ACE Inhibitors

ACE inhibitors have been shown to be effective in reducing the morbidity and mortality of patients with left ventricular systolic dysfunction, but their application to clinical practice in this situation is still limited. In part, the failure to prescribe an ACE inhibitor to a patient with left ventricular systolic dysfunction is due to perceptions regarding their side effects, such as cough and renal dysfunction. Relatively few patients with left ventricular systolic dysfunction and a serum creatinine =2 mg/dl receive an ACE inhibitor in clinical practice. In this situation one should consider an agent such as fosinopril, which is metabolized by the liver as well as secreted by the kidney. In patients with moderate renal dysfunction, fosinopril has been well tolerated without an increase in serum creatinine. In patients who develope cough due to an ACE inhibitor, consideration should be given to an angiotensin II type 1 receptor blocking agent, such as losartan. The relative safety...

We questioned the superiority of angiotensin converting enzyme (ACE) inhibitors to beta blocking drugs with regard to renal function outcome in patients with mild to moderate renal insufficiency and normal to moderately elevated blood pressure (BP). We therefore studied 89 patients in a prospective double-blind randomized trial comparing the effect of enalapril and atenolol on the slope of glomerular filtration rate (GFR). Mean baseline GFR was 53 +/- 20 ml/min, untreated BP 152 +/- 20 mm Hg systolic and 90 +/- 11 mm Hg diastolic and median proteinuria 0.6 g/24 hr (interquartile range 0.0 to 2.5). After a run-in period without antihypertensives, the test drug was titrated to lower diastolic BP to a predefined goal of 10 mm Hg below baseline and/or below 95 mm Hg. The median follow up was 3.9 years. Antihypertensive therapy resulted in a comparable decrease of BP in both study groups. Filtration fraction and proteinuria decreased in both groups. The slope of GFR over time was not different between both groups (-1.39 +/- 2.82 and -1.97 +/- 3.38 ml/min/year on atenolol and enalapril, respectively). In multiple regression analysis a higher baseline GFR, a greater decrease in GFR and in proteinuria during titration and a lower proteinuria during follow up were independently related to a better GFR slope. We conclude that the use of ACE inhibitors is not imperative in all patients with non-diabetic nephropathy.

Angiotensin-converting enzyme (ACE) inhibitors reduce mortality, the development of remodeling, left ventricular (LV) dysfunction, and ischemic events, both when administered alone as long-term treatment in patients with impaired LV function and/or heart failure (HF) and as short-term treatment, early after acute myocardial infarction (AMI) and/or HF. The few data available on the use of ACE inhibitors in the elderly after AMI are conflicting. Nothing is known about the effects of ACE inhibitors in elderly postinfarction patients with preserved LV function: these patients have a remarkable medium- to long-term mortality and HF incidence after infarction. The aim of this study is to evaluate, in patients with AMI aged =65 years, the effects of Perindopril on the combined outcome of death, hospitalization for HF, and heart remodeling, considered to be a =8% increase in LV end-diastolic volume (LVEDV). Secondary objectives include the same factors listed in the primary end points but c...

Hipertensi adalah salah satu penyakit dengan angka kesakitan dan kematian yang terus meningkat, termasuk di Indonesia. Dalam mengatasi hipertensi obat-obatan seperti ACE inhibitor berperan dalam menurunkan tekanan darah diastol dan sistol, namun tanaman obat seperti ekstrak buah hawthorn, buah zaitun (Olea europaea L.), Hibiscus Sabdariffa, Allium Sativum dan Allium Cepa juga memiliki efek sebagai antihipertensi dengan harga yang relatif murah, mudah didapat, efek samping yang lebih rendah dibandingkan dengan obat sintesis atau kimia lainnya. Review jurnal ini ditujukan untuk mengetahui berbagai tanaman obat yang memiliki aktivitas hipertensi dan berpengaruh terhadap ekspresi gen reseptor hipertensi ACE1 dan ACE2. Penelusuran referensi dilakukan melalui database PubMed, Science Direct, dan Google Scholar, dengan kata kunci “Medicinal Plant”, “Gene expression”, “Angiotensin Converting Enzyme 1”, “Angiotensin Converting Enzyme 2”, dan“Antihypertension”. Tanaman obat digunakan sebagai ...

Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, is expressed as a type-1 membrane glycoprotein on the surface of different cells, including endothelial cells of the heart. We hypothesized that the local conformation and, therefore, the properties of heart ACE could differ from lung ACE due to different microenvironment in these organs. We performed ACE phenotyping (ACE levels, conformation and kinetic characteristics) in the human heart and compared it with that in the lung. ACE activity in heart tissues was 10-15 lower than that in lung. Various ACE effectors, LMW endogenous ACE inhibitors and HMW ACE-binding partners, were shown to be present in both heart and lung tissues. "Conformational fingerprint" of heart ACE (i.e., the pattern of 17 mAbs binding to different epitopes on the ACE surface) significantly differed from that of lung ACE, which reflects differences in the loca...

