Effect Of Angiotensin-converting Enzyme Research Articles

Effects of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use on cancer therapy-related cardiac dysfunction: a meta-analysis of randomized controlled trials.

Angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) may attenuate cancer therapy-related cardiac dysfunction (CTRCD). However, results of the previous studies were not consistent. We performed a meta-analysis to evaluate the influence of ACEI/ARB on CTRCD. Randomized controlled trials (RCTs) were obtained by searching of PubMed, Embase, and Cochrane's Library databases. A random-effect model was used to pool the results. Nine RCTs with 1095 cancer patients that underwent chemotherapy with anthracycline and/or trastuzumab were included. Using of ACEI/ARB significantly preserved left ventricular ejection fraction (LVEF, weighed mean difference = 4.24%, p = 0.002) compared with controls. Subgroup analyses showed that the benefits of ACEI/ARB on LVEF following chemotherapy were consistent and independent of study characteristics including study design, sample size, cancer type, chemotherapy protocols, preventative medications of ACEI or ARB, methods for LVEF measurement, and follow-up durations. The benefits on LVEF following chemotherapy were more remarkable in studies using ACEI and followed ≤ 12months (p for subgroup difference = 0.04 and 0.02). Use of ACEI/ARB did not significantly reduce the risk of cardiotoxicity events (risk ratio [RR] = 0.63, p = 0.22) but increased the risk of hypotension in these patients (RR = 3.94, p = 0.008). These results indicated that using of ACEI/ARB may moderately attenuate CTRCD following chemotherapy with anthracycline and/or trastuzumab. Large-scale RCTs are needed to evaluate whether the benefits of ACEI/ARB on LVEF are clinically relevant.

Pharmacogenetic study of ACE, AGT, CYP11B1, CYP11B2 and eNOS gene variants in hypertensive patients from Faisalabad, Pakistan.

To investigate the association of genetic variants of renin angiotensin aldosterone system, endothelial nitric oxide synthase and 11-beta-hydroxylase genes, and the drug efficacy of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker. This two time-point study was conducted from April to November 2016 at Allied Hospital, Faisalabad and National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, and comprised of hypertensive patients taking angiotensin-converting enzyme inhibitor and angiotensin receptor blocker who were followed up for 12 weeks. Baseline and follow-up clinical and biochemical parameters were measured for all patients. Total 11 polymorphisms were genotyped by polymerase chain reaction, polymerase chain reaction-restriction fragment length polymorphism and amplification-refractory mutation system-polymerase chain reaction assays. Data was divided into baseline and follow-up groups, while the latter group was further divided into responding and non-responding subgroups on the basis of patient response to angiotensin-converting enzyme inhibitor and angiotensin receptor blocker drugs. Data was analysed using SPSS 20. Of the 45 patients, 25(55.5%) were females and 20(44.5%) were males. There was a significant reduction in the systolic blood pressure (p=0.004) and low-density lipoprotein cholesterol (p<0.001) from the baseline to the follow-up. Systolic blood pressure was significantly reduced in the responding group (p=0.003), while diastolic blood pressure (p=0.121) was not significantly different. There was no effect of angiotensin-converting enzyme, angiotensinogen, 11-beta-hydroxylase, aldosterone synthase and endothelial nitric oxide synthase gene polymorphisms on angiotensin converting enzyme inhibitor and angiotensin receptor blocker efficacy. Inter-individual response to angiotensin converting enzyme inhibitor and angiotensin receptor blocker was found to be independent of genetic polymorphisms in renin angiotensin aldosterone system, endothelial nitric oxide synthase and 11-beta-hydroxylase genes.

