AbstractAngiotensin-converting Enzyme Inhibitors Research Articles

Antihypertensive Therapy by ACEI/ARB Is Associated With Intestinal Flora Alterations and Metabolomic Profiles in Hypertensive Patients.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEI/ARB) are the first-line drugs for the treatment of essential hypertension (HTN), one of the most important risk factors for cardiovascular and cerebrovascular diseases. Intestinal flora and microbial metabolites have been demonstrated to play important roles in blood pressure (BP) regulation and HTN development. However, it remains elusive that intestinal bacteria and metabolites are associated with the protective effects of ACEI/ARB anti-hypertensive drugs against HTN. In this study, we evaluated the effect of ACEI/ARB on gut microbiome and metabolites in patients suffering from HTN. We performed 16S rRNA sequencing and fecal metabolomic analysis of 36 HTN patients placed on ACEI/ARB therapy and 19 newly diagnosed HTN patients with no history of anti-hypertensive treatment. Patients under medication treatment were further classified into well-controlled (n = 24) and poor-controlled (n = 12) groups according to their BP levels. The ACEI/ARB improved the intestinal microbiome of the HTN patients by reducing potentially pathogenic bacteria such as Enterobacter and Klebsiella and increasing beneficial bacteria such as Odoribacter. Moreover, ACEI/ARB therapy was correlated with significant metabolomic changes in the HTN patients, including progressively enhanced inositol from poor-controlled to well-controlled groups. The profiles of gut bacteria were linked to the production of metabolites, and inositol was negatively correlated with Klebsiella, Enterobacter, and Proteobacteria. Our study suggests that ACEI/ARB modulates gut microbial composition and functions and alters microbial metabolites in HTN patients.

Primary prevention of chronic anthracycline cardiotoxicity with ACE inhibitor is temporarily effective in rabbits, but benefits wane in post-treatment follow-up.

Angiotensin-converting enzyme inhibitors (ACEis) have been used to treat anthracycline (ANT)-induced cardiac dysfunction, and they appear beneficial for secondary prevention in high-risk patients. However, it remains unclear whether they truly prevent ANT-induced cardiac damage and provide long-lasting cardioprotection. The present study aimed to examine the cardioprotective effects of perindopril on chronic ANT cardiotoxicity in a rabbit model previously validated with the cardioprotective agent dexrazoxane (DEX) with focus on post-treatment follow-up (FU). Chronic cardiotoxicity was induced by daunorubicin (DAU; 3 mg/kg/week for 10 weeks). Perindopril (0.05 mg/kg/day) was administered before and throughout chronic DAU treatment. After the completion of treatment, significant benefits were observed in perindopril co-treated animals, particularly full prevention of DAU-induced mortality and prevention or significant reductions in cardiac dysfunction, plasma cardiac troponin T (cTnT) levels, morphological damage, and most of the myocardial molecular alterations. However, these benefits significantly waned during 3 weeks of drug-free FU, which was not salvageable by administering a higher perindopril dose. In the longer (10-week) FU period, further worsening of left ventricular function and morphological damage occurred together with heart failure (HF)-related mortality. Continued perindopril treatment in the FU period did not reverse this trend but prevented HF-related mortality and reduced the severity of the progression of cardiac damage. These findings contrasted with the robust long-lasting protection observed previously for DEX in the same model. Hence, in the present study, perindopril provided only temporary control of ANT cardiotoxicity development, which may be associated with the lack of effects on ANT-induced and topoisomerase II β (TOP2B)-dependent DNA damage responses in the heart.

A UPLC-DAD-Based Bio-Screening Assay for the Evaluation of the Angiotensin Converting Enzyme Inhibitory Potential of Plant Extracts and Compounds: Pyrroquinazoline Alkaloids from Adhatoda vasica as a Case Study.