Objectives To investigate the effect of ACE inhibitors (ACEi) on the incidence of scleroderma renal crisis (SRC) when given prior to SRC in the prospectively collected cohort from the European Scleroderma Trial and Research Group (EUSTAR). Methods SSc patients without prior SRC and at least one follow-up visit were included and analyzed regarding SRC, arterial hypertension, and medication focusing on antihypertensive medication and glucocorticoids (GC). Results Out of 14,524 patients in the database, we identified 7648 patients with at least one follow-up. In 27,450 person-years (py), 102 patients developed SRC representing an incidence of 3.72 (3.06–4.51) per 1000 py. In a multivariable time-to-event analysis adjusted for age, sex, disease severity, and onset, 88 of 6521 patients developed SRC. The use of ACEi displayed an increased risk for the development of SRC with a hazard ratio (HR) of 2.55 (95% confidence interval (CI) 1.65–3.95). Adjusting for arterial hypertension resulted...

Inflammatory bowel diseases (IBDs) are chronic disorders of the gastrointestinal tract, which manifest in recurring gastrointestinal inflammation. The current treatment options of IBD are not curative and are lacking in aspects like prevention of fibrosis. New treatment options are needed to fulfil the unmet needs and provide alternatives to drugs with resistances and side effects. Drugs targeting the renin–angiotensin system (RAS), besides being antihypertensive, also possess anti‐inflammatory and antifibrotic properties and could offer an inexpensive alternative to control inflammation and fibrosis in the gut. RAS inhibitors have been effective in preventing and alleviating colitis in preclinical studies, but available human data are still sparse. This review outlines the pathophysiological functions of RAS in the gut and summarizes preclinical studies utilizing pharmacological RAS inhibitors in the treatment of experimental colitis. We discuss the alterations in intestinal RAS an...

Background: There are no previous Spanish guidelines or consensus statements on bradykinin-induced angioedema. Aim: To draft a consensus statement on the management and treatment of angioedema mediated by bradykinin in light of currently available scientific evidence and the experience of experts. This statement will serve as a guideline to health professionals. Methods: The consensus was led by the Spanish Study Group on Bradykinin-Induced Angioedema, a working group of the Spanish Society of Allergology and Clinical Immunology. A review was conducted of scientific papers on different types of bradykinin-induced angioedema (hereditary and acquired angioedema due to C1 inhibitor deficiency, hereditary angioedema related to estrogens, angioedema induced by angiotensin-converting enzyme inhibitors). Several discussion meetings were held to reach the consensus. Results: Treatment approaches are discussed, and the consensus reached is described. Specific situations are addressed, namely, pregnancy, contraception, travelling, blood donation, and organ transplantation. Conclusions: A review of and consensus on treatment of bradykinin-induced angioedema is presented.

Background: There are no Spanish guidelines or consensus statement on bradykinin-induced angioedema. Aim: To review the pathophysiology, genetics, and clinical symptoms of the different types of bradykinin-induced angioedema and to draft a consensus statement in light of currently available scientific evidence and the experience of experts. This statement will serve as a guideline to health professionals. Methods: The consensus was led by the Spanish Study Group on Bradykinin-Induced Angioedema (SGBA), a working group of the Spanish Society of Allergology and Clinical Immunology. A review was conducted of scientific papers on different types of bradykinin-induced angioedema (hereditary and acquired angioedema due to C1 inhibitor deficiency, hereditary angioedema related to estrogens, angioedema induced by angiotensin-converting enzyme inhibitors). Several discussion meetings of the SGBA were held in Madrid to reach the consensus. Results: The pathophysiology, genetics, and clinical symptoms of the different types of angioedema are reviewed. Diagnostic approaches are discussed and the consensus reached is described. Conclusions: A review of bradykinin-induced angioedema and a consensus on diagnosis are presented.

Objectives To investigate the effect of ACE inhibitors (ACEi) on the incidence of scleroderma renal crisis (SRC) when given prior to SRC in the prospectively collected cohort from the European Scleroderma Trial and Research Group (EUSTAR). Methods SSc patients without prior SRC and at least one follow-up visit were included and analyzed regarding SRC, arterial hypertension, and medication focusing on antihypertensive medication and glucocorticoids (GC). Results Out of 14,524 patients in the database, we identified 7648 patients with at least one follow-up. In 27,450 person-years (py), 102 patients developed SRC representing an incidence of 3.72 (3.06–4.51) per 1000 py. In a multivariable time-to-event analysis adjusted for age, sex, disease severity, and onset, 88 of 6521 patients developed SRC. The use of ACEi displayed an increased risk for the development of SRC with a hazard ratio (HR) of 2.55 (95% confidence interval (CI) 1.65–3.95). Adjusting for arterial hypertension resulted...

