, G7, G8, and G9).

Angiotensin-II as a Trigger Factor in the Development of Retinopathy of Prematurity

The multifactorial nature of the retinopathy of prematurity (ROP) pathogenesis, makes the thorough study of the mechanism of pathological retinal neovascularization actual. However recently the attention of scientists has been attracted by the participation of renin-angiotensin system (RAS) in the development of retinal vasoproliferative diseases. Purpose: to study the role of AT-II in the pathogenesis of experimental ROP (EROP) in the original model of the disease. Material and methods. To reproduce EROP Wistar rats (n = 15) were exposed to the oxygen concentration varying from 60 to 15% every 12 hours for 14 days from the first day after birth followed by room air for 7 days. Throughout the experiment, the room maintained a constant temperature (+26 °C) and light regime (12 hours a day, 12 hours a night) modes. Control rats (n = 12) were born and kept under normal oxygen content (21 %). Batches of EROP (n = 5) and control (n = 4) rats were sacrificed on 7, 14 and 21 days. All rats underwent binocular enucleation, after which every eyeball was opened on the limb, the cornea and lens were removed with the remains of a persistent vascular bag and a hyaloid artery. Retinas were isolated, homogenized and stored at -20 °C. Angiotensin-II (AT-II) in homogenates was measured using the IFA kit. Results. On the 7th day of the experiment, the level of AT-II in the retina of the experimental group rats was 0.19 ± 0.02 pg/mg protein that was significantly higher than in controls (0.12 ± 0.01 pg/mg protein). On the 14th and 21st days concentrations of AT-II in EROP and control groups had no significant difference. Conclusion. On the 7th day of the experiment, i.e. at the period corresponding to the existence of avascular retinal zones in both groups concentration of AT-II in the retinas of rats with EROP was significantly higher than in controls. This fact indicate the role of this proangiogenic factor in the induction of pathological neovascularization in ROP. Possible prognostic function of this parameter during the period before ROP manifestation has undoubted practical significance.

Influence of inhibitors of the renin-angiotensin system on risk of acute respiratory distress syndrome in Danish hospitalized COVID-19 patients.

COVID-19, the disease associated with SARS-CoV-2 infection, is in some 20% of acutely affected patients associated with respiratory distress syndrome (ARDS) often necessitating respirator treatment and associated with a high mortality [1–3]. Epidemics in Wuhan in China and Lombardy in Italy have been devastating, and SARS-CoV-2 has developed into a pandemic necessitating urgent worldwide co-operation. Until effective treatment of COVID-19 including a useful vaccination against SARS-CoV-2 is found, it is important to seek ways of limiting or avoiding ARDS. Virus-related ARDS is initiated from a high level of angiotensin II (Ang-II) via the type 1 receptor pathway [4], and Ang-II has already been demonstrated to be high in COVID-19 and linearly associated with lung injury [5]. Inhibitors of the renin–angiotensin system (RASi), cornerstones of treatment of patients with hypertension and heart failure, have attracted attention as they may in theory influence the Ang-II level in COVID-19 and thereby the risk of ARDS [4,6]. In short, Ang-II activity is influenced by the balance of Ang-converting enzyme (ACE) and ACE2 receptor activity. The activity of ACE2 normally lowers the level of Ang-II, but SARS-CoV-2 virus binds to ACE2 receptors, lower their activity and hence increase Ang-II activity [1]. While RASi lower Ang-II levels, and may in this respect be helpful, chronic RASi treatment may on the other hand also increase pulmonary ACE2-receptor numbers hence providing a possible higher SARS-CoV-2 viral load. As suggested from animal experiments, chronic treatment with RASi can therefore, in theory, both increase and lower the risk of ARDS in SARS-CoV-2-infected patients. Studies early listed heart disease, hypertension, and diabetes as risk factors for ARDS [1–3], but unfortunately medication has not yet been reported on, and clinical data on the relative importance of RASi for outcome in COVID-19 are now urgently needed. Approved by the Danish Patient Safety Authority and the Danish Data Protection Agency, we related medication to outcome in all SARS-CoV-2 PCR positive patients, who, between 1 March and 1 April 2020, had remained admitted with infection to hospital for at least 24 h in two of five Danish regions (2.6 million inhabitants). We looked at a composite outcome of ICU-admission or death and determined the relative risk of RASi in logistic regression models estimating odds ratios of ICU-admission adjusted for time to event or censoring. Out of a total of 2700 PCR positive patients, 689 patients (25.5%) were acutely ill and remained hospitalized for at least 24 h. Of these 689 patients 71.1% were 60 years or older; 58.1% were male; and 32.7% were treated with RASi. Out of 689 patients 525 did not experience an outcome, whereas 164 (23.8%) experienced ICU and/or death (Table 1). Eighty-four percent of the patients admitted to ICU needed respirator treatment. Mean risk time from having been admitted for 1 day till ICU was only 2.04 further days (SD 2.29; range 0–10). Medical treatment for chronic obstructive pulmonary disease, statins, antithrombotic drugs, and RASi were equally prevalent among outcome groups, while beta-blockers and spironolactone seem unevenly distributed with higher prevalence among patients, who were admitted to the ICU or died (Table 1). Glucose-lowering drugs tended to be unevenly distributed between groups (P = 0.087). In logistic regression analyses incorporating sex, age, risk-time, and selected medical treatment, we found that male sex, increasing age, and the use of beta-blockers independently increased odds for ICU-admission or death, but RASi treatment did not.TABLE 1: Characteristics of patients hospitalized for at least 24 h with PCR proven COVID-19, stratified by a composite outcome of admission to ICU or deathCurrent consensus [4,6] recommends not changing RASi treatment in patients with SARS-CoV-2 infection. Whereas we found other heart failure medication to be of importance, probably mainly reflecting the underlying cardiac phenotype and comorbidity, our data do not suggest any significant influence from chronic RASi treatment and hence our data bring some reassurance to the consensus of not changing RASi medication. Randomized studies on RASi treatment intervention in patients at risk of COVID-19 should consider timing the intervention early in the course of the disease or well before infection, since if patients do develop ARDS they do so after a very short time period. ACKNOWLEDGEMENTS Conflicts of interest There are no conflicts of interest.