ACE2 exhibits protective effects against LPS-induced acute lung injury in mice by inhibiting the LPS-TLR4 pathway

This study aimed to investigate the protective effect of angiotensin converting enzyme 2 (ACE2) on lipopolysaccharide (LPS)-induced acute lung injury (ALI). After generating ALI mouse models by injecting LPS, the levels of ACE2, inflammatory factors, and downstream proteins of the LPS-TLR4 pathway were analyzed. LPS-challenged BEAS-2B cells were established in vitro. Next, a eukaryotic expression vector, pm-ACE2, was constructed and validated. Challenged cells were transfected with pm-ACE2 containing enhanced green fluorescent protein, or they were treated with D-Ala-Ang-(1-7), angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB) and the LPS-TLR4 pathway inhibitor dimethyl fumarate (DMF) for analysis of how the above factors contribute to ACE2 regulation. Expression of renin, Ang II, ACE and angiotensin II type 1 receptor (AT1R) was subsequently assessed. In the ALI model, mice exhibited decreased expression of ACE2, lung pathological injury, inflammatory injury, and abnormal activation of the LPS-TLR4 pathway. LPS-challenged BEAS-2B cells demonstrated upregulated expression of renin, Ang II, ACE and AT1R. After injection of ACE2, lung function and lung pathological injury were significantly improved, and that effect was accompanied by attenuated inflammation, and inactivation of the LPS-TLR4 pathway. Cell studies showed similar results. The above observations were further enhanced when there was a combined treatment with DMF and pm-ACE2. D-Ala-Ang-(1-7) treatment attenuated the protective effect of ACE2, while ACEI and ARB treatment alleviated LPS-induced pneumonic injury. In conclusion, ACE2 was expressed at low levels in response to LPS-induced ALI. Overexpression of ACE2 regulates the ACE2/Ang-(1-7)/Mas and ACE/Ang II/AT1 axes to maintain dynamic balance of the renin-angiotensin system, and attenuate inflammatory response.

The role of polymorphisms in genes that regulate neurohumoral systems in patients with atrial fibrillation

One of the important medical and social present-day problems is atrial fibrillation (AF) which prevalence in the adult population is 2 % for persons under 65 and 9 % for those over 65 years of age and it is a common cause of ischemic stroke. The embolic complications incidence is 2.1 % per year in patients with paroxysmal AF, and 3.0 % per year in patients with persistent AF. The aim of the study is to analyze the modern literary sources related to the role of gene polymorphisms regulating some neurohumoral systems in group of patients with atrial fibrillation. A combination of certain genes polymorphisms can contribute to AF risk. Especially important are gene studies of the renin-angiotensin-aldosterone system (RAAS) role in the pathogenesis of AF which are currently being studied with a particular intensity. Recent data show that activation of RAAS plays an important role in the development and recurrence of AF. These studies are of great practical interest as the associative effect of angiotensin converting enzyme (ACE) inhibitors in the prevention of AF has been identified. AGT gene encodes a plasma protein known as angiotensinogen. This protein is expressed in the liver and is cleaved by the enzymatic renin action in response to lower blood pressure. The resulting product, angiotensin I, is then cleaved by ACE to the physiologically active enzyme angiotensin II. Defects in this gene may also be associated with non-hereditary AF. More than 16 spot mutations in the AGT gene were discovered, most of which resulted in amino acid substitutions. Conclusions. The analysis of the literature allows to conclude that, first, genetic polymorphisms may influence both the severity of pathological changes in the body and the efficacy of pharmacotherapy, and second, the study of RAAS gene polymorphisms may allow early detection of persons with increased risk of persistent AF recurrence and its prevention.

Angiotensin converting enzyme inhibitors or angiotensin receptors blockers equally enhances skeletal structure via different metabolic influence

The impact of renin‐angiotensin system (RAS) on bone remodeling and metabolism has gained more interest in recent years, where several RAS metabolites are deemed as potential targets for skeletal diseases. This study compares the effects of angiotensin converting enzyme (ACE) inhibitors and angiotensin‐II (AngII) type‐1 receptor (AT1R) blockers on bone structure and remodeling and investigates the involvement of neutral endopeptidase enzyme (NEP) and angiotensin 1‐9 (Ang1‐9) in ovariectomized (OVX) rats. OVX animals received either captopril or losartan for 6 weeks. Both antihypertensive agents equally attenuated the elevated levels of bone metabolic bio‐markers and restored Ca2+ and phosphorous renal elimination and bone deposition. The altered bone cortical and trabecular morphometry in OVX rats was similarly ameliorated. In femurs heads, the expressions of NEP and Ang1‐9 were enhanced by captopril, while remained unchanged in losartan groups. In addition, both drugs down‐regulated the osteoclastogenesis inducing factor, receptor activator NF‐κB ligand (RANKL), while enhanced osteoprotegerin. Although, both antihypertensive agents had different influence on local skeletal RAS metabolism, losartan and captopril equally restored bone micro‐structure in estrogen deficient animals.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Chronic Treatment With the ACE Inhibitor Enalapril Attenuates the Development of Frailty and Differentially Modifies Pro- and Anti-inflammatory Cytokines in Aging Male and Female C57BL/6 Mice.

