WorldWideScience

Sample records for angiotensin-converting enzyme inhibitor

  1. Angiotensin converting enzyme inhibitor induced hyperkalaemic paralysis

    Dutta., D; Fischler, M; McClung, A

    2001-01-01

    Secondary hyperkalaemic paralysis is a rare condition often mimicking the Guillain-Barré syndrome. There have been a few case reports of hyperkalaemia caused by renal failure, trauma, and drugs where the presentation has been with muscle weakness. A case of hyperkalaemic paralysis caused by an angiotensin converting enzyme inhibitor is reported.


Keywords: hyperkalaemia; paralysis; ACE inhibitors

  2. Visceral Angioedema Induced by Angiotensin Converting Enzyme Inhibitor: Case Report

    Beatriz Frutuoso

    2016-05-01

    Conclusion: The diagnosis of intestinal angioedema induced by angiotensin converting enzyme inhibitor can be challenging and time consuming due to its rarity and nonspecific symptoms, which may lead to underdiagnosis of this entity.

  3. Inhibitor and substrate binding by angiotensin-converting enzyme

    Wang, Xuemei; Wu, Shanshan; Xu, Dingguo;

    2011-01-01

    . In this work, we propose a model for an ACE Michaelis complex based on two known X-ray structures of inhibitor-enzyme complexes. Specifically, the human testis angiotensin-converting enzyme (tACE) complexed with two clinic drugs were first investigated using a combined quantum mechanical and molecular......Angiotensin-converting enzyme (ACE) is an important zinc-dependent hydrolase responsible for converting the inactive angiotensin I to the vasoconstrictor angiotensin II and for inactivating the vasodilator bradykinin. However, the substrate binding mode of ACE has not been completely understood...... computational protocol. Implications to ACE catalysis are discussed....

  4. Visceral Angioedema Induced by Angiotensin Converting Enzyme Inhibitor: Case Report

    Beatriz Frutuoso; Joana Esteves; Mafalda Silva; Pedro Gil; Ana Cristina Carneiro; Sílvio Vale

    2016-01-01

    Introduction: Intestinal angioedema is a rare adverse effect of angiotensin converting enzyme inhibitors. Clinical case: A 42-year old woman presented to the Emergency Department complaining of diffuse abdominal pain, predominantly in the right quadrants, with no other associated symptoms. She had been started on perindopril plus indapamide 72 h before the admission for arterial hypertension. There was no other relevant background. Physical examination suggested peritoneal irritation...

  5. Use of angiotensin-converting enzyme inhibitors and cardiovascular outcomes following primary vascular surgery

    Høgh, Annette Langager; Lindholt, Jes S; Nielsen, Henrik;

    2012-01-01

    To examine the association between angiotensin-converting enzyme (ACE) inhibitor use and clinical outcome after primary vascular reconstruction in a population-based follow-up study.......To examine the association between angiotensin-converting enzyme (ACE) inhibitor use and clinical outcome after primary vascular reconstruction in a population-based follow-up study....

  6. Angiotensin-converting enzyme inhibitors in veterinary medicine.

    Lefebvre, H P; Brown, S A; Chetboul, V; King, J N; Pouchelon, J-L; Toutain, P L

    2007-01-01

    Angiotensin-converting enzyme (ACE) inhibitors represent one of the most commonly used categories of drugs in canine and feline medicine. ACE inhibitors currently approved for use in veterinary medicine are benazepril, enalapril, imidapril and ramipril. They are all pro-drugs administered by oral route. A physiologically based model taking into account the saturable binding to ACE has been developed for pharmacokinetic analysis. The bioavailability of the active compounds from their respective pro-drug is low. The active metabolites are eliminated by renal, hepatorenal or biliary excretion, according to the drug. The elimination half-life of the free fraction of the active compounds is very short (ranging from approximately 10 min to 2 h). ACE inhibitors are generally well tolerated. Benazepril, enalapril, imidapril and ramipril are approved for dogs with chronic heart failure (CHF). The efficacy of ACE inhibitors has been convincingly demonstrated in dogs with CHF, especially in those with chronic valvular disease. In such clinical settings, ACE inhibitors improve hemodynamics and clinical signs, and increase survival time. In cats with cardiovascular disease, little information is available except for reports of some benefit in cats with hypertrophic cardiomyopathy in two non-controlled investigations. ACE inhibitors have also a mild to moderate hypotensive effect. There is also evidence to recommend ACE inhibitors in dogs and cats with chronic renal failure (CRF). They decrease the glomerular capillary pressure, have antiproteinuric effects, tend to delay the progression of CRF and to limit the extent of renal lesions. PMID:17506720

  7. Quantum Chemistry Calculation of Angiotensin Converting Enzyme Inhibitors

    2001-01-01

    @@Angiotensin Converting-Enzyme (ACE) inhibitors are potential drugs for hypertension.There are three requirements to be necessary for successful inhibition of ACE:1) a functional group capable of binding to zine in the active site (i.e.carboxylate,phosphonate,or sulfhydryl);2) a carbonyl oxygen capable of accepting a hydryogen bond from some donor residue functional groups and 3) an ionizable C-terminal carboxylate moiety which interacts with positively charged residue〔1〕. We reported active conformers of some ACE inhibitor molecules,which were derived by Distance Comparison〔2〕.In this paper,the electronic structure of the lowest energy conformers and active conformers of the ACE inhibitor molecules (Figure 1) were calculated through ab initio calculation by using Gaussian94 package.The Density Functional Theory (DFT) method and 6-31G** basis set were used 〔3〕.The calculation results were listed in Table 1.The total energies、HOMO energies and the charges of the marked atoms of all active conformers were higher than that of the correspondent lowest energy conformers.They were useful clues for designing novel analogs to inhibit the activity of ACE.

  8. Angiotensin-Converting Enzyme Inhibitors and Active Tuberculosis

    Wu, Jiunn-Yih; Lee, Meng-Tse Gabriel; Lee, Si-Huei; Lee, Shih-Hao; Tsai, Yi-Wen; Hsu, Shou-Chien; Chang, Shy-Shin; Lee, Chien-Chang

    2016-01-01

    Abstract Numerous epidemiological data suggest that the use of angiotensin-converting enzyme inhibitors (ACEis) can improve the clinical outcomes of pneumonia. Tuberculosis (TB) is an airborne bacteria like pneumonia, and we aimed to find out whether the use of ACEis can decrease the risk of active TB. We conducted a nested case–control analysis by using a 1 million longitudinally followed cohort, from Taiwan national health insurance research database. The rate ratios (RRs) for TB were estimated by conditional logistic regression, and adjusted using a TB-specific disease risk score (DRS) with 71 TB-related covariates. From January, 1997 to December, 2011, a total of 75,536 users of ACEis, and 7720 cases of new active TB were identified. Current use (DRS adjusted RR, 0.87 [95% CI, 0.78–0.97]), but not recent and past use of ACEis, was associated with a decrease in risk of active TB. Interestingly, it was found that chronic use (>90 days) of ACEis was associated with a further decrease in the risk of TB (aRR, 0.74, [95% CI, 0.66–0.83]). There was also a duration response effect, correlating decrease in TB risk with longer duration of ACEis use. The decrease in TB risk was also consistent across all patient subgroups (age, sex, heart failure, cerebrovascular diseases, myocardial infraction, renal diseases, and diabetes) and patients receiving other cardiovascular medicine. In this large population-based study, we found that subjects with recent and chronic use of ACEis were associated with decrease in TB risk. PMID:27175655

  9. Angiotensin Converting Enzyme (ACE) Inhibitor Extends Caenorhabditis elegans Life Span.

    Kumar, Sandeep; Dietrich, Nicholas; Kornfeld, Kerry

    2016-02-01

    Animal aging is characterized by progressive, degenerative changes in many organ systems. Because age-related degeneration is a major contributor to disability and death in humans, treatments that delay age-related degeneration are desirable. However, no drugs that delay normal human aging are currently available. To identify drugs that delay age-related degeneration, we used the powerful Caenorhabditis elegans model system to screen for FDA-approved drugs that can extend the adult lifespan of worms. Here we show that captopril extended mean lifespan. Captopril is an angiotensin-converting enzyme (ACE) inhibitor used to treat high blood pressure in humans. To explore the mechanism of captopril, we analyzed the acn-1 gene that encodes the C. elegans homolog of ACE. Reducing the activity of acn-1 extended the mean life span. Furthermore, reducing the activity of acn-1 delayed age-related degenerative changes and increased stress resistance, indicating that acn-1 influences aging. Captopril could not further extend the lifespan of animals with reduced acn-1, suggesting they function in the same pathway; we propose that captopril inhibits acn-1 to extend lifespan. To define the relationship with previously characterized longevity pathways, we analyzed mutant animals. The lifespan extension caused by reducing the activity of acn-1 was additive with caloric restriction and mitochondrial insufficiency, and did not require sir-2.1, hsf-1 or rict-1, suggesting that acn-1 functions by a distinct mechanism. The interactions with the insulin/IGF-1 pathway were complex, since the lifespan extensions caused by captopril and reducing acn-1 activity were additive with daf-2 and age-1 but required daf-16. Captopril treatment and reducing acn-1 activity caused similar effects in a wide range of genetic backgrounds, consistent with the model that they act by the same mechanism. These results identify a new drug and a new gene that can extend the lifespan of worms and suggest new

