Angiotensin-converting Enzyme Inhibitor Group Research Articles

The Role of Angiotensin-Converting Enzyme Inhibitors in Patients with Chronic Subdural Hematoma: A Scandinavian Population-Based Multicenter Study.

To investigate the role of angiotensin converting enzyme (ACE) inhibitors in the recurrence of chronic subdural hematoma (cSDH) after burr hole surgery. A retrospective review was conducted of a Scandinavian multicenter, population-based cohort of 1252 adults with cSDH who underwent with burr hole surgery between January 1, 2005, and December 31, 2010. The risk of cSDH recurrence was assessed in users of ACE inhibitors, users of angiotensin II receptor blockers (ARBs), and those without ACE inhibitor treatment (no ACE inhibitor group) using univariable and multivariable regression analyses. The cohort included 98 (7.8%) ACE inhibitor users and 63 (5%) ARB-only users. The recurrence rate was 16.3% (n= 16) in the ACE inhibitor group, compared with 13.3% (n= 153) in the no ACE inhibitor group (P= 0.39) and 14.3% (n= 9) in the ARB group (P= 0.73). When comparing groups, age (P= 0.01), Charlson Comorbidity Index (P= 0.01), use of platelet inhibitors (P= 0.001) and use of anticoagulants (P= 0.01) differed between the ACE inhibitor and no ACE inhibitor groups. Only age differed significantly between the ACE inhibitor and ARB groups (P= 0.03). In the analyses adjusted for differences in baseline characteristics, ACE inhibitor treatment did not influence the risk of recurrence (odds ratio, 1.2; 95% confidence interval, 0.7-2.2; P= 0.46). In this population-based study, the use of ACE inhibitors was not associated with the risk of recurrence following burr hole surgery for cSDH.

Early initiation of angiotensin-converting enzyme inhibitors in postrenal transplant period: A study from a state-run tertiary care center

Angiotensin-converting enzyme inhibitors (ACEi) comprise a drug class, which are potent antihypertensives with renoprotective effects but are grossly underutilized in renal transplant recipients. These drugs have been reported to cause elevated potassium and creatinine levels in some renal transplant patients. There have been no reports of prospective studies on use of ACEi in renal transplant patients in the early post-transplant period. The purpose of this study is to assess the safety of an ACEi, when started in the early post-transplant period. In this prospective observational study, we reviewed 78 kidney transplant recipients during the period of January 2012 to March 2017 at our institution. Sixty-four patients were initiated on ACEi therapy within a month of transplantation, while 14 were initiated after one-month post-transplant; the latter was classified as late initiation group. Patients were enrolled when they met the following criteria: declining serum creatinine, improving urine output, and serum potassium <5.5 mEq/L. Exclusion criteria included anaphylaxis to ACEi, use of ACEi or angiotensin receptor blocker for the treatment of post-transplant erythrocytosis, and serum potassium >5.5 mEq/L. Sixty-four patients were studied, 53 (83%) were male and 11 (17%) were female. Mean age was 32 ± 15 years (12-56). Minimum duration of follow-up was six months. For each patient, hemoglobin, serum creatinine, and potassium levels were tested at the beginning of ACEi and at the end of the first, third, and the sixth month. The average potassium and hemoglobin levels did not differ significantly between the groups and were within the normal clinical ranges. While incidence of graft failure did not differ, death with functioning graft was lower in the ACEi group. ACEi can successfully be used in postrenal transplant with beneficial long-term impact on renal function. However, here is a need for further randomized controlled studies to validate this observation.

Effects of Angiotensin-Converting Enzyme Inhibition on Circulating Endothelial Progenitor Cells in Patients with Acute Ischemic Stroke.