Studies on interventions that can delay or treat frailty in humans are limited. There is evidence of beneficial effects of angiotensin converting enzyme (ACE) inhibitors on aspects related to frailty, such as physical function, even in those without cardiovascular disease. This study aimed to longitudinally investigate the effect of an ACE inhibitor on frailty in aging male and female mice. Frailty was assessed with a clinical frailty index (FI) which quantifies health-related deficits in middle-aged (9-13 months) and older (16-25 months) mice. Chronic treatment with enalapril (30 mg/kg/day in feed) attenuated frailty in middle-aged and older female mice, and older male mice, without a long-term effect on blood pressure. Enalapril treatment resulted in a reduction in the proinflammatory cytokines interleukin (IL)-1α, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1a in older female mice, and an increase in the anti-inflammatory cytokine IL-10 in older male mice compared with control animals. These sex-specific effects on inflammation may contribute to the protective effects of enalapril against frailty. This is the first study to examine the longitudinal effect of an intervention on the FI in mice, and provides preclinical evidence that enalapril may delay the onset of frailty, even when started later in life.

Angiotensin converting enzyme 1 in the median preoptic nucleus contributes to chronic intermittent hypoxia hypertension.

Obstructive sleep apnea is associated with hypertension and cardiovascular disease. Chronic intermittent hypoxia is used to model the arterial hypoxemia seen in sleep apnea patients and is associated with increased sympathetic nerve activity and a sustained diurnal increase in blood pressure. The renin angiotensin system has been associated with hypertension seen in chronic intermittent hypoxia. Angiotensin converting enzyme 1, which cleaves angiotensin I to the active counterpart angiotensin II, is present within the central nervous system and has been shown to be regulated by AP‐1 transcription factors, such as ΔFosB. Our previous study suggested that this transcriptional regulation in the median preoptic nucleus contributes to the sustained blood pressure seen following chronic intermittent hypoxia. Viral mediated delivery of a short hairpin RNA against angiotensin converting enzyme 1 in the median preoptic nucleus was used along with radio‐telemetry measurements of blood pressure to test this hypothesis. FosB immunohistochemistry was utilized in order to assess the effects of angiotensin converting enzyme 1 knockdown on the activity of nuclei downstream from median preoptic nucleus. Angiotensin converting enzyme 1 knockdown within median preoptic nucleus significantly attenuated the sustained hypertension seen in chronic intermittent hypoxia. Angiotensin converting enzyme 1 seems to be partly responsible for regulating downstream regions involved in sympathetic and blood pressure control, such as the paraventricular nucleus and the rostral ventrolateral medulla. The data suggest that angiotensin converting enzyme 1 within median preoptic nucleus plays a critical role in the sustained hypertension seen in chronic intermittent hypoxia.

Interaction between Antihypertensive Therapy Class and Pulse Pressure on Outcomes Following Acute Ischemic Stroke

Goal: The effect of pulse pressure and interactions with type of antihypertensive therapy on mortality after acute ischemic stroke has not been previously evaluated. Materials and Methods: A retrospective cohort study was conducted to evaluate the independent and interactive effects of pulse pressure and antihypertensive class (specifically angiotensin converting enzyme inhibitor/angiotensin type 1 receptor blocker, or beta blocker) on mortality following acute ischemic stroke. Findings/Conclusions: 343 patients were identified with 49 months of follow-up. Baseline pulse pressure was 64 mmHg and age was 66.5 years. Patients were divided at a pulse pressure of 70. Patients with pulse pressure ≥ 70 were older (p < 0.001) and had higher comorbid vascular burden (p = 0.031) than those with pulse pressure < 70. Pulse pressure did not remain a significant predictor of follow-up mortality after adjustment for baseline comorbidities. Angiotensin converting enzyme inhibitor/angiotensin type 1 receptor blocker based therapy was associated with lower follow-up mortality when beta blocker was not used in pulse pressure < 70 group (odds ratio 0.07, 95% confidence interval 0.01 - 0.48). Prospective analysis will be needed to confirm the protective effect of angiotensin converting enzyme inhibitor/angiotensin type 1 receptor blocker based on pulse pressure in acute ischemic stroke.