  10. Angiotensin Converting Enzyme (ACE Inhibitor Extends Caenorhabditis elegans Life Span.

    Sandeep Kumar

    2016-02-01

    Full Text Available Animal aging is characterized by progressive, degenerative changes in many organ systems. Because age-related degeneration is a major contributor to disability and death in humans, treatments that delay age-related degeneration are desirable. However, no drugs that delay normal human aging are currently available. To identify drugs that delay age-related degeneration, we used the powerful Caenorhabditis elegans model system to screen for FDA-approved drugs that can extend the adult lifespan of worms. Here we show that captopril extended mean lifespan. Captopril is an angiotensin-converting enzyme (ACE inhibitor used to treat high blood pressure in humans. To explore the mechanism of captopril, we analyzed the acn-1 gene that encodes the C. elegans homolog of ACE. Reducing the activity of acn-1 extended the mean life span. Furthermore, reducing the activity of acn-1 delayed age-related degenerative changes and increased stress resistance, indicating that acn-1 influences aging. Captopril could not further extend the lifespan of animals with reduced acn-1, suggesting they function in the same pathway; we propose that captopril inhibits acn-1 to extend lifespan. To define the relationship with previously characterized longevity pathways, we analyzed mutant animals. The lifespan extension caused by reducing the activity of acn-1 was additive with caloric restriction and mitochondrial insufficiency, and did not require sir-2.1, hsf-1 or rict-1, suggesting that acn-1 functions by a distinct mechanism. The interactions with the insulin/IGF-1 pathway were complex, since the lifespan extensions caused by captopril and reducing acn-1 activity were additive with daf-2 and age-1 but required daf-16. Captopril treatment and reducing acn-1 activity caused similar effects in a wide range of genetic backgrounds, consistent with the model that they act by the same mechanism. These results identify a new drug and a new gene that can extend the lifespan of worms

  11. Angiotensin-converting enzyme

    Sørensen, P G; Rømer, F K; Cortes, D

    1984-01-01

    In order to evaluate bleomycin-associated lung damage in humans, lung function parameters and serum levels of the endothelial-bound angiotensin-converting enzyme (ACE) were determined by serial measurements in 11 patients who were treated for testicular cancer. None developed clinical or radiolog......In order to evaluate bleomycin-associated lung damage in humans, lung function parameters and serum levels of the endothelial-bound angiotensin-converting enzyme (ACE) were determined by serial measurements in 11 patients who were treated for testicular cancer. None developed clinical or...

  12. Cricothyroidotomy in a angiotensin-converting enzyme (ACE Inhibitor tongue´s angioedema.

    Acle-Cervera L, Morales-Angulo C, García-Zornoza R, Rubio Suárez A

    2013-01-01

    Full Text Available Hereditary angioedema by inhibitors of Angiotensin Converting Enzyme(ACE is a very rare disorder. It usually affects the upper airway mucosa andproduce rapidly evolving acute exacerbations requiring urgent treatment.We repost the case of a patient being treated with ACE inhibitors and anreview of prevalence, pathophysiology and management of angioedemawith ACE inhibitors for treatment and the latest treatments.

  13. SARTANS AND ANGIOTENSIN CONVERTING ENZYME INHIBITORS: A DUEL BETWEEN TWO LEADERS OF PHARMACOTHERAPY OF CARDIOVASCULAR DISEASES

    K. A. Gyamdzhyan; M. L. Maksimov

    2015-01-01

    Topical issues of cardiovascular disease pharmacotherapy influencing function of the renin-angiotensin-aldosterone system are discussed. Efficacy and safety of two major cardiovascular drug classes, angiotensin converting enzyme inhibitors and sartans, are compared. Data from evidence base of the both drug classes are presented.

  14. Postanesthetic Severe Oral Angioedema in Patient’s Taking Angiotensin-Converting Enzyme Inhibitor

    Acílio Marques

    2014-01-01

    Full Text Available Angiotensin-converting enzyme (ACE inhibitors are the leading cause of a drug-induced angioedema. This occurrence is frequently underdiagnosed, but its relapse can be life-threatening. The authors’ intention in reporting this clinical case is to sound a warning about reviewing attitudes and surveillance to try to improve patient perioperative safety.

  15. Trends in co-prescribing of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in Ireland.

    Wan Md Adnan, Wan A H

    2011-03-01

    (i) To examine the trends in co-prescribing of angiotensin converting enzyme inhibitor (ACEI) and angiotensin-II receptor blocker (ARB) therapy and (ii) to examine the influence of major clinical trials (CALM, COOPERATE, VALIANT and ONTARGET) on co-prescribing.

  16. SARTANS AND ANGIOTENSIN CONVERTING ENZYME INHIBITORS: A DUEL BETWEEN TWO LEADERS OF PHARMACOTHERAPY OF CARDIOVASCULAR DISEASES

    K. A. Gyamdzhyan

    2015-12-01

    Full Text Available Topical issues of cardiovascular disease pharmacotherapy influencing function of the renin-angiotensin-aldosterone system are discussed. Efficacy and safety of two major cardiovascular drug classes, angiotensin converting enzyme inhibitors and sartans, are compared. Data from evidence base of the both drug classes are presented.

  17. THE ANGIOTENSIN CONVERTING-ENZYME-INHIBITOR PERINDOPRIL IMPROVES SURVIVAL AFTER EXPERIMENTAL MYOCARDIAL-INFARCTION IN PIGS

    TOBE, TJM; DELANGEN, CDJ; WEERSINK, EGL; VANWIJNGAARDEN, J; BEL, KJ; DEGRAEFF, PA; VANGILST, WH; WESSELING, H

    1992-01-01

    In this randomized, blinded study the effect of the angiotensin converting enzyme inhibitor perindopril on electrical stability after myocardial infarction in pigs was compared to placebo. The left anterior descending artery was occluded for 45 min. Perindoprilat (0.06 mg/kg, n = 12) or saline (n =

  18. A population-based study of the drug interaction between clopidogrel and angiotensin converting enzyme inhibitors

    Cressman, Alex M; Macdonald, Erin M.; Fernandes, Kimberly A.; Gomes, Tara; Paterson, J. Michael; Muhammad M Mamdani; Juurlink, David N.; ,

    2015-01-01

    Aims Clopidogrel and angiotensin converting enzyme (ACE) inhibitors are commonly co-prescribed drugs. Clopidogrel inhibits carboxylesterase 1 (CES1), the enzyme responsible for converting prodrug ACE inhibitors (such as ramipril and perindopril) to their active metabolites. The clinical implications of this potential drug interaction are unknown. The clinical consequences of the potential drug interaction between clopidogrel and prodrug ACE inhibitors were examined. Methods We conducted a nes...

  19. The effect of an angiotensin converting enzyme inhibitor, ramipril, on bronchial responses to inhaled histamine and bradykinin in asthmatic subjects.

    Dixon, C M; Fuller, R W; Barnes, P J

    1987-01-01

    The effect of a potent inhibitor of angiotensin-converting enzyme, ramipril, was studied on both inhaled histamine and bradykinin-induced bronchoconstriction in six male, normotensive, mild asthmatic subjects. Oral administration of 10 mg ramipril caused no change in lung function or airway reactivity to inhaled histamine or bradykinin despite achieving adequate reduction in angiotensin-converting enzyme activity.

  20. Pneumonia Risk and Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers

    Liu, Chia-Lin; Shau, Wen-Yi; Chang, Chia-Hsuin; Wu, Chi-Shin; Lai, Mei-Shu

    2013-01-01

    Background Recent studies have shown that use of angiotensin-converting enzyme (ACE) inhibitors may decrease pneumonia risk in various populations. We investigated the effect of ACE inhibitors and angiotensin II receptor blockers (ARBs) on pneumonia hospitalization in the general population of Taiwan. Methods We conducted a case-crossover study using the Taiwan Longitudinal Health Insurance Database for the year 2005. Data from patients hospitalized for the first time for pneumonia during 199...

  1. Association of angiotensin-converting enzyme inhibitor therapy and comorbidity in diabetes: results from the Vermont diabetes information system

    MacLean Charles D; Ramos-Nino Maria E; Littenberg Benjamin

    2008-01-01

    Abstract Background Angiotensin converting enzyme inhibitors (ACE inhibitors) reduce peripheral vascular resistance via blockage of angiotensin converting enzyme (ACE). ACE inhibitors are commonly used to treat congestive heart failure and high blood pressure, but other effects have been reported. In this study, we explored the association between ACE inhibitor therapy and the prevalence of comorbid conditions in adults with diabetes Methods We surveyed 1003 adults with diabetes randomly sele...

  2. Association between Angiotensin-Converting Enzyme Inhibitors and Troponin in Acute Coronary Syndrome

    Luiz Minuzzo

    2014-12-01

    Full Text Available Background: Cardiovascular disease is the leading cause of mortality in the western world and its treatment should be optimized to decrease severe adverse events. Objective: To determine the effect of previous use of angiotensin-converting enzyme inhibitors on cardiac troponin I measurement in patients with acute coronary syndrome without ST-segment elevation and evaluate clinical outcomes at 180 days. Methods: Prospective, observational study, carried out in a tertiary center, in patients with acute coronary syndrome without ST-segment elevation. Clinical, electrocardiographic and laboratory variables were analyzed, with emphasis on previous use of angiotensin-converting enzyme inhibitors and cardiac troponin I. The Pearson chi-square tests (Pereira or Fisher's exact test (Armitage were used, as well as the non-parametric Mann-Whitney's test. Variables with significance levels of 0.5 ng / mL were high blood glucose at admission (p = 0.0034 and ST-segment depression ≥ 0.5 mm in one or more leads (p = 0.0016. The use of angiotensin-converting inhibitors prior to hospitalization was associated with troponin ≤ 0.5 ng / mL (p = 0.0482. The C-statistics for this model was 0.77. Conclusion: This study showed a correlation between prior use of angiotensin-converting enzyme inhibitors and reduction in the myocardial necrosis marker troponin I in patients admitted for acute coronary syndrome without ST-segment elevation. However, there are no data available yet to state that this reduction could lead to fewer severe clinical events such as death and re-infarction at 180 days.