Angiotensin converting enzyme (ACE) plays a crucial role in regulating blood pressure in the human body. Identification of potential ACE inhibitors from medicinal plants supported the idea of repurposing these medicinal plants against hypertension. A method based on ultra-performance liquid chromatography (UPLC) coupled with a diode array detector (DAD) was used for the rapid screening of plant extracts and purified compounds to determine their ACE inhibitory activity. Hippuryl-histidiyl-leucine (HHL) was used as a substrate, which is converted into hippuric acid (HA) by the action of ACE. A calibration curve of the substrate HHL was developed with the linear regression 0.999. The limits of detection and quantification of this method were found to be 0.134 and 0.4061 mM, respectively. Different parameters of ACE inhibitory assay were optimized, including concentration, incubation time and temperature. The ACE inhibition potential of Adhatoda vasica (methanolic-aqueous extract) and its isolated pyrroquinazoline alkaloids, vasicinol (1), vasicine (2) and vasicinone (3) was evaluated. Compounds 1–3 were characterized by various spectroscopic techniques. The IC50 values of vasicinol (1), vasicine (2) and vasicinone (3) were found to be 6.45, 2.60 and 13.49 mM, respectively. Molecular docking studies of compounds 1–3 were also performed. Among these compounds, vasicinol (1) binds as effectively as captopril, a standard drug of ACE inhibition.

Aspecte clinice privind profilul de siguranță al inhibitorilor enzimei de conversie a angiotensinei

Angiotensin converting enzyme (ACE) inhibitors represent a therapeutic class largely used in clinical practice for about 40 years and extensively studied globally. They are mainly recommended for treatment of hypertension and heart failure with reduced ejection fraction, but were also effective in patients with myocardial infarction, stroke and diabetes, proving significant reduction of cardiovascular morbidity and mortality. Besides their undeniable benefits, proven by clinical practice and epidemiological studies, the use of these drugs involves some side effects, the most common being persistent cough and recurrent angioedema. The mechanism of these side effects is the increase in plasma and pulmonary bradykinin levels, as consequence of blocking the angiotensin converting enzyme. ACE-induced cough occurs relatively frequently, usually within the first months of treatment, but sometimes later, leading to multiple investigations and different specialist consultations. ACE-induced angioedema has a lower frequency, is influenced by some individual factors and can occur at any time during the treatment with IECA, making difficult to confirm the diagnosis. The aim of our paper is to present the main current clinical aspects regarding the safety profile of ACE inhibitors, the peculiarities and difficulties of diagnosis, some individual risk factors and the main recommendations for therapeutic approach.

Quantifying Proximal Collecting Tubule Deficiency in Angiotensin-Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker Fetopathy.

Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers (AAs) are used for several indications, with cessation recommended in pregnancy due to toxic effects. AA fetopathy phenotype is similar to renal tubular dysgenesis including reduced proximal convoluted tubules (PCTs). Our study aimed to quantify the reduction of PCTs in fetuses and infants with prenatal exposure to AAs. We identified 5 fetal AA exposure cases that underwent autopsy at our institution between 2011 and 2018 and compared with 5 gestational age-matched controls. Immunohistochemistry with CD10 and epithelial membrane antigen (EMA) was utilized. CD10 and EMA identified a median PCT density of 19.0% ± 12.3% in AA fetopathy patients, significantly less than controls (52.8% ± 4.4%; p < 0.0001). One case with in utero cessation had a PCT density of 34.2% ± 0.2%. Among other AA fetopathy findings, 1 case demonstrated unilateral renal vein thrombosis and 4 had hypocalvaria. We have quantified the reduction in AA fetopathy PCT density, and demonstrated in utero cessation may recover PCT differentiation. Future studies may benefit from calculating PCT percentage as a potential biomarker to correlate with post-natal renal function and maternal factors including medication type, dosage, duration, and time from medication cessation.