Urinary excretion of components of the renin-angiotensin-aldosterone system in patients having localized renal cancer.

e14725 Background: The aim of the study was exploring the content of components of the renin-angiotensin-aldosterone system (RAAS) in the urine of renal cancer (RC) patients depending on the clinical and morphological characteristics. Methods: In the urine of patients having localized renal cancer Т1N0M0 (the main group, n = 40) the level of angiotensinII (ATII), angiotensin-converting enzymes (ACE and ACE2) was studied by the ELISA with excretable creatinine taken into account in order to eliminate the differences of diuresis. The control group was made up of 35 healthy donors. Results: In patients of the main group, the content of ATP in the urine is 71,5% higher (р = 0,003) than in the healthy donors. In 50% of the patients, the range of fluctuations of ATI in the urine from the lower to the upper quartile amounts to 4,2-9,8 pg/µmol of creatinine against 2,1-5,2 pg/µmol of creatinine in the healthy ones.The level of ACE and ACE2 in the patients as compared to the healthy donors is also 35,4% and 24,5% higher, respectively (at p < 0,05). The proportion of increment ΔATII/ΔACE in the patients amounted to 2,2±0,1as compared to the healthy donors, that of ΔATII/ΔACE2 – to3,2±0,2. Meanwhile, ΔACE/ΔACE2 was 1,6±0,1, which confirms the predominance of the activity of ACE. In patients of the main group, no statistically valid difference of the urinary excretion value of ATII, ACE and ACE2 has been identified between the subgroups depending on the RC stage T1a, Т1bas well as on dimensions of the tumor nodes. However, in case of the RC with G2 tumor differentiation grade as compared to the G1, the content of ATII, ACE and ACE2 in the urine is 3,5; 2,5 and 2,1 times higher, respectively (p < 0,05). Conclusions: In patients having localized renal cancer, increased urinary excretion of components of the renin-angiotensin-aldosterone system has been found. The content of angiotensin II in the urine exceeds the activity of angiotensin-converting enzymes, which may be related to the alternative ways of its formation under tumor growth. The content of the RAAS components in the urine in patients having localized renal cancer does not depend on the stage and dimensions of the tumor but it correlates with the differentiation grade.