Background Therapeutic neovascularization might represent an important strategy to salvage tissue after ischemia. Circulating bone marrow-derived endothelial progenitor cells (EPCs) were previously shown to augment the neovascularization of ischemic tissue. Angiotensin-converting enzyme inhibitors (ACEIs) might modulate EPC mobilization. We evaluated populations of circulating stem cells and early EPCs in acute ischemic stroke (AIS) patients and the effect of ACEI on circulating EPCs in these patients with respect to aspects of stroke pathogenesis. Methods We studied 43 AIS patients (group I), comprising 33 treated with ACEI (group Ia) and 10 untreated (group Ib). Risk factor controls (group II) included 22 subjects. EPCs were measured by flow cytometry. Results In AIS patients, the number of circulating stem cells and early EPCs upon admission was similar to that in control group individuals. There were no significant differences in the numbers of stem cells and early EPCs over subsequent days after AIS. There were also no significant differences in stem cell and early EPC numbers over the first 3 days between group Ia and group Ib. However, on day 7, these numbers were significantly higher in group Ib than in group Ia (p < 0.05). In AIS patients chronically treated with ACEI, there was a negative correlation between CD133+ cell number and neurological deficit on the first, third, and seventh days (p < 0.005). Conclusions An increased number of circulating stem cells and early EPCs were not observed in stroke patients chronically treated with ACEI. In patients chronically treated with ACEI, a significant correlation was observed between decreased neurological deficit and higher levels of CD133+ cells; this could be due to the positive influence of these cells on the regeneration of the endothelium and improved circulation in the ischemic penumbra.

Gambaran Pengetahuan Pasien Hipertensi Terhadap Penyakit Hipertensi Dan Obat Antihipertensi Golongan Ace-Inhibitor Dan Diuretik

Hypertension is a circumstances where patient having enhancement blood pressure above the normal rate was 120/80 mm/Hg. Hypertension is a disease can’t cured and can make many complication. One of pharmacology treatment can do for decrease blood pressure and prevent complication is using drug ACE-Inhibitor and diuretic group. The purpose of this research to know an overview of knowledge hypertension patient about the disease and drug ACE-Inhibitor and diuretic group.This is descriptif research using survey method, was done in Februari 2015 at UPTD Puskesmas Melur Pekanbaru with the number of respondent as much 81 patient consist of 50 respondent for ACE-Inhibitor group drug and 31 respondent for diuretic drug. Generally an overview of knowledge hypertension patient toward to hypertension disease was enough as much 38 patient (47%) and toward to ACE-Inhibitor group was less as much 30 respondent (60%) and to diuretic drug was enough as much 16 patient (52%).&#x0D; &#x0D; Keyword : Knowledge, Hypertension, ACE-Inhibitor drug an diuretic drug

Olmesartan is not associated with the risk of enteropathy: a Korean nationwide observational cohort study.

Background/AimsOlmesartan, a widely used angiotensin II receptor blocker (ARB), has been linked to sprue-like enteropathy. No cases of olmesartan-associated enteropathy have been reported in Northeast Asia. We investigated the associations between olmesartan and other ARBs and the incidence of enteropathy in Korea.MethodsOur retrospective cohort study used data from the Korean National Health Insurance Service to identify 108,559 patients (58,186 females) who were initiated on angiotensin converting enzyme inhibitors (ACEis), olmesartan, or other ARBs between January 2005 and December 2012. The incidences of enteropathy were compared among drug groups. Changes in body weight were compared after propensity score matching of patients in the ACEis and olmesartan groups.ResultsAmong 108,559 patients, 31 patients were diagnosed with enteropathy. The incidences were 0.73, 0.24, and 0.37 per 1,000 persons, in the ACEis, olmesartan, and other ARBs groups, respectively. Adjusted rate ratios for enteropathy were: olmesartan, 0.33 (95% confidential interval [CI], 0.10 to 1.09; p = 0.070) and other ARBs, 0.34 (95% CI, 0.14 to 0.83; p = 0.017) compared to the ACEis group after adjustment for age, sex, income level, and various comorbidities. The post hoc analysis with matched cohorts revealed that the proportion of patients with significant weight loss did not differ between the ACEis and olmesartan groups.ConclusionsOlmesartan was not associated with intestinal malabsorption or significant body weight loss in the general Korean population. Additional large-scale prospective studies of the relationship between olmesartan and the incidence of enteropathy in the Asian population are needed.