Effect of captopril on post-infarction remodelling visualized by light sheet microscopy and echocardiography

Angiotensin converting enzyme inhibitors, among them captopril, improve survival following myocardial infarction (MI). The mechanisms of captopril action remain inadequately understood due to its diverse effects on multiple signalling pathways at different time periods following MI. Here we aimed to establish the role of captopril in late-stage post-MI remodelling. Left anterior descending artery (LAD) ligation or sham surgery was carried out in male C57BL/6J mice. Seven days post-surgery LAD ligated mice were allocated to daily vehicle or captopril treatment continued over four weeks. To provide comprehensive characterization of the changes in mouse heart following MI a 3D light sheet imaging method was established together with automated image analysis workflow. The combination of echocardiography and light sheet imaging enabled to assess cardiac function and the underlying morphological changes. We show that delayed captopril treatment does not affect infarct size but prevents left ventricle dilation and hypertrophy, resulting in improved ejection fraction. Quantification of lectin perfused blood vessels showed improved vascular density in the infarct border zone in captopril treated mice in comparison to vehicle dosed control mice. These results validate the applicability of combined echocardiographic and light sheet assessment of drug mode of action in preclinical cardiovascular research.

ACE2 and ACE: structure-based insights into mechanism, regulation and receptor recognition by SARS-CoV.

Angiotensin converting enzyme (ACE) is well-known for its role in blood pressure regulation via the renin–angiotensin aldosterone system (RAAS) but also functions in fertility, immunity, haematopoiesis and diseases such as obesity, fibrosis and Alzheimer’s dementia. Like ACE, the human homologue ACE2 is also involved in blood pressure regulation and cleaves a range of substrates involved in different physiological processes. Importantly, it is the functional receptor for severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 responsible for the 2020, coronavirus infectious disease 2019 (COVID-19) pandemic. Understanding the interaction between SARS-CoV-2 and ACE2 is crucial for the design of therapies to combat this disease. This review provides a comparative analysis of methodologies and findings to describe how structural biology techniques like X-ray crystallography and cryo-electron microscopy have enabled remarkable discoveries into the structure–function relationship of ACE and ACE2. This, in turn, has enabled the development of ACE inhibitors for the treatment of cardiovascular disease and candidate therapies for the treatment of COVID-19. However, despite these advances the function of ACE homologues in non-human organisms is not yet fully understood. ACE homologues have been discovered in the tissues, body fluids and venom of species from diverse lineages and are known to have important functions in fertility, envenoming and insect–host defence mechanisms. We, therefore, further highlight the need for structural insight into insect and venom ACE homologues for the potential development of novel anti-venoms and insecticides.

A REVIEW ON THE EFFECTIVENESS OF ANGIOTENSIN CONVERTING ENZYME INHIBITORS IN REDUCING CARDIOVASCULAR MORBIDITY AND MORTALITY RISKS

ABSTRACT Angiotensin converting enzyme inhibitors (ACEIs) are long been preferred as a therapeutic choice for cardiovascular disease due to its safe supremacy to overcome the deleterious effects of Angiotensin II, which is a strong vasoconstrictor increases the levels of different growth factors and adhesion molecules. It produces an oxidative stress that accounts for its apoptotic properties. The cardiac myocyte undergoes necrosis induced by angiotensin II and it also activates neurohumoral system in post infarction left ventricular dysfunction patients. ACE inhibitors reduce the production of angiotensin II by endothelial cells. It also simultaneously diminishes the deprivation of bradykinin that results in vasodilation to overcome the effects of angiotensin II by exerting its anti-apoptotic actions. Clinical trials such as SAVE, SOLVD, AIRE and TRACE indicated that the life expectancy can be increase by ACE inhibitors in patients having left ventricular dysfunction. EUROPA study suggested that in all patients of coronary heart diseases, perindopril is a treatment of choice along with other preventive therapies. Evidences of clinical researches supports the usage of ACE inhibitors and showed improve clinical results in patients with primary hypertension, stable coronary artery diseases, stable ischemic diseases with preserved ventricular function or reduced ventricular function, and myocardial infarction.FDA has approved that ACE inhibitors as adjunctive therapy in systolic heart failure, and in patients with a history of myocardial infarction and those having reduced ejection fraction to prevent HF. Perindopril is also approved by FDA for cases of stable coronary artery diseases and it is helpful to reduce the risk of mortality with Myocardial infarction. Key Words: Angiotensin II, Cardiac Dysfunction, Coronary artery disease, Heart Failure, Hypertension