Angiotensin-converting enzyme insertion/deletion polymorphism association with obesity and some related disorders in Egyptian females: a case-control observational study.

BackgroundAccording to the WHO report in 2015, obesity is the fifth leading cause of death worldwide, and the prevalence of Egyptian female obesity is 37.5 %. Since obesity is highly influenced by genetics, and adipose tissue renin-angiotensin system is over-activated in obesity, the effect of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism on obesity and related disorders was studied in several populations, because of its effect on ACE activity. Our objective was to study the association of ACE I/D polymorphism with obesity and certain related disorders, namely hypertension, insulin resistance and metabolic syndrome, in Egyptian females.MethodsEighty female volunteers were recruited, blood pressure and body measurements were recorded and a fasting blood sample was obtained for the quantitation of glucose, lipid profile, insulin, leptin and identification of ACE I/D polymorphs. Subjects were grouped based on hypertension and obesity states. Comparisons of continuous parameters were made with independent sample t-test between two groups. The frequencies of ACE genotypes and alleles, and the association between gene polymorphism and metabolic parameters were assessed using chi-square or Fisher's exact test.ResultsGenotype frequencies were in Hardy-Weinberg equilibrium for all groups. Genotype distribution did not differ significantly between controls and cases of all the studied disorders. Although DD carriers had apparently higher parameters of blood pressure, lipid profile and insulin resistance, only diastolic blood pressure was almost significant (p = 0.057). I-carriers were significantly less susceptible to hypertension than DD carriers having normal waist/hip ratio (p = 0.007, OR = 17.29, CI = 1.81–164.96) and normal conicity index (p = 0.024, OR = 7.00, CI = 1.36–35.93). In DD genotype carriers, a significant association was found between insulin resistance and high body mass index (p = 0.004, OR = 8.89, CI = 1.94–40.71), waist circumference (p = 0.003, OR = 9.63, CI = 2.14–43.36) and waist/height ratio (p = 0.034, OR = 6.86, CI = 1.25–37.61), although the variations in percentages between DD and I-carriers were not high enough to conclude an effect of ACE I/D on such an association.ConclusionsIn this sample of Egyptian females, ACE I/D polymorphism was not significantly associated with obesity nor with any of its related disorders studied. The I allele seemed protective against hypertension in subjects with normal, not high, waist/hip ratio and conicity index compared to DD genotype carriers.

Protective role of ACE2-Ang-(1-7)-Mas in myocardial fibrosis by downregulating KCa3.1 channel via ERK1/2 pathway.