Early treatment with zofenopril and ramipril in combination with acetylsalicylic acid after acute myocardial infarction: long-term benefits of zofenopril

Co-administration of Angiotensin-converting enzyme inhibitors (ACEIs) and acetylsalicylic acid in patients with acute myocardial infarction can improve the prognosis of the disease and reduce the likelihood of cardiovascular events occurring over a long period of time. The use of zofenopril is of particular interest, since in most clinical studies it has shown maximum efficacy and greater influence on the further course of coronary heart disease, as compared with other representatives of the ACE inhibitor group. One of these studies was SMILE-4 (Comparison between zofenopril and ramipril in combination with acetylsalicylic acid in patients with left ventricular systolic dysfunction after acute myocardial infarction: results of a randomized, double-blind, parallelgroup, multicenter, European study). Patients who participated in this study were subject to further follow-up for 9 years. At the end of the observation period, it was found that zofenopril, in comparison with ramipril, in combination with acetylsalicylic acid, contributes to better survival of patients and a reduction in the risk of hospitalization for cardiovascular events.

STRESS DEGRADATION OF LISINOPRIL DIHYDRATE IN DIFFERENT AQUEOUS MEDIA

Lisinopril is an antihypertensive drug from the ACE inhibitor group. It is often used in practice and, in oral administration is characterized by very low percentage of resorption (~25%). Therefore, it is important to ensure the stability of this drug, since any degradation leads to a decrease in the percentage of resorption and an increased risk of sub-dosage of patients. In accordance with modern trends of pharmaceutical analysis, the chemical stability of lisinopril under the influence of various aqueous media was tested: distilled water, 0.1M HCl, 0.1M and 0.01M NaOH and 3% hydrogen peroxide solution. In order to clearly define the effect of elevated temperature on the stability of this drug, tests were carried out at 25 °C and 50 °C. High-pressure liquid chromatography was used as the method for stability testing. The obtained results clearly define that lisinopril is the most sensitive to hydrolysis in the base environment, where at 25 °C, in the first minute, it degrades ~100%. In this paper, kinetic parameters (degradation constant rate, half-life of degradation, order kinetics, and activation energy) were also determined, which enabled clear definition of the stability and identification of degradation products of lisinopril under the influence of various stress agents. In the degradation of lisinopril in neutral and acidic medium, impurity D is identified as the main degradation product.

Orthostatic Hypotension and Therapy with an Ace Inhibitor in Hypertensive Patients

Abstract Orthostatic hypotension (OH) is defined as a drop in the systolic blood pressure greater than 20 mmHg and that of the diastolic blood pressure greater than 10 mmHg within 3 minutes from the change of the body’s position from lying or sitting down to standing up. The objective of this study is to analyse the incidence and severity of orthostatic hypertension when taking one of the generic representatives of the ACE inhibitor group (trandolapril) as a monotherapy in patients with essential hypertension. Th e study involved 314 patients (medium age of 54±4 years; 52.5% men) with poorly regulated hypertension for whom trandolapril was introduced as monotherapy. Th e incidence rates of patients with and without orthostatic hypotension between the first and second examination were not statistically significantly different. At the second control examination, 7 patients (2,3%) still had orthostatic hypotension, as was the case at the first examination. Between the third and fourth controls, a statistically significant decrease in the number of patients with orthostatic hypotension was recorded. No statistically significant difference in the incidence of orthostatic hypotension between patients with normal body mass and those who were overweight was observed. Our study has shown that certain ACE inhibitors, such as Trandolapril, do not have a pronounced adverse effect with regard to orthostatic hypotension and that in long-term application, they can have a positive role in the prevention of hypotensive episodes and improving patient compliance.

Angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers in acute ST-segment elevation myocardial infarction patients with diabetes mellitus undergoing percutaneous coronary intervention

BackgroundDiabetes Mellitus (DM) is an important factor of adverse cardiovascular events in acute ST-segment elevation myocardial infarction (STEMI) patients. Renin-angiotensin-aldosterone system (RAAS) inhibitors is associated with improved clinical outcomes, however, there are limited data comparing the effectiveness of two different RAAS inhibitors in STEMI patients with DM undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES). MethodsA total of 3811 eligible STEMI patients with DM were enrolled in Korea Acute Myocardial Infarction Registry (KAMIR). They were stratified into two groups: Angiotensin converting enzyme inhibitors (ACEI) group (n=2691) and angiotensin receptor blockers (ARB) group (n=1120). To adjust baseline confounding factors, we performed propensity score matching (PSM) analysis and evaluated individual and composite major clinical outcomes between the two groups up to 2years. ResultsAfter PSM, a total of 1049 well-matched pairs were generated. Baseline clinical, angiographic and procedural characteristics were well-balanced between the two groups. The incidence of death, recurrent myocardial infarction (MI), revascularization and major adverse cardiac events (MACE) were not significantly different between the two groups up to 2years, ConclusionIn the present study, ACEI and ARB showed comparable effectiveness and safety on individual and composite clinical outcomes in STEMI patients with DM who underwent successful PCI with DES at least up to 2years.

A prospective study of various anti hypertensive drugs on reversal of left ventricular hypertrophy in hypertensive Bangladeshi population

Regression of ventricular hypertrophy is the restoration of normal ventricular structure and physiology after the hypertrophy has developed. It has been clearly demonstrated that once left ventricular hypertrophy (LVH) is diagnosed, it represents a strong blood pressure independent risk factor for cardiovascular morbidity and mortality.This prospective observational study was carried out in Department of Cardiology, BSMMU, Dhaka to compare the effectiveness of different anti-hypertensive agents in reducing left ventricular hypertrophy (LVH) in hypertensive Bangladeshi population involving 95 patients with clinically diagnosed hypertension. The duration of study was from July 2005 to Tune 2008. Out of these 95 patients, 20 were included in beta-blocker(BB) group, 14 in angiotensin converting enzyme inhibitor(ACEi) group, 20 in beta-blocker(BB) + diuretic(DD) group, 14 in angiotensin converting enzyme inhibitor(ACEi) + diuretics(DD) group, 13 in beta-blocker(BB) and angiotensin enzyme inhibitor(ACEi) group and 14 in beta-blocker(BB) + angiotensin converting enzyme inhibitor(ACEi) + diuretic(DD) group. patients were followed-up at 8 weeks, 6 months, 1 year and at 2 years. A baseline M-mode echocardiography was done to document LVH. Among three groups of anti-hypertensive drugs, angiotensin converting enzyme inhibitor alone has been found to be most effective as compared to beta blockers when used alone than in combination groups (Beta blocker plus ACEi plus Diuretics or Beta blocker plus ACEi). Although, statistically not significant, a clear benefit has been shown in all groups in terms of LVH regression.Bangladesh Med J. 2016 Sep; 45 (3): 156-159

Hydrogen sulfide - an important signaling molecule in the pathogenesis of cardiovascular diseases: the possibility of therapeutic intervention

Diseases of the cardiovascular system have several signal molecules, among which the most important are hydrogen sulphide and nitric oxide. The role of hydrogen sulfide has long been ignored, but today it is known that the level of this substance varies during the course of pathological processes in the heart or blood vessels. Therefore, for treatment use drugs that affect the synthesis and bioavailability of hydrogen sulphide in the body. In the group of ACE inhibitors such a drug is zofenopril (Zokardis®), which in its composition has two sulfhydryl groups. This feature provides vasodilator, cardioprotective, antioxidant and anti-ischemic effects. The use of zofenopril is pathogenetically shown in hypertensive disease, especially when combined with coronary heart disease.