  3. Pharmacogenetic risk stratification in angiotensin-converting enzyme inhibitor-treated patients with congestive heart failure

    Nelveg-Kristensen, Karl Emil; Busk Madsen, Majbritt; Torp-Pedersen, Christian;

    2015-01-01

    SNPs of the angiotensin-converting enzyme gene (rs4343) and ABO blood group genes (rs495828 and rs8176746). METHODS: Danish patients with CHF enrolled in the previously reported Echocardiography and Heart Outcome Study were included. Subjects were genotyped and categorized according to pharmacogenetic......BACKGROUND: Evidence for pharmacogenetic risk stratification of angiotensin-converting enzyme inhibitor (ACEI) treatment is limited. Therefore, in a cohort of ACEI-treated patients with congestive heart failure (CHF), we investigated the predictive value of two pharmacogenetic scores that...... previously were found to predict ACEI efficacy in patients with ischemic heart disease and hypertension, respectively. Score A combined single nucleotide polymorphisms (SNPs) of the angiotensin II receptor type 1 gene (rs275651 and rs5182) and the bradykinin receptor B1 gene (rs12050217). Score B combined...

  4. THE CAPABILITIES OF ANGIOTENSIN CONVERTING ENZYME INHIBITORS IN CLINICAL PRACTICE: FOCUS ON VASOPROTECTION

    D. B. Nebieridze

    2015-12-01

    Full Text Available Data of large-scale research that shows comprehensive abilities of an angiotensin converting enzyme (ACE inhibitors in clinical practice were represented. The traditional usage of ACE inhibitors in patients with arterial hypertension and chronic heart failure has extended recently. The study results demonstrate the efficacy of ACE inhibitors in slowing down of disease progression related to atherosclerosis and prove the possibility of a new clinical approach. Evidences support new strategic abilities of a number of ACE inhibitors (ramipril, perindopril, which are associated with vasoprotection.

  5. THE CAPABILITIES OF ANGIOTENSIN CONVERTING ENZYME INHIBITORS IN CLINICAL PRACTICE: FOCUS ON VASOPROTECTION

    D. B. Nebieridze

    2007-01-01

    Full Text Available Data of large-scale research that shows comprehensive abilities of an angiotensin converting enzyme (ACE inhibitors in clinical practice were represented. The traditional usage of ACE inhibitors in patients with arterial hypertension and chronic heart failure has extended recently. The study results demonstrate the efficacy of ACE inhibitors in slowing down of disease progression related to atherosclerosis and prove the possibility of a new clinical approach. Evidences support new strategic abilities of a number of ACE inhibitors (ramipril, perindopril, which are associated with vasoprotection.

  6. The effect of angiotensin-converting-enzyme inhibitors on progression of advanced polycystic kidney disease

    Jafar, Tazeen H; Stark, Paul C; Schmid, Christopher H;

    2005-01-01

    BACKGROUND: It is not known whether angiotensin-converting-enzyme (ACE) inhibitors slow the progression of polycystic kidney disease (PKD). We performed a patient-level meta-analysis to compare the effect of antihypertensive regimens, including ACE inhibitors, to those without ACE inhibitors...... of doubling of baseline serum creatinine or onset of kidney failure). We also performed multivariable linear regression and Cox proportional hazards analyses. Based on previous findings, we searched for interactions between the treatment effect (effect of ACE inhibitors vs. controls) and baseline urine...... protein excretion in both models. RESULTS: Eight studies included a total of 142 subjects with PKD: 68 (48%) were randomized to ACE inhibitors and 74 (52%) were randomized to the control. Baseline mean (SD) urine protein excretion was 0.92 (1.40) g/day: 1.08 (1.50) g/day in the ACE inhibitor and 0.76 (1...

  7. Angiotensin converting enzyme (ACE) inhibitors and renal function. A review of the current status

    Kamper, A L

    1991-01-01

    Angiotensin converting enzyme (ACE) inhibitors are well established in the treatment of hypertension and cardiac failure. Experimental studies in rats have suggested that these agents may protect renal function in chronic nephropathy by a mechanism other than simply lowering the systemic blood...... pressure. In human studies of incipient diabetic nephropathy, worsening of microalbuminuria was prevented during 3 years of ACE inhibition. ACE inhibitors reduce arterial blood pressure in chronic nephropathy, and may cause a fall in glomerular filtration rate. In diabetic nephropathy, proteinuria...... was reduced by 2 months' treatment with enalapril to less than half of the values obtained in a control group treated with metoprolol. Nonrandomised trials have suggested that ACE inhibitors may slow the deterioration of renal function, but no comparisons with other antihypertensive agents in prospective...

  8. Isolation of an angiotensin converting enzyme (ACE) inhibitor from Olea europea and Olea lancea

    Hansen, K; Adsersen, A.; Brøgger Christensen, S.;

    1996-01-01

    The aqueous extract of the leaves of Olea europea and Olea lancea both inhibited Angiotensin Converting Enzyme (ACE) in vitro. A bioassay-directed fractionation resulted in the isolation of a strong ACE-inhibitor namely the secoiridoid 2-(3,4-dihydroxyphenyl)ethyl 4-formyl-3-(2-oxoethyl)-4E...... have not been described previously in the literature as inhibitors of ACE. Oleacin showed a low toxicity in the brine shrimp (Artemia salina) lethality test (LC50(24 h) = 969 ppm).......-hexenoate (oleacin)(IC50 = 26 myM). Five secoiridoid glucosides (oleuropein, ligstroside, excelsioside, oleoside 11-methyl ester, oleoside) isolated from Oleaceous plants showed no significant ACE-inhibition whereas, after enzymatic hydrolysis, the ACE-inhibition at 0.33 mg/ml was between 64% to 95%. Secoiridoids...

  9. ANGIOTENSIN CONVERTING ENZYME INHIBITORS IN ACUTE MYOCARDIAL INFARCTION: WHEN TO START THERAPY AND WHICH DRUG TO USE?

    S. Y. Martsevich; S. N. Tolpygina

    2015-01-01

    Data of studies devoted to application of angiotensin converting enzyme (ACE) inhibitors in acute myocardial infarction are reviewed. The reasons of ambiguous results are discussed. A point of view that different ACE inhibitors may have the various efficacy and safety in patients with acute myocardial infarction is suggested.

  10. Prognostic impact of carboxylesterase 1 gene variants in patients with congestive heart failure treated with angiotensin-converting enzyme inhibitors

    Nelveg-Kristensen, Karl E.; Madsen, Majbritt B.; Torp-Pedersen, Christian;

    2016-01-01

    OBJECTIVE: Most angiotensin-converting enzyme inhibitors (ACEIs) are prodrugs activated by carboxylesterase 1 (CES1). We investigated the prognostic importance of CES1 gene (CES1) copy number variation and the rs3815583 single-nucleotide polymorphism in CES1 among ACEI-treated patients with conge...

  11. [A Case of Life-Threatening Angioedema Occurred During Prolonged Angiotensin-Converting Enzyme Inhibitor Treatment].

    Nakamura, Rintaro; Nihei, Shun-Ichi; Arai, Hideaki; Nagata, Keiji; Isa, Yasuki; Harayama, Nobuya; Aibara, Keiji; Kamochi, Msayuki

    2016-03-01

    Although angiotensin-converting enzyme (ACE) inhibitors are widely used as the first choice drug for treating hypertension, we have only a superficial understanding of their relationship to angioedema. We report a case of life-threatening angioedema. The case was a 60-year-old man who had been taking an ACE inhibitor for hypertension for 11 years. He visited his home doctor for dyspnea, and tongue and neck swelling. He was transported to our hospital because of the possibility of airway obstruction. On admission, his tongue and neck swelling became more severe. We performed an intubation using an endoscope and started airway management. We also stopped his ACE inhibitor. The severe tongue and neck swelling improved gradually and he was extubated on day 3. On the fifth day he was discharged. We diagnosed angioedema caused by an ACE inhibitor. Although the risk of airway obstruction with ACE inhibitors is acknowledged, we have only a superficial understanding of how prolonged ACE inhibitor treatment induces angioedema. So we should consider angioedema in cases of taking ACE inhibitors, especially in cases of prolonged treatment. PMID:26972946