1670-P: Enalapril Maleate, Angiotensin-Converting Enzyme Inhibitor, Suppresses the Expression of the MHC Molecules in Mucosal Cells of the Small Intestine Leading to the Delayed Onset of Autoimmune Type 1 Diabetes Mellitus in NOD Mice

Angiotensin-converting enzyme (ACE) exists in the kidney, lung and small intestine of the NOD mouse (autoimmune type 1 diabetes animal model). ACE changes Angiotensin I to Angiotensin II. ACE exists in the small intestinal epithelial cells and villi, and digests the protein antigen molecules in the small intestine. ACE plays an important role in the antigen presenting process in the mucosal immune system of the duodenum and jejunum. To examine if ACE has a role in the development of type 1 diabetes of the NOD mouse, ACE Inhibitors, enalapril maleate (EM) or captopril (CA) was dissolved in a drinking water at the concentration of 12.5μg/ml and given daily to 28-day-old NOD mice ad libitum (89 females and 70 males in CA, 72 and 52 in EM, 120 and 87 in water control group, respectively). The animals were screened for the development of diabetes twice a week for 7 months and subjected to the Life Table analysis. The incidence of diabetes in our NOD/Kmc colony is 83% in females and 40% in males at 210 days of age. The EM-treated NOD mice showed a significant delay of the onset of diabetes at 120 days of age in comparison with the controls (25% vs. 45% in females, P=0.002; 0% vs. 8% in males, P=0.037). The CA treatment was ineffective to delay the onset of diabetes. The histological examination of the pancreata showed that the EM-treated females had more islets without lymphocytic infiltration than the water-control females (mean number of undamaged islets±SD: 11.1±8.5 in EM vs. 1.9±2.5 in Control, P=0.009). The undamaged islets weighed 0.772±0.383 in EM and 0.441±0.386 in water-control (mg: mean±SE). The mRNA expression of MHC K and A genes was suppressed in the duodenum and jejunum of the NOD mice by EM- or CA-water for 14 days. Flow cytometric analysis showed suppression of the MHC K and I-A expression in the pancreatic lymphocytes of the EM- and CA-treated mice in comparison with the control mice. Disclosure M. Hattori: None. A. Ueda: None. R. Katoh: None. M. Hirai: None. A. Noda: None. K. Mayanagi: None. Y. Furuichi: None. K. Hattori: None. T. Lund: None. K. Kobayashi: None. Y. Nakamura: None.

Effect of Combination ACEI (Angiotensin Converting Enzyme Inhibitor) and Diuretics on Potassium Levels of Congestive Heart Failure Patients

ACEI (Angiotensin Converting Enzyme Inhibitors) and diuretics are now the treatment options for heart failure patients. However, the use of ACEI and diuretics can cause potassium balance disorders. This study aimed to evaluate the use of ACEI and diuretics combinations on potassium levels in patients with congestive heart failure. This study used analytical research and sampling, done in total sampling. Samples were divided into 2 groups, group with combination of ACEI, furosemide and spironolactone along with combination group of ACEI and furosemide. Total samples obtained were 38 patients. The results showed that the averaged potassium levels in combinations of ACEI, furosemide and spironolactone before treatment were 3.95mmol/L and after treatment were 3.85 mmol/L (p = 0.061), the averaged potassium levels before receiving therapy were 4.20 mmol/L and after receiving 4.14 mmol/L therapy (p = 0.070) in combinations of ACEI and furosemide. In combinations of ACEI, furosemide and spironolactone, of a total of 25 patients, hypokalemia was found in 6 patients (24%), normal in 19 patients (76%) and 0 patient had hyperkalemia (0%), while combinations of ACEI and furosemide, of a total of 13 patients, all patients have normal potassium levels. So it can be concluded that there were no significant changes between potassium levels before and after receiving therapy of ACEI and diuretics combination.