STRESS DEGRADATION OF LISINOPRIL DIHYDRATE IN DIFFERENT AQUEOUS MEDIA

Lisinopril is an antihypertensive drug from the ACE inhibitor group. It is often used in practice and, in oral administration is characterized by very low percentage of resorption (~25%). Therefore, it is important to ensure the stability of this drug, since any degradation leads to a decrease in the percentage of resorption and an increased risk of sub-dosage of patients. In accordance with modern trends of pharmaceutical analysis, the chemical stability of lisinopril under the influence of various aqueous media was tested: distilled water, 0.1M HCl, 0.1M and 0.01M NaOH and 3% hydrogen peroxide solution. In order to clearly define the effect of elevated temperature on the stability of this drug, tests were carried out at 25 °C and 50 °C. High-pressure liquid chromatography was used as the method for stability testing. The obtained results clearly define that lisinopril is the most sensitive to hydrolysis in the base environment, where at 25 °C, in the first minute, it degrades ~100%. In this paper, kinetic parameters (degradation constant rate, half-life of degradation, order kinetics, and activation energy) were also determined, which enabled clear definition of the stability and identification of degradation products of lisinopril under the influence of various stress agents. In the degradation of lisinopril in neutral and acidic medium, impurity D is identified as the main degradation product.

Effect of apoptosis signal regulating kinase 1 inhibitor on glomerulosclerosis in 5/6 nephrectomy rats

Objective To assess whether combined apoptosis signal regulating kinase 1 inhibitor (ASK-1I) with angiotensin-converting-enzyme inhibitor (ACEI) could achieve enhanced benefits compared to monotherapy on 5/6 nephrectomy rats. Methods Adult male Sprague Dawley rats underwent 5/6 nephrectomy (5/6 Nx) at week 0 and renal biopsy at week 8. Rats were randomized to four groups with equal glomerulosclerosis: control group, ASK-1 inhibitor group, ACEI group and combination group. After treatment for 4 weeks, animals were sacrificed at week 12. Systolic blood pressure (SBP), albumin to creatinine ratio (ACR), serum creatinine and creatinine clearance rate (Ccr) were measured at intervals. At week 8 and 12, the degree of glomerulosclerosis was evaluated. Results All rats developed hypertension, proteinuria and glomerulosclerosis from week 0 to 8. At 12th week, blood pressure (BP) in ACEI group was significantly lower than in control group (P<0.05). ACR growth rate in ACEI group and combination group was significantly lower than in control group [(57.8±24.4)%, (50.2±27.5)%, (244.9±69.4)% respectively, P<0.05]. Creatinine growth rate in ASK-1 inhibitor group and combination group was lower than in control group [(19.1±17.5)%, (22.3±17.7)%, (89.8±24.7)% respectively, P<0.05]. Simultaneously, the glomerulosclerosis could be effectively reversed in combination group (P<0.05). Conclusion Combined use of ASK-1I with ACEI can reduce BP, proteinuria and glomerulosclerosis significantly, and can improve renal function. Key words: Apoptosis signal regulating kinase 1 inhibitor; Angiotensin-converting-enzyme inhibitor; Albumin to creatinine ratio; Creatinine clearance rate; Glomerulosclerosis

Combined use of renin-angiotensin-aldosterone system-acting agents: a cross-sectional study.

Background Due to recent EU warnings and restrictions on the combined use of renin-angiotensin-aldosterone system (RAAS)-acting agents, and the seriousness of the associated harm, we analyzed the prescription of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) as dual therapy or associated with spironolactone. Setting An administrative claims database of a regional hospital in Romania. Methods We retrospectively included all adult patients hospitalized during 18months in 2013-2014, discharged with a prescription of a RAAS-acting agent. Main outcome measures Counts of ACEIs and ARBs co-prescription, of ACEIs or ARBs combined with spironolactone, co-morbidities, co-medication, creatinine, and electrolytes assessment and values. Results Out of 1697 patients with a prescription of a RAAS-acting agent, 24 (1.4%) were co-prescribed ACEIs and ARBs, and 416 (24.5%) ACEIs or ARBs with spironolactone. Patients prescribed dual ACEI/ARB therapy and the ones with ACEI or ARB-spironolactone combination had significantly higher prevalence of increased creatinine level before discharge, compared to the ACEI and ARB monotherapy groups (48 and 31% compared to 17 and 27%). Subjects with diabetes, heart failure, ischaemic heart disease, or urea ≥40mg/dL had higher odds of having ACEI or ARB-spironolactone combination compared to monotherapy, while hypertension and renal disease subjects had lower odds. Similar findings were comparing dual ACEI/ARB therapy to monotherapy except heart failure (not statistically significant). Conclusion Overall, the prevalence of use of dual therapy was low. The combined use of RAAS-acting agents was higher in patients with known risk factors for further renal function deterioration, compared to the ones without.