  12. Impact of disease states on the pharmacokinetics and pharmacodynamics of angiotensin-converting enzyme inhibitors.

    LeBlanc, Jaclyn M; Dasta, Joseph F; Pruchnicki, Maria C; Schentag, Jerome J

    2006-09-01

    The pharmacokinetics and pharmacodynamics of angiotensin-converting enzyme inhibitors (ACE) in elderly patients and patients with renal and hepatic impairment were examined, and a role for an AUC/EC50 ratio to guide dosing was evaluated. A Medline and International Pharmaceutical Abstracts search was used to identify human studies and abstracts. Relevant data were evaluated and summarized. Dosing regimens were compared using an AUC/EC50 ratio. Most studies evaluating ACE inhibitors in renal impairment report a strong linear correlation between creatine clearance and drug elimination. AUC and EC50 values for these drugs in elderly subjects appear similar to younger and hypertensive patients. There is increased AUC in some patients with hepatic impairment. Pharmacodynamic data are conflicting. Prolonged ACE inhibition is evident in renal impairment but not necessarily other disease states. ACE inhibitor dosing for hypertension is reasonable based on pharmacokinetics and EC50 values. Further individualization of therapy may improve outcomes, and using the threshold AUC/EC50 ratio may help guide appropriate dosing. PMID:16920891

  13. Radiation-induced pulmonary endothelial dysfunction in rats: modification by an inhibitor of angiotensin converting enzyme

    The ability of the angiotensin converting enzyme (ACE) inhibitor Captopril to modify radiation-induced pulmonary endothelial dysfunction was determined in male rats sacrificed 2 months after a single dose of 10-30 Gy of 60Co gamma rays to the right hemithorax. Half of each dose group consumed feed containing 0.12% w/w Captopril (60 mg/kg/day) continuously after irradiation, and half consumed control feed. Four markers of endothelial function were monitored: ACE activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. All data were plotted as dose-response curves, and subjected to linear regression analysis. The Captopril modifying effect was expressed as the ratio of isoeffective doses at a common intermediate response (DRF), or as the ratio of the response curve slopes. Right lung ACE and PLA activity decreased linearly, and PGI2 and TXA2 production increased linearly with increasing radiation dose. Captopril exhibited DRF values of 1.4-2.1, and slope ratios of 1.4-5.1 for all four functional markers (p less than 0.05). Thus, the ACE inhibitor Captopril ameliorates radiation-induced pulmonary endothelial dysfunction in rats sacrificed 2 months postirradiation. Although the mechanism of Captopril action is not clear at present, these data suggest a novel application for this class of compounds as injury-modifying agents in irradiated lung

  14. Angiotensin Converting Enzyme Inhibitor-related Angioedema: A Case of an Unexpected Death

    Eray Atalay

    2015-11-01

    Full Text Available Angioedema is an asymmetric non-pitting oedema on face, lips, tongue and mucous membranes; any delay in diagnosis and treatment can be fatal. Treatment with lisinopril as an angiotensin converting enzyme (ACE inhibitor, can be a reason of angioedema. Here we report a case who developed oral-facial edema four years after using lisinopril/hydrochlorothiazide. Laryngeal oedema is a main cause of death in angioedema. The treatment of choice in angioedema including fresh frozen plasma, C1 inhibitor concentrations and BRK-2 antagonists (bradykinin B2 receptor antagonists were used. In this case; a 77 years old female patient suffering from hypertension was considered. This patient was suffering two days from swelling on her face and neck. Non- allergic angioedema was distinguished in five major forms; acquired (AAO, hereditary (HAE, renin-angiotensin-aldosterone system (RAAS blocker-dependent, pseudoallergic angioedema (PAS and an idiopathic angioedema (IAO. She was admitted to our clinic with the diagnosis of hereditary angioedema. Patient had skin edema and life threatening laryngeal edema. In emergency department treatment was started using intravenous methylprednisolone, diphenydramine as well as inhaled and subcutaneous epinephrine simultaneously. Despite the initial treatment, the patient died due to the insufficient respiration and cardiac arrest. The patient has no history of kidney disease.

  15. Angiotensin Converting Enzyme Inhibitor-related Angioedema: A Case of an Unexpected Death.

    Atalay, Eray; Özdemir, Mehmet Tamer; Çiğsar, Gülşen; Omurca, Ferhat; Aslan, Nurullah; Yildiz, Mehmet; Gey, Zehra Bahar

    2015-11-01

    Angioedema is an asymmetric non-pitting oedema on face, lips, tongue and mucous membranes; any delay in diagnosis and treatment can be fatal. Treatment with lisinopril as an angiotensin converting enzyme (ACE) inhibitor, can be a reason of angioedema. Here we report a case who developed oral-facial edema four years after using lisinopril/hydrochlorothiazide. Laryngeal oedema is a main cause of death in angioedema. The treatment of choice in angioedema including fresh frozen plasma, C1 inhibitor concentrations and BRK-2 antagonists (bradykinin B2 receptor antagonists) were used. In this case; a 77 years old female patient suffering from hypertension was considered. This patient was suffering two days from swelling on her face and neck. Non- allergic angioedema was distinguished in five major forms; acquired (AAO), hereditary (HAE), renin-angiotensin-aldosterone system (RAAS) blocker-dependent, pseudoallergic angioedema (PAS) and an idiopathic angioedema (IAO). She was admitted to our clinic with the diagnosis of hereditary angioedema. Patient had skin edema and life threatening laryngeal edema. In emergency department treatment was started using intravenous methylprednisolone, diphenydramine as well as inhaled and subcutaneous epinephrine simultaneously. Despite the initial treatment, the patient died due to the insufficient respiration and cardiac arrest. The patient has no history of kidney disease. PMID:26725563

  16. Verapamil and angiotensin-converting enzyme inhibitors in patients with coronary artery disease and reduced left ventricular ejection fraction

    Hansen, J F; Tingsted, L; Rasmussen, Verner;

    1996-01-01

    Verapamil is effective as antianginal medication but contraindicated in patients with congestive heart failure. Angiotensin-converting enzyme (ACE) inhibitors improve survival in patients with congestive heart failure but have limited effect on patients with angina pectoris. No studies have been...... published on the combined treatment with verapamil and ACE inhibitors in patients with stable angina pectoris and left ventricular dysfunction. We performed an open study in 14 patients with angina pectoris and ejection fraction

  17. Estimation of angiotensin-converting enzyme inhibitors protein binding degree using chromatographic hydrophobicity data

    Trbojević-Stanković Jasna

    2015-01-01

    Full Text Available Introduction. Angiotensin-converting enzyme (ACE inhibitors represent a significant group of drugs primarily used in the treatment of hypertension and congestive heart failure. Objective. Selected ACE inhibitors (enalapril, quinapril, fosinopril, lisinopril, cilazapril were studied in order to establish a fast and easy estimation method of their plasma protein binding degree based on their lipophilicity data. Methods. Chromatographic hydrophobicity data (parameter C0 were obtained on cellulose layers under conditions of normal-phase thin-layer chromatography (NPTLC, using different binary solvent systems. The ACE inhibitors lipophilicity descriptors (logP values were calculated using the software package Virtual Computational Chemistry Laboratory. The ACE inhibitors plasma protein binding data were collected from relevant literature. Results. ACE inhibitors protein binding data varied from negligible (lisinopril to 99% (fosinopril. The calculated lipophilicity descriptors, logPKOWWIN values ranged from -0.94 (lisinopril to 6.61 (fosinopril. Good correlations were established between plasma protein binding values and calculated logPKOWWIN values (R2=0.8026 as well as chromatographic hydrophobicity data, C0 parameters (R2=0.7662. Even though good correlation coefficients (R2 were obtained in both relations, unacceptable probability value with p>0.05 was found in relation between protein binding data and calculated logPKOWWIN values. Subsequently, taking into consideration the request for probability value lower than 0.05, a better relationship was observed between protein binding data and chromatographically obtained hydrophobicity parameters C0 values. Conclusion. Cellulose layers are easily available and cost effective sorbent to assess hydrophobicity. Experimentally obtained data on ACE inhibitors hydrophobicity and plasma protein binding estimation are important parameters in evaluating bioavailability of these drugs. [Projekat Ministarstva

  18. Search for potential angiotensin converting enzyme (ACE)-inhibitors from plants.

    Lacaille-Dubois; Franck, U; Wagner, H

    2001-01-01

    MeOH extracts, fractions and pure substances from Musanga cecropioides, Cecropia species and Crataegus oxyacantha /C. monogyna were screened by using an in vitro bio-assay based on the inhibition of Angiotensin Converting Enzyme (ACE), as measured from the enzymatic cleavage of the chromophore-fluorophore-labelled substrate dansyltriglycine into dansylglycine and diglycine. Phenolic acids showed no significant ACE-inhibition whereas flavonoids and proanthocyanidins demonstrated inhibitory activity at 0.33 mg/ml using this test system. PMID:11292239

  19. Effects of Angiotensin Converting Enzyme Inhibitors on Liver Fibrosis in HIV and Hepatitis C Coinfection

    Lindsey J. Reese

    2012-01-01

    Full Text Available Background. Liver fibrosis is accelerated in HIV and hepatitis C coinfection, mediated by profibrotic effects of angiotensin. The objective of this study was to determine if angiotensin converting enzyme inhibitors (ACE-Is attenuate liver fibrosis in coinfection. Methods. A retrospective review of 156 coinfected subjects was conducted to analyze the association between exposure to ACE-Is and liver fibrosis. Noninvasive indices of liver fibrosis (APRI, FIB-4, Forns indices were compared between subjects who had taken ACE-Is and controls who had not taken them. Linear regression was used to evaluate ACE-I use as an independent predictor of fibrosis. Results. Subjects taking ACE-Is for three years were no different than controls on the APRI and the FIB-4 but had significantly higher scores than controls on the Forns index, indicating more advanced fibrosis. The use of ACE-Is for three years remained independently associated with an elevated Forns score when adjusted for age, race, and HIV viral load (P<0.001. There were significant associations between all of the indices and significant fibrosis, as determined clinically and radiologically. Conclusions. There was not a protective association between angiotensin inhibition and liver fibrosis in coinfection. These noninvasive indices may be useful for ruling out significant fibrosis in coinfection.