COPD rat model is more susceptible to cold stress and PM2.5 exposure and the underlying mechanism

The purpose of this study is to verify the hypothesis that chronic obstructive pulmonary disease (COPD) model rat is more susceptible to cold stress and fine particulate matter (PM2.5) exposure than the healthy rat, and explore the related mechanism. COPD rat model, established with cigarette smoke and lipopolysaccharide intratracheal instillation, were exposed to cold stress (0 °C) and PM2.5 (0, 3.2, 12.8 mg/ml). After that, the levels of superoxide dismutase, inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein 1 (MCP-1) and angiotensin Ⅱ (Ang-Ⅱ) in lung were measured, as well as the expression levels of lung 8-hydroxy-2-deoxyguanosine (8-OHdG), nuclear factor kappa B (NF-κB), heme-oxygenase-1 (HO-1) and nuclear factor erythroid-2-related factor 2 (Nrf2). There were significant positive relationships between PM2.5 and lung level of iNOS, TNF-α, MCP-1 and Ang-Ⅱ, lung function and pathologic damage in COPD rats. The HO-1, NF-κB and 8-OHdG were found highly expressed in COPD rat lung, particularly at the higher PM2.5 dose of cold stress groups, while Nrf2 was found declined. Thus, COPD rats may be more susceptible to cold stress and PM2.5 exposure. Cold stress may aggravate PM2.5-induced toxic effects in the lung of COPD rats through increasing Ang-Ⅱ/NF-κB signaling pathway and suppressing Nrf2 signaling pathway.

An angiotensin-converting enzyme inhibitor in the combination treatment of rheumatoid arthritis

Angiotensin-converting enzyme (ACE) inhibitors have anti-inflammatory and antiproliferative properties and can affect the processes of angiogenesis, by reducing the effects of angiotensin II (ATII). The use of ACE inhibitors in the combination therapy of rheumatoid arthritis (RA) can be also effective for monitoring disease activity and for reducing a cardiovascular risk. Objective: to evaluate the efficacy of an ACE inhibitor in the combination therapy of RA. Patients and methods. Eighty-four patients with RA and endothelial dysfunction were examined; the mean age was 40.12±10.2 years; the mean disease duration was 4.22±3.43 years. All the patients had a blood level of ATII of >9 pg/ml. Enzyme immunoassay was used to measure the levels of tumor necrosis factor-α (TNF-α) (Vector-Best, Russia), intercellular adhesion molecules 1 (ICAM-1) (Diaclone, France), vascular endothelial growth factor (VEGF) and ATII (Diagnostic, Canada). Wrist ultrasonography using the Doppler ultrasound apparatus ESAOTE MyLAB40 was carried out to assess synovial vascularization. The patients were divided into two groups. Group 1 included 43 patients who were assigned to receive standard therapy for RA according to the rheumatic disease treatment protocols; Group 2 comprised 41 patients who received the standard therapy plus ACE inhibitors 2.5–5 mg/day. Results. The use of ACE inhibitors in the 12-month combination therapy of RA patients led to an improvement in the endothelial regulation of vascular tone, to a decrease in the blood concentration of ICAM-1, to a reduction in the intensity of synovial angiogenesis and in the blood level of VEGF by 39%, and a more significant drop in the levels of CRP and TNF-? and in DAS28 by 1.2 scores as compared to those in the standard therapy.

The Variations in Blood Pressure Values in Deadsea and Sea Level in Jordan are not Influenced by the Level of Angiotensin Ii

Introduction: hypertension may be affected by environment. The variation of altitudes has been reported to play a role in hypertension. In Jordan, we have an environment rich in diversity as having areas in the sea level and others in the lowest depth in the world (the Dead Sea). Objectives: to examine the impact of altitudes on the level of angioten II among study participants. Methods and subjects: across sectional design was conducted. Two areas were included: the Dead Sea and the Sea level area, Jordan. The study sample included a total of 1000 participants of them 500 participants were included from each area. All participants were males, matched for age grouping, and they were apparently healthy. A working paper was made for each participant which included study variables such as blood pressure, weight, height, waist circumference, heart rate per minute, the level of angiotensin II, and packed cell volume (PCV). We analyzed data using SPSS version 20. All data were included and represented as mean and standard deviation. The relations between variables were computed using independent T test. Significance was considered at alpha <0.05. Study findings: there were no statistical differences between study groups for all variables except systolic blood pressure which its mean was 122.42±10.53 mmHg in the area of Dead Sea and this was significantly higher than that of the Sea level (118.07±11.64) (p=0.001). The mean of blood pressure in the Dead Sea was 91.64 ± 8.90 mmHg, and this was significantly higher than that of the Sea level (89.84 ± 8.72) (p=0.001). The level of angiotensin II was 8.48±4.65pg/ml in the Dead Sea area, and this was less than that of the Sea level (11.21± 6.05pg/ml). The difference in means for angiotensin II was not statistically significant. Conclusion: the altitude differences in the study area affected, but not significantly, the level of angiotensin II and significantly the level of systolic blood pressure.