Acute Bradykinin Receptor Blockade During Hemorrhagic Shock in Mice Prevents the Worsening Hypotensive Effect of Angiotensin-Converting Enzyme Inhibitor.

Angiotensin-converting enzyme inhibitors are associated with deleterious hypotension during anesthesia and shock. Because the pharmacologic effects of angiotensin-converting enzyme inhibitors are partly mediated by increased bradykinin B2 receptor activation, this study aimed to determine the impact of acute B2 receptor blockade during hemorrhagic shock in angiotensin-converting enzyme inhibitor-treated mice. In vivo study. University research unit. C57/Bl6 mice. The hemodynamic effect of B2 receptor blockade using icatibant (B2 receptor antagonist) was studied using a pressure-targeted hemorrhagic shock and a volume-targeted hemorrhagic shock. Animals were anesthetized with ketamine and xylazine (250 mg/kg and 10 mg/kg, respectively), intubated using intratracheal cannula, and ventilated (9 mL/kg, 150 min). Five groups were studied: 1) sham-operated animals, 2) control shocked mice, 3) shocked mice treated with ramipril for 7 days (angiotensin-converting enzyme inhibitors) before hemorrhagic shock, 4) shocked mice treated with angiotensin-converting enzyme inhibitors and a single bolus of icatibant (HOE-140) immediately before anesthesia (angiotensin-converting enzyme inhibitors + icatibant), and 5) shocked mice treated with a single bolus of icatibant. One hour after volume-targeted hemorrhagic shock, blood lactate was measured to evaluate organ failure. During pressure-targeted hemorrhagic shock, the mean blood volume withdrawn was significantly lower in the angiotensin-converting enzyme inhibitor group than in the other groups (p < 0.001). During volume-targeted hemorrhagic shock, icatibant prevented blood pressure lowering in the angiotensin-converting enzyme inhibitor group (p < 0.001). Blood lactate was significantly higher in the angiotensin-converting enzyme inhibitor group than in the other groups, particularly the HOE groups. During hemorrhagic shock, acute B2 receptor blockade significantly attenuates the deleterious hemodynamic effect of angiotensin-converting enzyme inhibitor treatment in mice. This beneficial effect of B2 receptor blockade is rapidly reached and sustained with a single bolus of icatibant. This benefit could be of interest in angiotensin-converting enzyme inhibitor-treated patients during both emergency anesthesia and resuscitation.

PP.01.10] TREATMENT WITH BETA-BLOCKERS REDUCES THE DIFFERENCE BETWEEN CLINICAL AND AMBULATORY BLOOD PRESSURE LEVELS IN PATIENTS WITH STABLE ARTERIAL HYPERTENSION

Objective: The aim of our study was to assess the effect of antihypertensive treatment (beta-blockers (BB), angiotensin I receptor antagonists (ARA), calcium antagonists (AC), angiotensin converting enzyme inhibitors (ACEI) on the difference between clinical and ambulatory blood pressure level.Design and method: We analyzed 292 ambulatory blood pressure monitoring (ABPM) data of AH patients without serious concomitant diseases. The difference between clinical and ambulatory blood pressure level was assessed as the difference between clinical BP measurement and mean daytime BP. The inclusion criteria were: >6-days wash-out period; two ABPM (SpaceLabs 90207) sessions before treatment and during treatment; daytime BP before treatment >140/90 and < 160/110 mmHg; 2–3 months treatment period with mean therapeutic doses. The BB group included metoprolol receiving patients (35), ARA group - losartan and telmisartan (36), ACEI group - captopril and enalapril (35), AC group - amlodipin (40). We used Spearman Partial Coefficient for correlation analysis adjusted for age, sex and duration of AH. Results: We found that all antihypertensive drugs significantly decreased systolic and diastolic BP (SBP, DBP) levels. Long-term BB therapy significantly reduced difference between systolic and diastolic clinical and ambulatory blood pressure diastolic. Antihypertensive treatment with other drugs has not significantly reduced the difference between clinical and ambulatory blood pressure (see table). Conclusions: BB decreased difference between clinical and ambulatory blood pressure. Probably BB reduced stress - induced increase of the sympathetic nervous system activity during clinic visit and therefore clinic BP level more significantly than other drugs.