  20. [Psychotropic effects of angiotensin-converting enzyme inhibitors: what are the arguments?].

    Mesure, G; Fallet, A; Chevalier, J F

    1995-01-01

    The authors report a case of acute mania induced by perindopril (Coversyl) in a 57 year old man with no prior history of mental illness. This Angiotensin-Converting Enzyme Inhibitor (ACEI) had been introduced eight days prior to the first signs of excitation, in order to treat recently diagnosed arterial hypertension. Without proof of reintroduction, and on the basis of clinical observations, the attribution appears plausible. Similar observations have been made for other molecules in this class of medication, such as captopril (Lopril). A review of literature regroups recent data concerning psychotropic effects of ACEIs. Several reports claim that captopril clearly acts as an antidepressant. Studies on the mood or the quality of life of treated hypertensive patients show ACEIs to have an euphoric-type positive effect compared to other anti-hypertensive treatments. Captopril and perindopril also act like potential antidepressants in experimental models of antidepression. Furthermore, pharmacologic data confirm that the most lipophilic ACEIs penetrate the central nervous system and argue in favor of the role of these molecules in activating central opioides. As these data provide evidence of mood swing in some patients, but also of an overall benefit in hypertensive populations, the clinical importance of the antidepressant effect of ACEIs needs further investigations. PMID:8529571

  1. CES1 genetic variation affects the activation of angiotensin-converting enzyme inhibitors.

    Wang, X; Wang, G; Shi, J; Aa, J; Comas, R; Liang, Y; Zhu, H-J

    2016-06-01

    The aim of the study was to determine the effect of carboxylesterase 1 (CES1) genetic variation on the activation of angiotensin-converting enzyme inhibitor (ACEI) prodrugs. In vitro incubation study of human liver, intestine and kidney s9 fractions demonstrated that the ACEI prodrugs enalapril, ramipril, perindopril, moexipril and fosinopril are selectively activated by CES1 in the liver. The impact of CES1/CES1VAR and CES1P1/CES1P1VAR genotypes and diplotypes on CES1 expression and activity on enalapril activation was investigated in 102 normal human liver samples. Neither the genotypes nor the diplotypes affected hepatic CES1 expression and activity. Moreover, among several CES1 nonsynonymous variants studied in transfected cell lines, the G143E (rs71647871) was a loss-of-function variant for the activation of all ACEIs tested. The CES1 activity on enalapril activation in human livers with the 143G/E genotype was approximately one-third of that carrying the 143G/G. Thus, some functional CES1 genetic variants (for example, G143E) may impair ACEI activation, and consequently affect therapeutic outcomes of ACEI prodrugs. PMID:26076923

  2. Discovery of new angiotensin converting enzyme (ACE) inhibitors from medicinal plants to treat hypertension using an in vitro assay

    Sharifi, Niusha; Souri, Effat; Ziai, Seyed Ali; Amin, Gholamreza; Amanlou, Massoud

    2013-01-01

    Background and purpose of the study Angiotensin converting enzyme (ACE) inhibitors plays a critical role in treating hypertension. The purpose of the present investigation was to evaluate ACE inhibition activity of 50 Iranian medicinal plants using an in vitro assay. Methods The ACE activity was evaluated by determining the hydrolysis rate of substrate, hippuryl-L-histidyl-L-leucine (HHL), using reverse phase high performance liquid chromatography (RP-HPLC). Total phenolic content and antioxi...

  3. The effects of angiotensin-converting enzyme inhibitors on peritoneal protein loss and solute transport in peritoneal dialysis patients

    Taner Basturk

    2012-08-01

    Full Text Available OBJECTIVE: The objective of this study was to examine the effects of angiotensin-converting enzyme inhibitors on peritoneal membrane transport, peritoneal protein loss, and proteinuria in peritoneal dialysis patients. METHODS: Fifty-four peritoneal dialysis patients were included in the study. The patients were divided into two groups. Group 1 (n = 34 was treated with angiotensin-converting enzyme inhibitors. Group 2 (n = 20 did not receive any antihypertensive drugs during the entire follow-up. Eleven patients were excluded from the study thereafter. Thus, a total of 30 patients in Group 1 and 13 patients in Group 2 completed the study. We observed the patients for six months. Group 1 patients received maximal doses of angiotensin-converting enzyme inhibitors for six months. Parameters at the beginning of study and at the end of six months were evaluated. RESULTS: At the end of six months, total peritoneal protein loss in 24-hour dialysate effluent was significantly decreased in Group 1, whereas it was increased in Group 2. Compared to the baseline level, peritoneal albumin loss in 24-hour dialysate effluent and 4-hour D/P creatinine were significantly increased in Group 2 but were not significantly changed in Group 1. A covariance analysis between the groups revealed a significant difference only in the decreased amount of total protein loss in 24-hour dialysate. Proteinuria was decreased significantly in Group 1. CONCLUSION: This study suggests that angiotensin-converting enzyme inhibitors reduce peritoneal protein loss and small-solute transport and effectively protect peritoneal membrane transport in peritoneal dialysis patients.

  4. Mitigation of radiation-induced lung fibrosis by angiotensin converting enzyme inhibitors

    The aim of this study was to test the mitigating potential of angiotensin converting enzyme inhibitors (ACEi) against radiation-induced pulmonary fibrosis, which could result from accidental exposure or radiological terrorism. Rats (WAG/RijCmcr) were exposed to a single dose of 13 Gy of X-irradiation to the whole thorax, at the dose rate of 1.43 Gy/min. Three structurally-different ACEi's, captopril (145-207 mg/m2/day), enalapril (19-28 mg/m2/day) and fosinopril (19-28 mg/m2/day) were administered in drinking water beginning 1 week after whole thoracic irradiation. Rats that survived acute pneumonitis (6-12 weeks) were accessed monthly after irradiation for the effects on lung structure and function. Endpoints included breathing rate, wet:dry weight ratio, collagen content and histolopathological studies. Treatment with captopril or enalapril, but not fosinopril, beginning 1 week after 13 Gy X-irradiation improved survival of rats. Mortality of 30-35% was observed with administration of captopril or enalapril compared to 70% for 13 Gy alone. All three ACEi's attenuated radiation-induced lung fibrosis at 7 months after irradiation based on histological indices and measurement of lung collagen. After whole-thoracic irradiation, ACEi's mitigate radiation induced pulmonary fibrosis based on histological and biochemical endpoints. These treatments were effective even when administration was not started until one week after irradiation. Our findings support the therapeutic potential of ACEi's against chronic radiation induced lung injury. (author)

  5. Angiotensin-Converting Enzyme Inhibitors and Active Tuberculosis: A Population-Based Study.

    Wu, Jiunn-Yih; Lee, Meng-Tse Gabriel; Lee, Si-Huei; Lee, Shih-Hao; Tsai, Yi-Wen; Hsu, Shou-Chien; Chang, Shy-Shin; Lee, Chien-Chang

    2016-05-01

    Numerous epidemiological data suggest that the use of angiotensin-converting enzyme inhibitors (ACEis) can improve the clinical outcomes of pneumonia. Tuberculosis (TB) is an airborne bacteria like pneumonia, and we aimed to find out whether the use of ACEis can decrease the risk of active TB.We conducted a nested case-control analysis by using a 1 million longitudinally followed cohort, from Taiwan national health insurance research database. The rate ratios (RRs) for TB were estimated by conditional logistic regression, and adjusted using a TB-specific disease risk score (DRS) with 71 TB-related covariates.From January, 1997 to December, 2011, a total of 75,536 users of ACEis, and 7720 cases of new active TB were identified. Current use (DRS adjusted RR, 0.87 [95% CI, 0.78-0.97]), but not recent and past use of ACEis, was associated with a decrease in risk of active TB. Interestingly, it was found that chronic use (>90 days) of ACEis was associated with a further decrease in the risk of TB (aRR, 0.74, [95% CI, 0.66-0.83]). There was also a duration response effect, correlating decrease in TB risk with longer duration of ACEis use. The decrease in TB risk was also consistent across all patient subgroups (age, sex, heart failure, cerebrovascular diseases, myocardial infraction, renal diseases, and diabetes) and patients receiving other cardiovascular medicine.In this large population-based study, we found that subjects with recent and chronic use of ACEis were associated with decrease in TB risk. PMID:27175655