The Higher Response of Vascular Endothelial Growth Factor and Angiotensin-II to Human Chorionic Gonadotropin in Women with Polycystic Ovary Syndrome.

This research investigated the response of vascular active factors, vascular endothelial growth factor (VEGF) and angiotensin-II (AT-II) to ovarian stimulation during 24 hours in patients with polycystic ovary syndrome (PCOS). In this clinical trial study, 52 patients with PCOS and 8 control cases were stimulated with human chorionic gonadotropin (HCG) on the 4(th) to 7(th) day of the patients' natural or induced menstrual cycles. We measured VEGF and AT-II by radioimmunoassay before the injection (0 hour) and 3, 8, 12, 18 and 24 hours after the stimulation. After ovarian stimulation, there was substantially higher level of VEGF in typical PCOS patients than the other three groups at the 3 hour time point (p<0.05), while there were no significant differences in VEGF at all the other time points among the four groups. As for AT-II, before and at all time points after the ovarian stimulation, it seemed that the AT-II levels in patients' sera with different phenotypes of PCOS by the Rotterdam criteria were all higher than in the control group although the differences were not statistically significant. The level of AT-II in typical PCOS patients was also significantly higher than the other three groups at the 3 hour time point (p<0.05), while no significant differences at all the other time points among the four groups were observed. The response to the stimulation varied among patients with different phenotypes of PCOS according to the Rotterdam criteria. Serum VEGF and AT-II were possible contributors to an increased risk of developing ovarian hyperstimulation syndrome (OHSS) in patients with typical PCOS during the early follicular phase (3 hours) after ovarian stimulation ( NCT02265861).

ACE DD genotype associated with the female Chronic Kidney Disease patients of Tamilnadu population

BackgroundThe Renin-Angiotensin System (RAS) is an important regulator for blood pressure and kidney disease. The level of vaso active peptide Angiotensin-II is mainly determined by the RAS enzyme angiotensin converting enzyme-1 (ACE-1). AimTo investigate the association of ACE I/D polymorphism and Chronic Kidney Disease (CKD) in south India. MethodsIn the present study, we have collected CKD patients (n=147) and control subjects (n=211) from Tamilnadu. Genotyping was carried out by polymerase chain reaction (PCR) on the basis of allele specific primers. ResultsThe DD genotype is associated with the female population (OR-CI=2.40 (1.05–5.51), p=0.04) as compared to the male population (OR-CI=0.75 (0.37–1.51), p=0.42). Further, we found the over representation of “I” – allele (homozygous II and heterozygous ID) in unaffected males [OR (CI) – 0.58 (0.32–1.04), p=0.07] which suggests its protective role in male population. ConclusionThe DD genotype of ACE is associated with CKD in south India.

Aqueous extract of dioscorea opposita thunb. normalizes the hypertension in 2K1C hypertensive rats