The effects and mechanisms of benazepril and losartan on glomerular podocyte autophagy in aged spontaneously hypertensive rats

Objective To examine the effects of benazepril and losartan on glomerular podocyte autophagy in aged spontaneously hypertensive rats (SHRs) and investigate the underlying mechanisms of renal-protective effects of angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB). Methods Wistar-Kyoto rats (WKYs) were used as the normal control (NORM) group (2 ml physiological saline per day). SHRs were randomly divided into 4 groups: the CTRL group (2 ml physiological saline per day), the ACEI group (10 mg·kg-1·d-1), the ARB group (30 mg·kg-1·d-1) and the combined group (10 mg·kg-1·d-1 benazepril and 30 mg·kg-1·d-1), with six 18-month-old male rats in each group. The experiments were conducted during a 4-month period. Blood pressure was monitored regularly. At the end of the experiments, we measured the levels of urine protein, urine creatinine, serum creatinine (SCR), blood urea nitrogen (BUN), and serum and renal cortex angiotensin Ⅱ (AngII). Ultrastructural changes in the kidney were examined under light and transmission electron microscopy. The expressions of nephrin, LC3BII, Atg5 and p62 in the glomerulus were analyzed by Western blot analysis. Results After treatment, the blood pressure and the urine albumin/creatinine ratio of the four SHR groups were still significantly higher than those of the NORM group, but the blood pressure and the urine albumin/creatinine ratio of the ARB group and the combined group were significantly lower than those of the CTRL group (all P 0.05); The level of serum AngII of the combined group was significantly higher than that of the CTRL group 〔CTRL (0.08±0.00) μg/L, Combined (0.12±0.01) μg/L, P<0.05〕; The levels of cortex AngII of the four SHR groups were significantly lower than those of the NORM group, while the level of cortex AngII of the ARB group was significantly higher than that of the CTRL group (all P<0.05); Renal ultrastructural examination revealed shrunken glomeruli, fused or effaced epithelial cell foot processes, and focal atrophy of renal tubules in the four SHR groups. These pathological changes were more serious in the CTRL group but less so in the combined group. There were significantly more autophagosomes in the NORM group and the combined group than in the CTRL group (P<0.05). Compared with the NORM group, the expressions of nephrin, LC3BII, Atg5 and p62 in the CTRL group were suppressed significantly (P<0.05). The expressions of nephrin, LC3BII and Atg5 in the ACEI group and the expressions of nephrin, LC3BII, Atg5 and p62 in the ARB group and the combined group were higher than in the CTRL group (P<0.05). Conclusions ACEI/ARB can decrease the autophagic activity of glomerular podocytes. The renal-protective effects of ACEI/ARB may be mediated by glomerular podocyte autophagy, which is induced by AngII. Key words: Hypertension; Podocytes; Autophagy; Angiotensin-converting enzyme inhibitor; Angiotensin receptor antagonist

Effects of cardiovascular drugs on TSH serum levels in patients on replacement therapy after thyroidectomy