  6. Angiotensin-converting enzyme inhibitors - a new paradigm for protecting normal tissue from radiation injury

    Full text: Normal tissue complications after radiation therapy for cancer treatment are rare, but when they occur they can be life threatening or have devastating effects on a patient's quality of life. We present compelling evidence that angiotensin-converting enzyme inhibitors, ACEi, reduce normal tissue injury after radiation exposure. ACEi inhibits the conversion of Ang I to Ang II, a potent vasoactive hormone whose overproduction stimulates a number of cytokines, including TGF-β. Radiation protection is illustrated with results from two tissue models, mouse skin, an early responding tissue and rat optic nerve, a late responding tissue. Mouse hind legs were irradiated to 60Gy in 10 equal fractions over 2 wks. Mice were given 2.5mg/kg/day of ramipril in their drinking water. ACEi treated mice demonstrated significantly less damage than the mice in the non-drug treated, radiation alone group assessed using acute (hair loss), subacute (desquamation), and late endpoints (leg contraction). In a separate study, rat brains were irradiated stereotactically with a single focused beam of 30Gy. Six months after irradiation and 1.5mg/kg/day of ramipril, rats were assessed for optic nerve damage functionally using evoked potential to a light stimulus, structurally using Mn++ contrast-enhanced MRI, and histologically using H and E and Luxol-Fast-Blue stain for myelin. Of note is that all rat groups, including ACEi treated rats demonstrated damaged optic nerve by MRI and histology. Preliminary results indicate that ramipril conferred significant functional radiation protection since rats receiving radiation alone had a two to three times delay in the duration of the visual evoked potential, whereas 75% of rats receiving ramipril and radiation had evoked potentials that resembled that of normal untreated control rats. Our studies are unique and important for at least three reasons. This is the first report of the radiation protective effects of carboxyl-containing ACEi

  7. Angiotensin-converting enzyme inhibitor (enalapril maleate) accelerates recovery of mouse skin from UVB-induced wrinkles

    Matsuura-Hachiya, Yuko; Arai, Koji Y.; Ozeki, Rieko; Kikuta, Ayako; Nishiyama, Toshio, E-mail: toshio_n@cc.tuat.ac.jp

    2013-12-06

    Highlights: •Angiotensin converting enzyme (ACE) increases in UVB-irradiated skin. •Administration of an ACE inhibitor improved UVB-induced skin wrinkle. •ACE inhibitor improved UVB-induced epidermal hypertrophy. •ACE inhibitor improved transepidermal water loss in the UVB-irradiated skin. -- Abstract: Angiotensin-converting enzyme (ACE) activity and angiotensin II signaling regulate cell proliferation, differentiation, and tissue remodeling, as well as blood pressure, while in skin, angiotensin II signaling is involved in wound healing, inflammation, and pathological scar formation. Therefore, we hypothesized that angiotensin II is also involved in photoaging of skin. In this study, we examined the effect of enalapril maleate, an ACE inhibitor, on recovery of wrinkled skin of hairless mice exposed to long-term UVB irradiation. Immunohistochemical observation revealed that expression of ACE, angiotensin II, and angiotensin II type 1 (AT1) and type 2 (AT2) receptors in the skin was increased after UVB irradiation (3 times/week at increasing intensities for 8 weeks). Administration of enalapril maleate (5 times/week for 6 weeks, starting 1 week after 10-week irradiation) accelerated recovery from UVB-induced wrinkles, epidermal hyperplasia and epidermal barrier dysfunction, as compared with the vehicle control. Our results indicate that ACE and angiotensin II activity are involved in skin photoaging, and suggest that ACE inhibitor such as enalapril maleate may have potential for improvement of photoaged skin.

  8. Renal graft failure after addition of an angiotensin II receptor antagonist to an angiotensin-converting enzyme inhibitor

    Kamper, Anne-Lise; Nielsen, Arne Høj; Baekgaard, Niels;

    2002-01-01

    Combined treatment with an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II (Ang II) receptor blocker (ARB) has been suggested in order to achieve a more complete blockade of the renin-angiotensin-aldosterone system in cardiovascular and renal disease. The present report...... describes a case of acute renal graft dysfunction following the addition of an ARB to existing ACE inhibition. This unmasked an unknown iliac artery stenosis. The case indicates a possible important role of Ang II generated by non-ACE pathways in this situation....

  9. Plant Flavonoids as Angiotensin Converting Enzyme Inhibitors in Regulation of Hypertension

    H.P. Vasantha Rupasinghe

    2011-05-01

    Full Text Available Background: Angiotensin converting enzyme (ACE is a key component in the renin angiotensin aldosterone system (RAAS which regulates blood pressure. As the over expression of RAAS is associated with vascular hypertension, ACE inhibition has become a major target control for hypertension. The research on potential ACE inhibitors is expanding broadly and most are focused on natural product derivatives such as peptides, polyphenolics, and terpenes. Plant polyphenolics are antioxidant molecules with various beneficial pharmacological properties. The current study is focused on investigating and reviewing the ACE inhibitory property of fruit flavonoids. An apple skin extract (ASE rich in flavonoids, the major constituents of the extract and their selected metabolites were assessed for the ACE inhibitory property in vitro. It is important to investigate the metabolites along with the flavonoids as they are the constituents active inside the human body.Objective: To investigate whether flavonoids, flavonoid rich apple extracts and their metabolites could inhibit ACE in vitro.Method: The samples were incubated with sodium borate buffer (30 μL, pH 8.3, 150 μL of substrate (Hip-His-Liu and ACE (30 μL at 37 oC for 1 h. The reaction was stopped by addition of 150 μL of 0.3M NaOH. The enzyme cleaved substrate was detected by making a fluorimetricadduct by adding 100 μL of o-phthaladehyde for 10 min at room temperature. Reaction wasstopped by adding 50 μL of 3M HCl. Fluorescence was measured by using a FluoStar Optimaplate reader at excitation of 350 nm and emission of 500 nm.Results: The extract and the compounds showed a concentration dependant enzyme inhibition.Increasing concentrations from 0.001 ppm to 100 ppm of ASE showed an increment of 29% to64% ACE inhibition. The IC50 (concentration of test compound which gives 50% enzymeinhibition values of ASE, quercetin, quercetin-3-glucoside, quercetin-3-galactoside, cyanidin-3-galactoside were 49

  10. Predictors of angiotensin-converting enzyme inhibitor-induced reduction of urinary albumin excretion in nondiabetic patients.

    van de Wal, Ruud M A; Gansevoort, Ron T; van der Harst, Pim; Boomsma, Frans; Thijs Plokker, H W; van Veldhuisen, Dirk J; de Jong, Paul E; van Gilst, Wiek H; Voors, Adriaan A

    2006-11-01

    Urinary albumin excretion is a predictor for cardiovascular mortality and morbidity. We investigated which parameters determine baseline urinary albumin excretion in nondiabetic subjects, without renal disease. In addition, we evaluated the parameters that predict the albuminuria-lowering efficacy of an angiotensin-converting enzyme inhibitor. In this substudy of the Prevention of Renal and Vascular Endstage Disease Intervention Trial, 384 microalbuminuric patients were included. Patient and biochemical characteristics were obtained at baseline and after 3 months of double-blinded, randomized treatment (fosinopril 20 mg or placebo). Mean age was 51.1+/-11.5 years, and 65.6% were male. Median urinary albumin excretion was 22.2 mg per 24 hours. At baseline, mean arterial pressure (beta(standardized)=0.161; P=0.006), urinary sodium excretion (beta(standardized)=0.154; P=0.011), and estimated renal function were independently associated with albumin excretion. In these predominantly normotensive to prehypertensive subjects, fosinopril reduced albumin excretion by 18.5% versus a 6.1% increase on placebo after 3 months (Poutspoken in subjects with higher baseline albumin excretion. Based on our data, we hypothesize that angiotensin-converting enzyme inhibition may result in superior cardiovascular protection when compared with other blood pressure-lowering agents in subjects with higher baseline levels of albuminuria. PMID:17000930

  11. Long-term compliance with beta-blockers, angiotensin-converting enzyme inhibitors, and statins after acute myocardial infarction

    Gislason, Gunnar H; Rasmussen, Jeppe Nørgaard; Abildstrøm, Steen Z;

    2006-01-01

    AIMS: To study initiation, dosages, and compliance with beta-blockers, angiotensin-converting enzyme (ACE)-inhibitors, and statins in patients after acute myocardial infarction (AMI) and to identify likely targets for improvement. METHODS AND RESULTS: Patients admitted with first AMI between 1995...... and 2002 were identified by linking nationwide administrative registers. A total of 55 315 patients survived 30 days after discharge and were included; 58.3% received beta-blockers, 29.1% ACE-inhibitors, and 33.5% statins. After 1, 3, and 5 years, 78, 64, and 58% of survivors who had started therapy were...... still receiving beta-blockers, 86, 78, and 74% were receiving ACE-inhibitors, and 85, 80, and 82% were receiving statins, respectively. Increased age and female sex were associated with improved compliance. The dosages prescribed were generally 50% or less of the dosages used in clinical trials...

  12. Structure elucidation of A58365A and A58365B, angiotensin converting enzyme inhibitors produced by Streptomyces chromofuscus.