The intermediate-conductance Ca2+-activated K+ (KCa3.1) channel plays a vital role in myocardial fibrosis induced by angiotensin (Ang) II. However, as the antagonists of Ang II, the effect of angiotensin-converting enzyme 2 (ACE2)-angiotensin-(1-7)-Mas axis on KCa3.1 channel during myocardial fibrosis remains unknown. This study was designed to explore the function of KCa3.1 channel in the cardioprotective role of ACE2-Ang-(1-7)-Mas. Wild-type (WT) mice, hACE2 transgenic mice (Tg), and ACE2 deficiency mice (ACE2-/-) were administrated with Ang II by osmotic mini-pumps. As the activator of ACE2, diminazene aceturate (DIZE) inhibited increase of blood pressure, collagen deposition, and KCa3.1 protein expression in myocardium of WT mice induced by Ang II. In Tg and ACE2-/- mice, besides the elevation of blood pressure, Ang II induced transformation of cardiac fibroblast into myofibroblast and resulted in augmentation of hydroxyproline concentration and collagen deposition, as well as KCa3.1 protein expression, but the changes in ACE2-/- mice were more obvious than those in Tg mice. Mas antagonist A779 reduced blood pressure, myocardium fibrosis, and myocardium KCa3.1 protein expression by Ang II in Tg mice, but activation of KCa3.1 with SKA-31 in Tg mice promoted the pro-fibrogenic effects of Ang II. Respectively, in ACE2-/- mice, TRAM-34, the KCa3.1 blocker, and Ang-(1-7) inhibited increase of blood pressure, collagen deposition, and KCa3.1 protein expression by Ang II. Moreover, DIZE and Ang-(1-7) depressed p-ERK1/2/t-ERK increases by Ang II in WT mice, and after blockage of ERK1/2 pathway with PD98059, the KCa3.1 protein expression was reduced in WT mice. In conclusion, the present study demonstrates that ACE2-Ang-(1-7)-Mas protects the myocardium from hypertension-induced injury, which is related to its inhibiting effect on KCa3.1 channels through ERK1/2 pathway. Our results reveal that KCa3.1 channel is likely to be a critical target on the ACE2-Ang-(1-7)-Mas axis for its protective role in myocardial fibrosis and changes of KCa3.1 induced by homeostasis of ACE-Ang II-AT1 axis and ACE2-Ang-(1-7)-Mas axis may be a new therapeutic target in myocardial fibrosis.

Inibidores da enzima de conversão da angiotensina ou antagonistas dos recetores da angiotensina: evidências na mortalidade e eventos cardiovasculares major em diabéticos hipertensos

Objective: Our aim was to assess the evidence for the effects of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) on mortality and major cardiovascular events in individuals with hypertension and diabetes. Data Sources: National Guideline Clearinghouse, Guidelines Finder, Canadian Medical Association Practice Guidelines, Cochrane Library, DARE, Bandolier, MEDLINE, Index of Portuguese Medical Journals and General Directorate of Health databases. Methods: The two authors independently performed a search of meta-analyzes (MA), systematic reviews (SR), randomized clinical trials (RCT) and clinical practice guidelines (CPG), published between 31/08/2009 and 31/08/2014 in Portuguese, Spanish, English and French languages. We used the MeSH terms: Diabetes Mellitus AND Hypertension AND Angiotensin-Converting Enzyme Inhibitors OR Angiotensin Receptor Antagonists. The strength of recommendation taxonomy scale was used for the allocation of levels of evidence (LE) and strength of recommendation (SR). Results: Of the 478 articles found, we included five MA and sixCPG in this report. A Cochrane MA showed that ACE inhibitors significantly decreased mortality from all causes (LE 1) and one MA concluded that this class of medications decreased the risk of myocardial infarction (LE 1). The use of ARB was shown to decrease the risk of stroke in one MA. Another MA showed no significant differences between the two classes of drugs. A recent MA found that ACE inhibitors significantly decreased all-cause mortality, cardiovascular mortality, myocardial infarction, and heart failure (LE 1). In the same MA, ARB decreased the risk of heart failure. Most guidelines recommend ACE inhibitors or ARBs as first line therapy for hypertension in diabetic patients. Conclusions: The effects of ACE inhibitors and ARB on mortality and cardiovascular events appear to be different. We found consistent evidence favoring the use of ACE inhibitors as a first option in preventing morbidity and mortality in this population (SR A).

The effect of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use on mortality in patients with chronic kidney disease: a meta-analysis of observational studies.