DETERMINATION OF IN VITRO OUTLET OF LIZINOPRIL CONTAINING MEDICAL PREPARATION ”LIZINOCOR” AND ITS ANALOGUE USING METHOD OF HIGHPERFORMANCE LIQUID CHROMATOGRAPHY

ACE Inhibitors represent the first class of anti hypertensive agents that was designed and developed on the basis of a well-defined physiopathol ogical axis of arterial hypertension, a vascular disorder that is now becoming one of the major causes of morbidity/mortality, not only in developed societies but also in the highly populated developing countries. An angiotensin-converting enzyme (ACE) inhibitor, the carboxylalkyl compounds derivated lizinopril is apharmaceutical drug, used primarily for the treatment of hypertension (elevated blood pressure) and congestive heart failure. Purpose of investigation was – comparison of in vitro outlet of 5 mg tablets of ”Lizinocor” containing Lizinopril , produced by the Georgian pharmaceutical company “GMP” and its analogue ”Zestril” using method of high-performance liquid chromatography. According to the received results average percent quantity outlet of ”lizinocor” is 97,65 %, ”Zestril” – 95, 88%;. Inclination in comparison with Zestril is 1,85 %, (norm ± 5 %). ”Lizinocor” 5 mg tablets containing Lizinopril produced by the Georgian pharmaceutical company ”GMP” are characterized by good outlet quality.

Structural basis for the C-domain-selective angiotensin-converting enzyme inhibition by bradykinin-potentiating peptide b (BPPb).

Angiotensin-converting enzyme (ACE) is a zinc metalloprotease best known for its role in blood pressure regulation. ACE consists of two homologous catalytic domains, the N- and C-domain, that display distinct but overlapping catalytic functions in vivo owing to subtle differences in substrate specificity. While current generation ACE inhibitors target both ACE domains, domain-selective ACE inhibitors may be clinically advantageous, either reducing side effects or having utility in new indications. Here, we used site-directed mutagenesis, an ACE chimera and X-ray crystallography to unveil the molecular basis for C-domain-selective ACE inhibition by the bradykinin-potentiating peptide b (BPPb), naturally present in Brazilian pit viper venom. We present the BPPb N-domain structure in comparison with the previously reported BPPb C-domain structure and highlight key differences in peptide interactions with the S4 to S9 subsites. This suggests the involvement of these subsites in conferring C-domain-selective BPPb binding, in agreement with the mutagenesis results where unique residues governing differences in active site exposure, lid structure and dynamics between the two domains were the major drivers for C-domain-selective BPPb binding. Mere disruption of BPPb interactions with unique S2 and S4 subsite residues, which synergistically assist in BPPb binding, was insufficient to abolish C-domain selectivity. The combination of unique S9-S4 and S2' subsite C-domain residues was required for the favourable entry, orientation and thus, selective binding of the peptide. This emphasizes the need to consider factors other than direct protein-inhibitor interactions to guide the design of domain-selective ACE inhibitors, especially in the case of larger peptides.

Angiotensin-converting Enzyme Inhibitors-induced Angioedema

Abstract Angiotensin-converting enzyme inhibitors (ACEI) are widely used drugs nowadays in treating patients diagnosed with cardiovascular disorders. We present two consecutive cases of acquired angioedema caused by the administration of enalapril and lisinopril in patients with indication for ACE-inhibitors therapy. Rigorous follow-up of side effects of ACEI is required, due to these possible life-threatening adverse reactions.