    Hunt, A H; Mynderse, J S; Samlaska, S K; Fukuda, D S; Maciak, G M; Kirst, H A; Occolowitz, J L; Swartzendruber, J K; Jones, N D

    1988-06-01

    A58365A and A58365B, angiotensin converting enzyme inhibitors isolated from the culture filtrate of Streptomyces chromofuscus NRRL 15098, are homologous compounds of molecular formulas C12H13NO6 and C13H15NO6. The molecular similarities of the two inhibitors were established by comparison of their 1H NMR, 13C NMR, and UV spectra. Catalytic hydrogenation of A58365A led to a tetrahydro-deoxy derivative, C12H17NO5; extensive 1H NMR decoupling studies at 360 MHz allowed all the non-exchangeable protons of the derivative to be connected in a continuous substructure. This fragment was combined with information from other spectroscopic methods to suggest the structures for A58365A (1) and A58365B (2); the conclusions were confirmed by an X-ray crystallographic analysis of A58365A-dimethyl ester. PMID:3403371

  13. Angiotensin-converting-enzyme inhibitors in stable vascular disease without left ventricular systolic dysfunction or heart failure : a combined analysis of three trials

    Dagenais, Gilles R.; Pogue, Janice; Fox, Kim; Simoons, Marteen L.; Yusuf, Salim

    2006-01-01

    Background Angiotensin-converting-enzyme (ACE) inhibitors reduce cardiovascular mortality and morbidity in patients with heart failure or left ventricular systolic dysfunction (LVSD). Three large trials have assessed the effect of ACE inhibitors in stable patients without these conditions but with a

  14. Angiotensin-converting enzyme inhibitors: measurement of relative inhibitory potency and serum drug levels by radioinhibitor binding displacement assay

    Radioinhibitor binding displacement, a new method for the measurement of angiotensin-converting enzyme (ACE) competitive inhibitors, has been used to assess the relative potency of nine synthetic ACE inhibitors. MK351A, tyrosyl derivative of enalaprilic acid was iodinated with 125I and used as the radioligand. [125I]MK351A bound to human serum ACE in a concentration-dependent manner. It was displaced in a concentration-dependent manner by all ACE inhibitors tested. Fifty percent displacement of bound [125I]MK351A (DD50) for each ACE inhibitor correlated well with inhibitor potency ID50, estimated using an ACE enzymatic activity assay using Hip-His-Leu as substrate (r = 0.96, p less than 0.001; n = 9). The radioinhibitor binding displacement assay was used to measure serum concentration of enalaprilic acid (MK422) in human serum samples. Drug concentration estimated by radioinhibitor binding displacement assay correlated closely (r = 0.96, p less than 0.001; n = 22) with the drug concentration measured by a specific radioimmunoassay. The radioinhibitor binding displacement technique using [125I]MK351A as the ligand for human serum ACE has general application to all competitive ACE inhibitors, allowing comparison of in vitro ACE inhibitor potencies and estimation of serum ACE inhibitor concentrations

  15. The rationale and design of the perindopril genetic association study (PERGENE): A pharmacogenetic analysis of angiotensin-converting enzyme inhibitor therapy in patients with stable coronary artery disease

    J.J. Brugts (Jasper); M.P.M. de Maat (Moniek); H. Boersma (Eric); J.C.M. Witteman (Jacqueline); C.M. van Duijn (Cock); A.G. Uitterlinden (André); M.E. Bertrand (Michel); W.J. Remme (Willem); K.M. Fox (Kim); R. Ferrari (Roberto); A.H.J. Danser (Jan); M.L. Simoons (Maarten)

    2009-01-01

    textabstractBackground: Angiotensin-converting enzyme (ACE) inhibitors reduce clinical symptoms and improve outcome in patients with hypertension, heart failure, and stable coronary artery disease (CAD) and are among the most frequently used drugs in these patient groups. For hypertension, treatment

  16. Genetic determinants of treatment benefit of the angiotensin-converting enzyme-inhibitor perindopril in patients with stable coronary artery disease

    J.J. Brugts (Jasper); A.J. Isaacs (Aaron); H. Boersma (Eric); C.M. van Duijn (Cock); A.G. Uitterlinden (André); W.J. Remme (Willem); M.E. Bertrand (Michel); T. Ninomiya (T.); C. Ceconi (Claudio); J. Chalmers (John); S. MacmMahon (Stephen); K.M. Fox (Kim); R. Ferrari (Roberto); J.C.M. Witteman (Jacqueline); A.H.J. Danser (Jan); M.L. Simoons (Maarten); M.P.M. de Maat (Moniek)

    2010-01-01

    textabstractAims The efficacy of angiotensin-converting enzyme (ACE)-inhibitors in stable coronary artery disease (CAD) may be increased by targeting the therapy to those patients most likely to benefit. However, these patients cannot be identified by clinical characteristics. We developed a genetic

  17. Acute Kidney Injury in Elderly Patients With Chronic Kidney Disease: Do Angiotensin-Converting Enzyme Inhibitors Carry a Risk?

    Chaumont, Martin; Pourcelet, Aline; van Nuffelen, Marc; Racapé, Judith; Leeman, Marc; Hougardy, Jean-Michel

    2016-06-01

    In contrast to angiotensin receptor blockers (ARBs), mainly excreted by the liver, the dosage of angiotensin-converting enzyme (ACE) inhibitors, cleared by the kidney, must be adapted to account for renal clearance in patients with chronic kidney disease (CKD) to avoid acute kidney injury (AKI). Community-acquired AKI and the use of ACE inhibitors or ARBs in the emergency department were retrospectively assessed in 324 patients with baseline stage 3 or higher CKD. After stepwise regression analysis, the use of ACE inhibitors (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.1; P=.02) and the presence of dehydration (OR, 30.8; 95% CI, 3.9-239.1) were associated with AKI. A total of 45% of patients using ACE inhibitors experienced overdosing, which causes most of the excess risk of AKI. These results suggest that dosage adjustment of ACE inhibitors to renal function or substitution of ACE inhibitors with ARBs could reduce the incidence of AKI. Moreover, ACE inhibitors and ARBs should be stopped in cases of dehydration. PMID:27080620

  18. Preoperative angiotensin converting enzyme inhibitor usage in patients with chronic subdural hematoma: Associations with initial presentation and clinical outcome.

    Neidert, Marian C; Schmidt, Tobias; Mitova, Tatyana; Fierstra, Jorn; Bellut, David; Regli, Luca; Burkhardt, Jan-Karl; Bozinov, Oliver

    2016-06-01

    The aim of this study is to analyze the association of preoperative usage of angiotensin converting enzyme (ACE) inhibitors with the initial presentation and clinical outcome of patients with chronic subdural hematoma (cSDH). Patients treated for cSDH between 2009 and 2013 at our institution were included in this retrospective case-control study. Medical charts were reviewed retrospectively and data were analyzed using descriptive and inferential statistics. Out of 203 patients (58 females, mean age 73.2years), 53 (26%) patients were on ACE inhibitors before their presentation with cSDH. Median initial hematoma volume in individuals with ACE inhibitors (179.2±standard error of the mean [SEM] 13.0ml) was significantly higher compared to patients without ACE inhibitors (140.4±SEM 6.2ml; p=0.007). There was an increased probability of surgical reintervention in the ACE inhibitor group (12/53, 23% versus 19/153, 12%; p=0.079), especially in patients older than 80years (6/23, 26% versus 3/45, 7%; p=0.026). ACE inhibitors are associated with higher hematoma volume in patients with cSDH and with a higher frequency of recurrences requiring surgery (especially in the very old). We hypothesize that these effects are due to ACE inhibitor induced bradykinin elevation causing increased vascular permeability of the highly vascularized neomembranes in cSDH. PMID:26898577

  19. Association of angiotensin-converting enzyme inhibitor therapy and comorbidity in diabetes: results from the Vermont diabetes information system

    MacLean Charles D

    2008-12-01

    Full Text Available Abstract Background Angiotensin converting enzyme inhibitors (ACE inhibitors reduce peripheral vascular resistance via blockage of angiotensin converting enzyme (ACE. ACE inhibitors are commonly used to treat congestive heart failure and high blood pressure, but other effects have been reported. In this study, we explored the association between ACE inhibitor therapy and the prevalence of comorbid conditions in adults with diabetes Methods We surveyed 1003 adults with diabetes randomly selected from community practices. Patients were interviewed at home and self-reported their personal and clinical characteristics including comorbidity. Current medications were obtained by direct observation of medication containers. We built logistic regression models with the history of comorbidities as the outcome variable and the current use of ACE inhibitors as the primary predictor variable. We adjusted for possible confounding by social (age, sex, alcohol drinking, cigarette smoking and clinical factors (systolic blood pressure, body mass index (BMI, glycosolated hemoglobin (A1C, number of comorbid conditions, and number of prescription medications. Results ACE users reported a history of any cancer (except the non-life-threatening skin cancers less frequently than non-users (10% vs. 15%; odd ratio = 0.59; 95% confidence interval [0.39, 0.89]; P = 0.01; and a history of stomach ulcers or peptic ulcer disease less frequently than non-users (12% vs. 16%, odd ratio = 0.70, [0.49, 1.01], P = 0.06. After correcting for potential confounders, ACE inhibitors remained significantly inversely associated with a personal history of cancer (odds ratio = 0.59, [0.39, 0.89]; P = 0.01 and peptic ulcer disease (odd ratio = 0.68, [0.46, 1.00], P = 0.05. Conclusion ACE inhibitor use is associated with a lower likelihood of a history of cancer and peptic ulcers in patients with diabetes. These findings are limited by the cross sectional study design, self-report of comorbid

  20. Reduction of exercise-induced myocardial ischemia during add-on treatment with the angiotensin-converting enzyme inhibitor enalapril in patients with normal left ventricular function and optimal beta blockade

    van den Heuvel, AFM; Dunselman, PHJM; Kingma, T; Verhorst, P; Boomsma, F; van Gilst, WH; van Veldhuisen, DJ

    2001-01-01

    OBJECTIVES We sought to study the effect of angiotensin-converting enzyme inhibition on exercise-induced myocardial ischemia. BACKGROUND Although angiotensin-converting enzyme inhibitors have been shown to reduce ischemic events after myocardial infarction, few data are available regarding their dir

  1. 2 year followup of patients with diabetes mellitus nephropathy showing albuminuria reversal following angiotensin converting enzyme inhibitors