BackgroundDioscorea opposita Thunb. (Huai Shan Yao, DOT), a common staple food in China, has been used for more than 2000 years in traditional Chinese medicine (TCM) to treat different systemic diseases including hypertension. The objective of this study was to investigate the possible antihypertensive effects of the aqueous extract of (DOT) in renovascular hypertensive rats as well as the mechanism in reducing blood pressure.MethodsThe two-kidney one-clip (2K1C) Goldblatt model of renovascular hypertension was used in Wistar rats. Rats with captopril, low-dose DOT and high-dose DOT treated 2K1C groups for 6 weeks. The blood pressure, cardiac mass index (heart weight/body weight), plasma level of angiotensin-II (Ang-II), endothelin-1(ET-1), superoxide dismutase (SOD) and malondialdehyde (MDA) were evaluated.ResultsDOT significantly reduced mean systolic and diastolic blood pressure after treatment. DOT also significantly increased plasma SOD activity but decreased plasma MDA concentration. Renal function was improved with captopril and DOT. DOT reduced plasma Ang-II activity and plasma ET concentration. They couldalso significantly reduce the left ventricular hypertrophy and cardiac mass index.ConclusionsOur results suggest that DOT may have an antihypertensive effect on hypertension by inhibit ET-converting enzyme and antioxidant activity, which warrant further exploration.

Angiotensin-II promotes Na+ uptake in larval zebrafish, Danio rerio, in acidic and ion-poor water

The contribution of the renin-angiotensin system (RAS) to Na(+) uptake was investigated in larval zebrafish (Danio rerio). At 4 days post fertilization (dpf), the level of whole-body angiotensin-II (ANG-II) was significantly increased after 1- or 3-h exposure to acidic (pH=4.0) or ion-poor water (20-fold dilution of Ottawa tapwater), suggesting rapid activation of the RAS. Long-term (24 h) treatment of 3 dpf larvae with ANG-I or ANG-II significantly increased Na(+) uptake which was accompanied by an increase in mRNA expression of the Na(+)-Cl(-) cotransporter (zslc12a10.2). Induction of Na(+) uptake by exposure to ANG-I was blocked by simultaneously treating larvae with lisinopril (an angiotensin-converting enzyme inhibitor). Acute (2 h) exposure to acidic water or ion-poor water led to significant increase in Na(+) uptake which was partially blocked by the ANG-II receptor antagonist, telmisartan. Consistent with these data, translational knockdown of renin prevented the stimulation of Na(+) uptake following exposure to acidic or ion-poor water. The lack of any effects of pharmacological inhibition (using RU486), or knockdown of glucocorticoid receptors on the stimulation of Na(+) uptake during acute exposure to acidic or ion-poor environments, indicates that the acute effects of RAS occur independently of cortisol signaling. The results of this study demonstrate that the RAS is involved in Na(+) homeostasis in larval zebrafish.