The Evaluation of Angiotensin-Converting Enzyme Inhibitors in Renal Elimination with Selected Molecular Descriptors

Abstract Angiotensin-converting enzyme (ACE) inhibitors modulate the function of the renin-angiotensin-aldosterone system, and they are commonly prescribed antihypertensive drugs especially in patients with renal failure. In this study, the relationships between several molecular properties of eight ACE inhibitors (enalapril, quinapril, fosinopril, ramipril, benazepril, perindopril, moexipril, trandolapril) and their renal elimination data, from relevant literature, were investigated. The ’molecular descriptors of the ACE inhibitors, which included aqueous solubility data (logS); an electronic descriptor, polar surface area (PSA);, a constitutional parameter, molecular mass (Mr); and a geometric descriptor, volume value (Vol), as well as lipophilicity descriptors (logP values), were calculated using different software packages. Simple linear regression analysis showed the best correlation between renal elimination data and lipophilicity descriptor AClogP values (R2 = 0.5742). In the next stage of the study, multiple linear regression was applied to assess a higher correlation between the ACE inhibitors’ renal elimination data and lipophilicity, AClogP, with one additional descriptor as an independent variable. Good correlations were established between renal elimination data from the literature and the AClogP lipophilicity descriptor using the constitutional parameter (molecular mass (R2 = 0.7425)) or the geometric descriptor (volume value (R2 = 0.7224)) as an independent variable. The application of computed molecular descriptors in evaluating drug elimination is of great importance in drug research.

Angioedema Due to ACE Inhibitors

Angiotensin-converting enzyme inhibitors (ACEIs) are widely used for treatment of hypertension, congestive heart failure, and cardiovascular and renal protection in patients with heart failure, among others. Angioedema is a rare but potentially fatal adverse event (ACEI-AAE), whose prevalence is under 0.5 % among patients taking ACEIs and is higher among African Americans and female patients. There is no biomarker that allows diagnosis of ACEI-AAE, and the diagnosis is based on clinical history and the intake of ACEIs. Differential diagnosis with other causes of edema/angioedema must be considered. Recent classifications of angioedema can be of great help in the diagnosis process. The management of ACEI-induced angioedema involves the withdrawal of the causative drug and the treatment of the acute angioedema with different off-label drugs (icatibant, plasma-derived human C1 inhibitor protein). This manuscript will review the epidemiology, pathophysiology, genetics, clinical symptoms, diagnosis, and treatment of ACEI-AAE.

Isolation and Characterization of a New Angiotensin-converting Enzyme Inhibitory Peptide from Heterobronchus bidorsalis

Angiotensin converting enzyme (ACE) plays an important physiological role in the regulation of blood pressure by converting angiotensin I to angiotensin II, a potent vasoconstrictor; hence, its inhibition is a major target in the prevention and treatment of hypertension. In this study a novel ACE inhibitory peptide from Heterobronchus bidorsalis (cat fish) was isolated, purified and characterized. The peptide was purified by ammonium sulphate precipitation, dialysis and gel filtration chromatography (sephadex G-50). The amino acid sequence of the seventeen amino acid peptide was found to be KHRDTSEPGACVMILYF with a final inhibitory activity of 0.07 μmol/ml and a purification fold of 2.93 having a percentage yield of 34 %. The peptide had an optimum temperature and pH of 37°C and 8.3, respectively. The ACE inhibitory activity of the peptide reduced in the presence of sodium, calcium, magnesium, and potassium ions, while EDTA increased it when compared to the control. Treatment with trypsin also increased the inhibitory activity of the peptide. The peptide exhibited a non-competitive-type of inhibition, indicating that it binds to a site other than the active site. In conclusion, peptides from H. bidorsalis may be promising ACE inhibitors that can serve as nutraceuticals or drugs for blood pressure regulation in hypertensive patients.