There has been much controversy over the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) on patients with renal dysfunction. The purpose of this study was to summarize the evidence regarding the effect of ACEIs/ARBs administration on mortality in patients with nondialysis-dependent chronic kidney disease (CKD) by using a meta-analytic approach. We searched the PubMed, Embase, and Web of Science databases for studies on the effect of ACEIs/ARBs administration on mortality in patients with nondialysis-dependent CKD published before March 2015. Summary effect estimates with 95% confidence intervals were derived using the random-effects model, no matter whether the heterogeneity between the included studies was of statistical significance or not. Subgroup analyses, sensitivity analyses, and publication bias tests were performed. Up to 25 March 2015, 10 cohort studies were included in this meta-analysis. The hazard risk of the association between ACEIs/ARBs administration and overall mortality was 0.83 (95% confidence interval 0.78-0.87) using a random-effects model with no heterogeneity (heterogeneity test I(2) = 43.8%, p = 0.067) and publication bias (Egger's test, p = 0.763). The subgroup was divided according to estimated glomerular filtration rate, duration of follow-up, Newcastle-Ottawa Scale star, and proportion of patients with common complications including heart failure, diabetes mellitus, and hypertension. Improved survival outcomes were observed in all subgroups analysis. Sensitivity analysis proved that overall estimated effect was robust. This meta-analysis suggested that the use of ACEIs/ARBs in patients with nondialysis-dependent CKD was associated with improved survival. However, randomized studies are needed to confirm these findings and further establish causal relationship. Copyright © 2016 John Wiley & Sons, Ltd.

Angiotensin-converting enzyme gene polymorphism in migraine

Background The pathophysiology of migraine is influenced by many factors. Multiple genetic and environmental factors may contribute to the etiology of migraine. The beneficial effects of angiotensin-converting enzyme (ACE) inhibitor drugs on migraine attack frequency have been shown, and hence ACE gene polymorphism was studied for its possible effect on migrainous patients. Objective We aimed to study the relationship between the ACE gene polymorphism and migraine pathophysiology. Patients and methods The ACE genotypes of 30 migraine patients (17 cases of migraine without aura and 13 cases of migraine with aura) and 30 age-matched and sex-matched normal volunteers as a control group were studied. All patients were subjected to full clinical assessment to calculate the score on the Migraine Disability Assessment Test as an indicator of the severity of migraine and its impact on the patient life. Results The frequency of DD genotype of ACE gene was significantly higher in migraine patients, including both cases of migraine with aura and those without aura compared with the control group, but no association was found between any of the genotypes of ACE gene and the degree of migraine severity or disability. Conclusion ACE gene polymorphism may confer risk for the occurrence of migraine attacks, without affecting the symptomology or the severity of migraine.

Diet-Induced Podocyte Dysfunction in Drosophila and Mammals

Diabetic nephropathy is a major cause of end-stage kidney disease. Characterized by progressive microvascular disease, most efforts have focused on injury to the glomerular endothelium. Recent work has suggested a role for the podocyte, a highly specialized component of the glomerular filtration barrier. Here, we demonstrate that the Drosophila nephrocyte, a cell analogous to the mammalian podocyte, displays defects that phenocopy aspects of diabetic nephropathy in animals fed chronic high dietary sucrose. Through functional studies, we identify an OGT-Polycomb-Knot-Sns pathway that links dietary sucrose to loss of the Nephrin ortholog Sns. Reducing OGT through genetic or drug means is sufficient to rescue loss of Sns, leading to overall extension of lifespan. We demonstrate upregulation of the Knot ortholog EBF2 in glomeruli of human diabetic nephropathy patients and a mouse ob/ob diabetes model. Furthermore, we demonstrate rescue of Nephrin expression and cell viability in ebf2(-/-) primary podocytes cultured in high glucose.

The effect of angiotensin-converting enzyme inhibition on inflammatory and angiogenic factors in hypercholesterolemia

Renin-angiotensin system (RAS) can be activated during hyperlipidemia. Angiotensin II increases the migration of monocytes, cytokine levels, and gene expressions of VEGF and VCAM-1. With this in mind, the present work attempted to investigate the effect of angiotensin-converting enzyme (ACE) inhibition on VEGF, VCAM-1, and nitric oxide (NO) serum levels in hypercholesterolemic rats. Forty male Wistar rats were divided into 4 groups including normal diet+saline injection (control), hypercholesterol diet+saline injection, normal diet+captopril injection, and hypercholesterol diet+captopril injection. Before and after the beginning of the diet and after the treatment, the serum levels of cholesterol, triglycerides, LDL, HDL, and NO were measured. Finally, gene expressions of VCAM-1 and VEGF in the vascular cells from aorta were determined. Hypercholesterolemic diet increased the serum levels of cholesterol, LDL (p<0.001), triglycerides (p<0.01) and decreased HDL (p<0.001). Captopril caused a reduction in the serum levels of cholesterol, LDL (p<0.001), and triglycerides (p<0.05) as well as an increase in HDL levels (p<0.01). Although the serum levels of NO decreased after hypercholesterolemic diet (p<0.001), no significant change was observed after the treatment. Increased gene expressions of VEGF (p<0.05) and VCAM-1 (p<0.01) in hypercholesterolemia were regressed in captopril treated rats (p<0.01 and p<0.05, respectively). Captopril, an ACE inhibitor, improves hyperlipidemia and prevents from overexpression of genes for VEGF and VCAM-1, that are implicated in the inflammation and angiogenesis.