У роботі представлено результати дослідження співвідношення активності окисної та відновної систем крові щурів за умов гострого перитоніту. Встановлено, що поєднання останнього з цукровим діабетом та ураженням печінки і нирок має характерні закономірності - спотворення окисно-відновних процесів та швидкий розвиток недостатності антиоксидантних систем

The potential of targeting the Renin-Angiotensin-Aldosterone System (RAAS) as a treatment for the coronavirus disease 2019 (COVID-19) is currently under investigation. One way to combat this disease involves the repurposing of angiotensin receptor blockers (ARBs), which are antihypertensive drugs, because they bind to angiotensin-converting enzyme 2 (ACE2), which in turn interacts with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. However, there has been no in silico analysis of the potential toxicity risks associated with the use of these drugs for the treatment of COVID-19. To address this, a network-based bioinformatics methodology was used to investigate the potential side effects of known Food and Drug Administration (FDA)-approved antihypertensive drugs, Sartans. This involved identifying the human proteins targeted by these drugs, their first neighbors, and any drugs that bind to them using publicly available experimentally supported data, an...

The objective: to evaluate the effect of Tivor-L (20 mg levocarnitine + 42 mg arginine hydrochloride, Yuriya-Pharm) on AGEs, galectin-3, MMP-2,9 serum level, cardiac haemodynamics and endothelial function in patients with post infarction HFpEF.Materials and methods. All individuals (35) included aged 40 to 80 years, 23 (66%) males and 12 (34%) females were diagnosed with (HFpEF) according to ESC guidelines (2016). First (1-st ) group (n=15) pts with postinfarction HFpEF treated with Tivor-L in addition to standard treatment for Chronic heart failure (CHF). Second (2nd) group (n=20) – pts with postinfarction HFpEF with standard treatment for CHF without Tivor-L. All the patients included in 1st group got Tivor-L intravenously daily for 10 days in addition to the conventional therapy. General biochemical blood analysis, complete blood count and glomerular filtration rate, MMP-2, MMP-9, galectin-3 and AGEs serum levels were determined before and after treatment.Results. Mean galectin-3...

Мета дослідження – визначити особливості добового ритму артеріального тиску у дітей із вазовагальними синкопе за допомогою методу добового моніторування артеріального тиску. Матеріали та методи. Основну групу склали 65 дітей віком 8–17 років із діагнозом вазовагального синкопе. До контрольної групи увійшла 41 здорова дитина аналогічного віку без ознак гострих чи хронічних захворювань. Для діагностики вазовагальних синкопе використовували критерії Європейської асоціації кардіологів 2018 р. Усім обстеженим проводили добовий моніторинг артеріального тиску за допомогою осцилометричного монітора BAT41-2 (Україна) протягом 24 год за умов звичайного функціонування.    Результати дослідження та їх обговорення. Діти двох груп були зіставними за результатами демографічних та клінічних показників, що дозволило нівелювати вплив статі, віку, дефіциту та надлишкової маси тіла й ожиріння на показники артеріального тиску. Жодних відмінностей у поширеності денної та нічної систолічної й діастолічної...

Objectives To investigate the effect of ACE inhibitors (ACEi) on the incidence of scleroderma renal crisis (SRC) when given prior to SRC in the prospectively collected cohort from the European Scleroderma Trial and Research Group (EUSTAR). Methods SSc patients without prior SRC and at least one follow-up visit were included and analyzed regarding SRC, arterial hypertension, and medication focusing on antihypertensive medication and glucocorticoids (GC). Results Out of 14,524 patients in the database, we identified 7648 patients with at least one follow-up. In 27,450 person-years (py), 102 patients developed SRC representing an incidence of 3.72 (3.06–4.51) per 1000 py. In a multivariable time-to-event analysis adjusted for age, sex, disease severity, and onset, 88 of 6521 patients developed SRC. The use of ACEi displayed an increased risk for the development of SRC with a hazard ratio (HR) of 2.55 (95% confidence interval (CI) 1.65–3.95). Adjusting for arterial hypertension resulted...