Hypothyroidism is one of most common endocrine disorders resulting from deficiency of thyroid hormones. The aim of our study was to investigate whether cardiovascular drugs as well as gender, age, body-mass index, and habits, like smoking or drinking coffee affect thyroid-stimulating hormone (TSH) level in hypothyroid patients with thyroxine replacement therapy who suffer from cardiovascular disease. The study was conducted on 150 hypothyroid patients who underwent total thyroidectomy for benign reasons; they were divided into five treatment groups: levothyroxine only group and, according to the drugs they had in therapy alongside levothyroxine, the angiotensinconverting enzyme inhibitors group, the selective β-blockers group, the calcium antagonists group, as well as the nitrates group. A retrospective cohort study was conducted in the Clinical Center Kragujevac, Serbia, during the period of January 2012 to October 2014. All patients' data were collected both from participants' health records and questionnaires that patients completed, including data about habits, like smoking or drinking coffee. TSH values were significantly higher in the group of patients with selective β-blockers in therapy alongside levothyroxine, compared to all the other study groups. The values of TSH level did not significantly differ among the other therapy groups. On the other hand, cigarette smoking was a risk factor that decreased TSH levels in patients on thyroid replacement therapy. Our study shows that selective β-1 blockers can increase, while cigarette smoking can decrease TSH serum levels in hypothyroid patients on thyroid-replacement therapy.

Association between visual improvement after photocoagulation and the use of angiotensin converting enzyme inhibitors in diabetic macular oedema

Abstract Background Angiotensin converting enzyme inhibitors are effective in delaying the progression of diabetic retinopathy. It is unknown if their use is associated with a better visual outcome in patients with diabetic macular oedema. Material and methods A non-experimental, comparative, longitudinal and retrospective study was performed on patients with diabetic macular oedema treated by focal photocoagulation, and with systemic arterial hypertension treated with angiotensin converting enzyme inhibitors (Group 1), and without hypertension (Group 2). The dependent variable was the proportion with visual improvement, operatively defined as the gain of one or more lines of vision three weeks after photocoagulation. The independent variable was the use of angiotensin converting enzyme inhibitors. The proportion of eyes with visual improvement after treatment was compared between groups using the Chi squared ( χ 2 ) test. Results A total of 33 eyes (51.6%) were assigned to group 1, and 31 (48.2%), to group 2. The mean of visual acuity improved after three weeks, compared with baseline ( p = 0.002). The proportion of eyes with visual improvement did not differ between patients treated with angiotensin converting enzyme inhibitors (45.5%) and those that did not use them (51.6%, p = 0.4). Conclusions There was no statistical difference in the proportion of eyes with visual improvement between patients treated with angiotensin converting enzyme inhibitors and in those where they were not used. There is no support for the inhibition of angiotensin II in addition to photocoagulation for improving the outcome in patients with diabetic macular oedema.

Effect of Angiotensin-Converting Enzyme Inhibitors in Contrast-Induced Nephropathy: A Meta-Analysis

Aims: The purpose of this study was to evaluate the effect of angiotensin-converting enzyme inhibitors (ACEIs) on contrast-induced nephropathy (CIN) in patients undergoing coronary angiography or percutaneous coronary intervention (PCI). Methods: We searched the Medline, Embase, Cochrane Library, China National Knowledge Infrastructure, Chongqing VIP database and Wanfang database up to December 2014. Pooled risk ratios (RRs) or weighted mean difference (WMD) with their 95% CIs for the CIN incidence, serum creatinine (SCr), estimated glomerular filtration rate (eGFR) and blood urea nitrogen (BUN) of the patients were collected and calculated using the software Review Manager 5.2. Results: A total of 12 separate studies including 1,868 patients (1,011 ACEI cases and 857 controls) were considered in the meta-analysis. The overall RR of the incident CIN in the ACEI group vs. the control group was 0.95 (95% CI 0.57-1.58), and the total WMDs of the ΔSCr, ΔeGFR and ΔBUN were -0.01 (95% CI -0.04 to 0.02), 5.71 (95% CI -0.66 to 12.09) and 0.78 (95% CI -0.16 to 1.73), respectively. Besides, the RR of CIN incidence in the captopril group vs. the control group was 0.72 (95% CI 0.25-2.05, p = 0.54), and the pooled WMD of the ΔSCr was -0.13 (95% CI -0.21 to -0.06, p < 0.01). Conclusion: This meta-analysis suggests that ACEIs administration has no significant influence in the CIN of patients undergoing coronary angiography or PCI; however, captopril might have the potential to prevent CIN.