The Metabolic Effects of Mineralocorticoid Receptor Antagonists in Heart Failure Patients

Heart failure (HF) remains a leading cause of cardiovascular morbidity and mortality worldwide. Mineralocorticod receptor (MR) antagonists (spironolactone and eplerenone) have been studied in HF patients and in patients with acute coronary syndrome or post-myocardial infarction and left ventricular (LV) dysfunction, as well as hypertensive subjects without HF symptoms. It has suggested that mineralocorticoid receptor antagonists provide cardiovascular protection beyond its diuretic and potassium-sparing capacities. Traditionally, progression of HF relates with not full blockade of renin-angiotensin system (RAS) activation and with so called “escape” phenomenon of neurohumoral activation from effects of angiotensin converting enzyme / angiotensin receptor blockers and beta-adrenoblockers. Circulating and local aldosteron over production is discussed a main cause of none adequate effect of RAS blockade contributed negative cardiovascular remodelling and worse survival. During the last decade, several studies have shown that completed control for RAS activation might be achieved through adding MR antagonists in contemporary treatment scheme. This approach raises survival and leads to a trend in declined mortality rate in patients with HF various etiologic causes. Therefore, there are increasing evidence that both MR antagonists spironolactone and eplerenone might have a different metabolic effect in HF patients and that this difference is required to pay attention in creating of optimal HF therapeutic program. The aim of the mini review is to evaluate clinically significance of metabolic effects of mineralocorticoid receptor antagonists in HF patients.

Effects of ACEI/ARB in hypertensive patients with type 2 diabetes mellitus: a meta-analysis of randomized controlled studies

BackgroundThe effects of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) on cardiovascular (CV) risk in hypertensive patients with type 2 diabetes mellitus (T2 DM) are uncertain. Our objective was to analyze the effects of ACE/ARBs, on the incidence of myocardial infarction, stroke, CV events, and all-cause mortality in hypertensive patients with T2 DM.MethodPubMed and Embase databases were searched through January 2014 to identify studies meeting a priori inclusion criteria and references in the published articles were also reviewed. Two investigators independently extracted the information with either fixed-effect model or random-effect model to assess the effects of ACE/ARBs treatment in hypertensive patients with T2 DM.ResultsTen randomized controlled studies were included with a total of 21,871 participants. Overall, treatment with ACE/ARBs in hypertensive patients with T2 DM was associated with a statistically significant 10% reduction in CV events, pooled hazard ratio (HR) of 0.90 [95% confidence intervals (CI): 0.82-0.98] with no heterogeneity (I2 = 19.50%; P = 0.275);and 17% reduction in CV mortality, pooled HR of 0.83 [95% CI: 0.72-0.96] with no heterogeneity (I2 = 0.9%; P = 0.388). ACE/ARBs was not associated with MI, stroke and all-cause mortality.ConclusionsTreatment with ACE/ARBs results in significant reduction in CV events and mortality in hypertensive patients with T2 DM.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2261-14-148) contains supplementary material, which is available to authorized users.