In order to investigate whether the angiotensin converting enzyme-inhibitory tomato extract FruitflowR would lower blood pressure after consumption, we conducted a randomised, doubleblinded, placebo-controlled human intervention study, involving 12 pre-hypertensive people in a crossover design. Consuming a single dose of 150mg FruitflowR resulted in a significant reduction in 24-hour average blood pressure as well as average wake-period and sleep-period SBP, compared to placebo. Other parameters related to blood pressure, such as 24-hour average mean arterial pressure, pulse pressure, heart rate, central aortic systolic pressure and radial augmentation index were also reduced. In addition, the platelet aggregation response to ADP, measured 24hours after consuming FruitflowR , fell significantly compared to baseline, and compared to placebo. This pilot study clearly shows the beneficial effects of FruitflowR on two important cardiovascular risk factors, high blood pressure and platel...

The incidence of renal replacement therapy varies across countries. However, little is known about the epidemiology of chronic kidney disease (CKD) outcomes. Here we describe progression and mortality risk of patients with CKD but not on renal replacement therapy at outpatient nephrology clinics across Europe using individual data from nine CKD cohorts participating in the European CKD Burden Consortium. A joint model assessed the mean change in estimated glomerular filtration rate (eGFR) and mortality risk simultaneously, thereby accounting for mortality risk when estimating eGFR decline and vice versa, while also correcting for the measurement error in eGFR. Results were adjusted for important risk factors (baseline eGFR, age, sex, albuminuria, primary renal disease, diabetes, hypertension, obesity and smoking) in 27,771 patients from five countries. The adjusted mean annual eGFR decline varied from 0.77 (95% confidence interval 0.45, 1.08) ml/min/1.73m in the Belgium cohort to 2....

Objectives To investigate the effect of ACE inhibitors (ACEi) on the incidence of scleroderma renal crisis (SRC) when given prior to SRC in the prospectively collected cohort from the European Scleroderma Trial and Research Group (EUSTAR). Methods SSc patients without prior SRC and at least one follow-up visit were included and analyzed regarding SRC, arterial hypertension, and medication focusing on antihypertensive medication and glucocorticoids (GC). Results Out of 14,524 patients in the database, we identified 7648 patients with at least one follow-up. In 27,450 person-years (py), 102 patients developed SRC representing an incidence of 3.72 (3.06–4.51) per 1000 py. In a multivariable time-to-event analysis adjusted for age, sex, disease severity, and onset, 88 of 6521 patients developed SRC. The use of ACEi displayed an increased risk for the development of SRC with a hazard ratio (HR) of 2.55 (95% confidence interval (CI) 1.65–3.95). Adjusting for arterial hypertension resulted...

A hemp seed protein isolate, prepared from defatted hemp seed meals by alkaline solubilization/acid precipitation, was subjected to extensive chemical hydrolysis under acid conditions (6 M HCl). The resulting hydrolysate was fractionated by semipreparative RP-HPLC, and the purified fractions were tested as inhibitors of angiotensin converting enzyme (ACE). Mono- and bidimensional NMR experiments and LC-MS analyses led to the identification of four potentially bioactive peptides, i.e. GVLY, IEE, LGV, and RVR. They were prepared by solid-phase synthesis, and tested for ACE-inhibitory activity. The IC50 values were GVLY 16 ± 1.5 μM, LGV 145 ± 13 μM, and RVR 526 ± 33 μM, confirming that hemp seed may be a valuable source of hypotensive peptides.

Although improved during the past few years, high blood pressure control still remains an unmet goal of antihypertensive drug treatment. Among different antihypertensive agents, calcium channel blockers (CCBs), either as monotherapy or in combination with other drugs are recommended by several guidelines for initiation and maintenance of antihypertensive treatment. The HYT-HYperTension survey, carried out in Turkey was aimed to assess (a) blood pressure control in hypertensive patients under treatment with dihydropyridine CCBs, either as monotherapy or in combination with other drugs and (b) the prevalence of blood pressure control in subgroups of patients with cardiovascular risk factors (previous cardiovascular disease, diabetes, renal disease, isolated systolic hypertension, visceral obesity, overweight, current smoking habit). More than 7000 hypertensive patients (60.0 % men, mean age 61.2 ± 11.5 years), routinely visited by either a specialist or a non-specialist physician in t...

The potential of targeting the Renin-Angiotensin-Aldosterone System (RAAS) as a treatment for the coronavirus disease 2019 (COVID-19) is currently under investigation. One way to combat this disease involves the repurposing of angiotensin receptor blockers (ARBs), which are antihypertensive drugs, because they bind to angiotensin-converting enzyme 2 (ACE2), which in turn interacts with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. However, there has been no in silico analysis of the potential toxicity risks associated with the use of these drugs for the treatment of COVID-19. To address this, a network-based bioinformatics methodology was used to investigate the potential side effects of known Food and Drug Administration (FDA)-approved antihypertensive drugs, Sartans. This involved identifying the human proteins targeted by these drugs, their first neighbors, and any drugs that bind to them using publicly available experimentally supported data, an...