A prospective study of frequency and characteristics of cough during ACE inhibitor treatment

Angiotensin converting enzyme (ACE) inhibitors are reportedly effective, and positively indicated in patients with chronic heart failure with decreased contractility, after myocardial infarction, after cerebrovascular disorders, and in those with chronic kidney disease. However, the biggest challenge to continuous use of ACE inhibitors is the adverse reaction of cough. Accordingly, in the present study, we investigated the present state and characteristics of ACE inhibitor-induced cough in patients with essential hypertension currently being treated with an ACE inhibitor for an average of 18 months, who could be regularly checked for cough. Subjects in this study were 176 patients overall (mean age 67 ± 11 years old), 90 men and 86 women. The adverse reaction of cough was observed in 20% of patients, and more frequently in women than in men. However, in 26 of the patients with cough, the cough either resolved naturally or completely disappeared while the treatment continued, after which patients could continue taking the medication. Specifically, ACE inhibitor treatment was eventually discontinued due to cough in 5.1% of patients. Cough occurred less frequently with concomitant calcium antagonists or diuretics than with ACE inhibitor monotherapy. Cough as an adverse reaction occurred at a low frequency when medication was taken at bedtime. We considered a number of measures to counteract cough, then in addition to starting the ACE inhibitor treatment as early as possible, it is important to devise ways for the ACE inhibitor treatment to be continued for as long as possible, through the adept use of these measures.

Preconception and pregnancy management of women with diabetic nephropathy on angiotensin converting enzyme inhibitors

Angiotensin converting enzyme (ACE) inhibitors are the mainstay of treatment for diabetic nephropathy to slow progression of disease. Diabetic women of childbearing age with nephropathy should be treated with ACE inhibitors as per guidelines in the pre-pregnancy period. ACE inhibitor use and exposure in the first trimester is controversial and requires counselling pre-pregnancy regarding the risks and benefits of use up to the first trimester, as well as the need to stop ACE inhibitors prior to the second trimester. Current evidence does not suggest that ACE inhibitors in the first trimester are associated with a greater risk of fetal malformations when compared to other antihypertensives. This topic is reviewed in depth, along with blood pressure targets in pregnant women with diabetic proteinuric disease, evidence for prevention of pre-eclampsia, self-monitoring of blood pressures at home in the latter half of pregnancy and the signs and symptoms of pre-eclampsia, proteinuria evolution in pregnancy, renal function prognosis, and restarting ACE inhibitors when breast feeding in the post-partum period.

Angiotensin-converting enzyme inhibitors and beta-blockers in the treatment of symptomatic heart failure

Angiotensin-converting enzyme inhibitors and beta-blockers are the main therapies used in the treatment of symptomatic systolic heart failure. In practice, those two groups are usually used simultaneously because of their complementary mechanism and effect. Current guidelines limit the list of recommended drugs to those, that were successfully tested in large randomised trials. In addition, they provide optimal dosage that was used in these studies. This article presents a summary of the current recommendations in this topic.

Role of Ace Inhibitors In Atherosclerosis

Angiotensin converting enzyme (ACE) inhibitors are an important class of antihypertensive drugs which have been used in the treatment of cardiovascular diseases where hypertension is the main risk factor. In hypertensive patients, it has been observed that there is formation of atherosclerotic plaques.Circulating and local renin angiotensin system (RAS) have been involved in atherosclerotic process on the basis of experimental data showing the presence and specific actions of the components of this system in the vascular wall particularly, angiotensin II which participate in atherogenesis. ACE inhibitors prevent angiotensin II induced vascular proliferation and thereby thereby suppress the development of atherosclerosis in animals. It is also seen that blood pressure effects of ACE inhibitors could play a role in the antiatherosclerotic effect of these drugs. Other mechanisms involved could be blockade of the renin angiotensin system on sympathetic nervous activity, regulation of vascular growth factors and insulin sensitivity. Oxidative stress also plays an important part in the pathogenesis of hypertension and atherosclerosis. ACE inhibitors have been shown to have anti-oxidant activity and by their antihypertensive action , they can prevent atherosclerosis also. In this review, maximum information related to ACE inhibitors, hypertension and atherosclerosis has been compiled for the benefit of physicians and patients.