Ramipril Lowers Plasma FGF-23 in Patients with Diabetic Nephropathy

Background/Aims: Ramipril attenuates renal Fibroblast growth factor-23 (FGF-23) expression, ameliorates proteinuria and normalizes serum phosphate in the diabetic Zucker rat with progressive renal disease suggesting that the renoprotective effect by this drug may be in part due to a FGF-23-lowering effect of angiotensin-converting enzyme (ACE) inhibition. Methods: In this nonrandomized study, we tested whether ACE-inhibition reduces circulating FGF-23 in type-2 diabetics with stage-1 chronic kidney disease (CKD) and proteinuria. Intact FGF-23, the eGFR, proteinuria and the endothelium-dependent flow-mediated (FMD) response to ischemia and other parameters were measured at baseline and after 12-weeks of treatment with ramipril (n = 68) or amlodipine (n = 32). Results: Blood Pressure (BP) fell to a similar extent (p < 0.001) in the two groups. However, 24 h proteinuria and the FMD improved more (both p < 0.01) in ramipril-treated patients than in amlodipine-treated patients. Changes in proteinuria (r = 0.47) and in FMD (r = -0.49) by ramipril were closely associated (p < 0.001) with simultaneous changes in FGF-23 and this link was confirmed in multiple regression analyses. In these analyses, the relationship between FMD and proteinuria changes attained statistical significance (p < 0.01) only in a model excluding FGF-23 suggesting that endothelial dysfunction and FGF-23 share a common pathway conducive to renal damage. Conclusion: Findings in this study contribute to generate the hypothesis that FGF-23 may be implicated in proteinuria and in endothelial dysfunction in diabetic nephropathy (clinicaltrials.gov (NCT01738945)).

Lack of Efficacy of Drug Therapy in Preventing Takotsubo Cardiomyopathy Recurrence: A Meta‐analysis

Efficacy of chronic drug therapy in prevention of stress-induced cardiomyopathy recurrences is not well established. We therefore aimed to evaluate in this meta-analysis whether pharmacological treatment can effectively prevent takotsubo cardiomyopathy (TTC) recurrences, according to available studies. There is no evidence for preventing TTC recurrence by drug therapy. After a PubMed search, we conducted a meta-analysis of available studies (clinical nonrandomized registries) on efficacy of drug therapy in preventing recurrence of TTC. A total of 23 (4.5%) TTC recurrences occurred in the 511 patients included in the analysis. Seven studies on the effects of β-blockers on prevention of TTC recurrence were evaluated; the odds ratio (OR) was 0.44 and the 95% confidence interval (CI) was 0.15-1.31. In 5 studies on the effects of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, the OR was 0.42 and the 95% CI was 0.08-2.36; in 3 studies on statins, the OR was 0.74 and the 95% CI was 0.07-7.3; and in 4 studies on aspirin, the OR was 0.33 with a 95% CI of 0.05-2.17 (P value not significant in all cases). A meta-analysis of the efficacy of different medications through the clinical TTC registries available showed no clinical evidence for a standard drug treatment in the chronic management of TTC. β-Blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, statins, and aspirin do not seem to significantly reduce recurrences of TTC. Randomized, adequately powered studies are needed to further assess this issue.

Direct regulation of ENaC by bradykinin in the distal nephron. Implications for renal sodium handling

Locally produced peptide hormones kinins, such as bradykinin, are thought to oppose many of the prohypertensive actions of the renin-angiotensin-aldosterone system. In the kidney, bradykinin, via stimulation of B2 receptors (B2R), favors natriuresis mostly due to the inhibition of tubular Na reabsorption. Recent experimental evidence identifies the epithelial Na channel (ENaC) as a key end effector of bradykinin actions in the distal tubular segments. The focus of this review is the physiological relevance and molecular details of the bradykinin signal to ENaC. The recent epidemiological GenSalt study demonstrated that genetic variants of the gene encoding B2R show significant associations with the salt sensitivity of blood pressure. Bradykinin was shown to have an inhibitory effect on the distal nephron sodium transport via stimulation of B2 receptor-phospholipase C (B2R-PLC) cascade to decrease ENaC open probability. Genetic ablation of bradykinin receptors in mice led to an augmented ENaC function, particularly during elevated sodium intake, likely contributing to the salt-sensitive hypertensive phenotype. Furthermore, augmentation of bradykinin signaling in the distal nephron was demonstrated to be an important component of the natriuretic and antihypertensive effects of angiotensin converting enzyme inhibition. Salt-sensitive inhibition of ENaC activity by bradykinin greatly advances our understanding of the molecular mechanisms that are responsible for shutting down distal tubule sodium reabsorption during volume expanded conditions to avoid salt-sensitive hypertension.