Clinical Implications

HomeHypertensionVol. 62, No. 1Clinical Implications Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBClinical Implications Originally published1 Jul 2013https://doi.org/10.1161/HYP.0b013e31829d4408Hypertension. 2013;62:2Angiotensinogen Expression in Human Adipose Tissue (page 41)Blood pressure is a heritable trait; the genetic causes of essential hypertension remain unclear. Despite being the first gene linked to hypertension, the importance of polymorphisms in angiotensinogen, the precursor to angiotensin-II, remains controversial. The renin–angiotensin system has both endocrine and intracrine functions controlling arterial pressure. The mechanisms regulating angiotensinogen expression is complicated. Because sequence variants in the promoter may differentially affect transcription factor binding, the mechanisms regulating angiotensinogen may differ depending on the polymorphism(s) carried. The current issue of Hypertension reports an effective strategy to examine whether variation in the angiotensinogen promoter effects its expression through differential binding of transcription factors in adipose tissue. The investigators report increased expression of angiotensinogen mRNA and binding of the transcription factor USF2 in chromatin specifically from the −20C allele in subcutaneous adipose tissue from subjects heterozygous for the −20A/C alleles of angiotensinogen. Thus, subjects carrying high-expressing alleles may have increased levels of angiotensinogen and angiotensin-II in some fat depots. This may be clinically important because circulating angiotensinogen derived from adipose tissue is increased in obesity and evidence implicates a role for angiotensin-II derived from adipose angiotensinogen in the regulation of metabolism and blood pressure. Consequently, further studies will need to assess whether this and other polymorphisms control the level of angiotensin-II in hypertensive and obese subjects.Download figureDownload PowerPointCD8+ T Cells and Chemokines in Human Hypertension (page 126)The pathogenic role of T cells in the development of hypertension has been well documented in animal studies. However, the existence of T-cell–driven inflammation in human hypertension has not been demonstrated. In this issue of Hypertension, Youn et al reported an increased fraction of immunosenescent, proinflammatory, cytotoxic CD8+ T cell, and increased circulating levels of T cell chemokines (MIG, IP-10, and I-TAC) in patients with hypertension. In patients with hypertensive nephrosclerosis, I-TAC was expressed more abundantly in the proximal and distal tubules. This evidence, along with an increased level of serum granzyme B, supports the increased activity of cytotoxic T cells in human hypertension. The authors provide evidence for the first time in favor of the existence of T-cell–driven inflammation in human hypertension.Download figureDownload PowerPointCardiac Effects of Hyperaldosteronism (page 62)Affecting >11% of the patients referred to specialized hypertension centers, primary aldosteronism (PA) is the most common endocrine cause of high blood pressure. Furthermore, it induces cardiovascular damage in excess of that expected based on the degree of blood pressure elevation. PA is potentially curable with a targeted treatment, but whether normalization of the blood pressure and regression of associated cardiovascular damage could be achieved in the long term remained uncertain. Rossi et al prospectively assigned 180 PA patients to either adrenalectomy (n=110) or medical therapy (n=70), based on whether there was lateralization of aldosterone excess at adrenal vein sampling. Long-term follow-up study with serial echocardiography evaluations showed for the first time in a prospective study that atrial fibrillation was ≈6-fold higher in PA than in essential hypertensive patients. After treatment blood pressure fell comparably in adrenalectomized and medically treated PA, as it did in optimally treated essential hypertensives. Left ventricular (LV) mass index and the rate of LV hypertrophy also fell mainly through LV inward remodeling in PA patients. Notwithstanding this, the rate of LV mass that was disproportionally elevated for cardiac workload and sex in PA subjects unexpectedly increased. While highlighting the cardiovascular consequences of PA patients, these findings underscore the importance of a timely identification of PA to enable reversal of the LV abnormalities and lowering cardiovascular risk.Download figureDownload PowerPoint Previous Back to top Next FiguresReferencesRelatedDetails July 2013Vol 62, Issue 1 Advertisement Article InformationMetrics © 2013 American Heart Association, Inc.https://doi.org/10.1161/HYP.0b013e31829d4408 Originally publishedJuly 1, 2013 PDF download Advertisement

THE COMPLEMENT C1Q TUMOUR NECROSIS FACTOR-RELATED PROTEIN 1 LEVEL IN PATIENTS WITH SLEEP APNOEA AND PRIMARY ALDOSTERONISM

ObjectivesTo discuss the serum level of complement c1q tumour necrosis factor-related protein 1 (CTRP1) and its related factors in patients with sleep apnoea obstructive sleep apnoea (OSA) and primary aldosteronism...

The levels of renin–angiotensin related components are modified in the hippocampus of rats submitted to pilocarpine model of epilepsy

We previously showed that patients with temporal lobe epilepsy (TLE) present an increased expression of angiotensin II (AngII) AT1 and AT2 receptors in the hippocampus, supporting the idea of an upregulation of renin–angiotensin system (RAS) in this disease.This study aimed to verify the relationship between the RAS and TLE during epileptogenesis. Levels of the peptides angiotensin I (AngI), angiotensin II (AngII) and angiotensin 1–7 (Ang 1–7), were detected by HPLC assay. Angiotensin AT1 and AT2 receptors, Mas mRNA receptors and angiotensin converting enzyme (ACE), tonin and neutral endopeptidase (NEP) mRNA were also quantified at the hippocampus of Wistar rats by real time PCR, during acute (n=10), silent (n=10) and chronic (n=10) phases of pilocarpine-induced epilepsy.We observed an increased peptide level of Ang1–7 into acute and silent phases, decreasing importantly (p⩽0.05) in the chronic phase, suggesting that AngI may be converted into Ang 1–7 by NEP, which is present in high levels in these periods.Our results also showed increased peptide level of AngII in the chronic phase of this model. In contraposition, the ACE expression is reduced in all periods. These data suggest that angiotensinogen or AngI may be cleaved to AngII by tonin, which showed increased expression in all phases. We found changes in AT1, AT2 and Mas mRNA receptors levels suggesting that Ang1–7 could act at Mas receptor during the silent period. Herein, we demonstrated for the first time, changes in angiotensin-related peptides, their receptors as well as the releasing enzymes in the hippocampus of rats during pilocarpine-induced epilepsy.