    S Gopinath

    2012-01-01

    Full Text Available Introduction: Two-year follow-up of patients with diabetes mellitus (DM nephropathy shows albuminuria reversal following angiotensin converting enzyme (ACE inhibitors. Aim: To study about a clinical profile of 2-year follow-up of patients with DM nephropathy showing albuminuria reversal following ACE inhibitors. Materials and Methods: Twenty patients were taken up for study with duly informed consent and suggested for glycemic profile with HbA1C. Baseline renal function, urine microscopy, albuminuria, and other microvascular complications such as neuropathy and retinopathy. These patients were followed up for a period of 2 years with every month follow-up and monthly dose titration of ACE inhibitors, enalapril (Quote: Dr. M. K. Mani, to a maximum tolerable dose and checked after 1 week for raise in creatinine and potassium. Inclusion Criteria: Twenty patients, who have attended a secondary level diabetic clinic with diabetic nephropathy and are on regular follow-up for 2 years, were selected. Exclusion Criteria: Sick patients requiring parenteral feeds, IV antibiotics, co-morbid conditions such as autonomic gastroparesis and diabetic foot infections, type 1 diabetes and other known kidney disease, chronic kidney disease on dialysis are excluded from the study. Expected Result: Reversal of albuminuria. Conclusion: Enalapril is a safe, cheaper ACE inhibitors and the good dose titration coupled with early screening for DM nephropathy really help in halting the progression of chronic kidney disease from DM nephropathy.

  2. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial

    NN, NN; Yusuf, S; Teo, K;

    2008-01-01

    BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce major cardiovascular events, but are not tolerated by about 20% of patients. We therefore assessed whether the angiotensin-receptor blocker telmisartan would be effective in patients intolerant to ACE inhibitors with cardiovascular...... group). INTERPRETATION: Telmisartan was well tolerated in patients unable to tolerate ACE inhibitors. Although the drug had no significant effect on the primary outcome of this study, which included hospitalisations for heart failure, it modestly reduced the risk of the composite outcome...

  3. Clinical effects of early angiotensin-converting enzyme inhibitor treatment for acute myocardial infarction are similar in the presence and absence of aspirin: systematic overview of individual data from 96,712 randomized patients. Angiotensin-converting Enzyme Inhibitor Myocardial Infarction

    Latini, R; Tognoni, G; Maggioni, A P;

    2000-01-01

    OBJECTIVES: We sought to determine whether the clinical effects of early angiotensin-converting enzyme (ACE) inhibitor (ACEi) treatment for acute myocardial infarction (MI) are influenced by the concomitant use of aspirin (ASA). BACKGROUND: Aspirin and ACEi both reduce mortality when given early.......004). Angiotensin-converting enzyme inhibitor was associated with similar proportional reductions in 30-day mortality among the 86,484 patients who were taking ASA (6% [SD, 3%] reduction) and among the 10,228 patients who were not (10% [SD, 5%] reduction: chi-squared test of heterogeneity between these reductions...... = 0.4; p = 0.5). Angiotensin-converting enzyme inhibitor produced definite increases in the incidence of persistent hypotension (17.9% ACEi vs. 9.4% control) and of renal dysfunction (1.3% ACEi vs. 0.6% control), but there was no good evidence that these effects were different in the presence...

  4. The Use of Plasma-Derived Complement C1-Esterase Inhibitor Concentrate (Berinert®) in the Treatment of Angiotensin Converting Enzyme-Inhibitor Related Angioedema

    Hermanrud, Thorbjørn; Duus, Nicolaj; Bygum, Anette; Rasmussen, Eva Rye

    2016-01-01

    concentrate is a well-established treatment option of hereditary and acquired complement C1-esterase inhibitor deficiency, which are also mediated by an increased level of bradykinin resulting in recurrent angioedema. We here present a case of severe angiotensin converting enzyme-inhibitor related angioedema......Angioedema of the upper airways is a severe and potentially life-threatening condition. The incidence has been increasing in the past two decades, primarily due to pharmaceuticals influencing the generation or degradation of the vasoactive molecule bradykinin. Plasma-derived C1-esterase inhibitor...

  5. Angiotensin Converting Enzyme Activity in Alopecia Areata

    Mohammad Reza Namazi; Armaghan Ashraf; Farhad Handjani; Ebrahim Eftekhar; Amir Kalafi

    2014-01-01

    Background. Alopecia areata (AA) is a chronic inflammatory disease of the hair follicle. The exact pathogenesis of AA remains unknown, although recent studies support a T-cell mediated autoimmune process. On the other hand, some studies have proposed that the renin-angiotensin-aldosterone system (RAAS) may play a role in autoimmunity. Therefore, we assessed serum activity of angiotensin converting enzyme (ACE), a component of this system, in AA. Methods. ACE activity was measured in the sera ...

  6. Serum angiotensin converting enzyme in pneumonias.

    Kerttula, Y; Weber, T H

    1986-01-01

    Serum concentrations of angiotensin converting enzyme (ACE) were studied in pneumonias caused by different pathogens and in cases in which the aetiology could not be defined. In all aetiological groups, except in viral pneumonia, there was a significant increase in ACE during recovery (p less than 0.001). In several patients the lowest values during the acute phase of disease and the highest values during recovery were outside the reference limits. In cases with known aetiology the highest AC...

  7. A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group

    Køber, L; Torp-Pedersen, C; Carlsen, J E;

    1995-01-01

    BACKGROUND. Treatment with angiotensin-converting-enzyme (ACE) inhibitors reduces mortality among survivors of acute myocardial infarction, but whether to use ACE inhibitors in all patients or only in selected patients is uncertain. METHODS. We screened 6676 consecutive patients with 7001......, and the development of severe heart failure. That mortality was reduced in a randomized study enrolling 25 percent of consecutive patients screened should encourage the selective use of ACE inhibition after myocardial infarction....

  8. Sleep-related movement disorder symptoms in SHR are attenuated by physical exercise and an angiotensin-converting enzyme inhibitor.

    Frank, Miriam Kannebley; de Mello, Marco Tulio; Lee, Kil Sun; Daubian-Nosé, Paulo; Tufik, Sergio; Esteves, Andrea Maculano

    2016-02-01

    The relationship between hypertension and sleep-related movement disorders has been hypothesized for humans, but the causes and mechanisms have not been elucidated. We investigated whether an alteration in blood pressure (BP) induced by physical exercise and/or an angiotensin-converting enzyme inhibitor (enalapril) could affect locomotor activity in spontaneously hypertensive rats, with emphasis on the dopaminergic system. We used SHR and normotensive Wistar rats distributed into 4 groups for each strain: control, physical exercise, enalapril and physical exercise+enalapril. Physical exercise was performed on a treadmill, and enalapril was administered by gavage, both for 8weeks. During this period, locomotor activity was evaluated in an open field test, and BP was evaluated by tail plethysmography. Dopaminergic receptors, dopamine transporter and tyrosine hydroxylase levels at the striatum were evaluated by Western blotting. The control group of spontaneously hypertensive rats showed higher BP, increased activity in the open field test and lower levels of D2 receptors and tyrosine hydroxylase compared with all other groups throughout the experimental period. In general, physical exercise and enalapril attenuated these alterations. This study suggested the existence of comorbidity between hypertension and sleep-related movement disorders in spontaneously hypertensive rats. Physical exercise and enalapril conferred protection for both hypertension and the observed behavioral changes. In addition, these treatments led to changes in dopaminergic signaling in the striatal region (i.e., D2 receptor, TH and DAT). PMID:26650246

  9. A comparative study of neuroprotective effect of angiotensin converting enzyme inhibitors against scopolamine-induced memory impairments in rats

    Jawaid, Talha; Jahan, Shah; Kamal, Mehnaz

    2015-01-01

    The comparative study of neuroprotective effect of angiotensin converting enzyme inhibitors against scopolamine-induced neuroinflammation in albino Wistar rats was studied. Male albino rats were administered with scopolamine to induce memory impairment. The standard nootropic agent, piracetam (200 mg/kg b.w., [i.p.]), perindopril (0.1 mg/kg b.w., [i.p.]), enalapril (0.1 mg/kg b.w., [i.p.]), and ramipril (0.1 mg/kg b.w., [i.p.]) were administered in different group of animals for 5 days. On 5th day, scopolamine (1 mg/kg b.w., i.p.) was administered after 60 min of the last dose of test drug. Memory function was evaluated in Morris water maze (MWM) test and pole climbing test (PCT). Biochemical estimations like glutathione (GSH), malondialdehyde (MDA), and acetylcholinesterase activity in the brain were estimated after completion of behavior study. All three test groups shows improvement in learning and memory in comparison to control group. Perindopril treated group showed a more effective significant decrease in escape latency time and transfer latency time compared to enalapril and ramipril treated group on day 4 in MWM test and PCT, respectively. Perindopril shows a significant reduction in MDA level and acetylcholinesterase activity and a significant rise in GSH level compared to enalapril and ramipril. The finding of this study indicates that Perindopril is more effective in memory retention compared to enalapril and ramipril. PMID:26317078

  10. A comparative study of neuroprotective effect of angiotensin converting enzyme inhibitors against scopolamine-induced memory impairments in rats

    Talha Jawaid

    2015-01-01

    Full Text Available The comparative study of neuroprotective effect of angiotensin converting enzyme inhibitors against scopolamine-induced neuroinflammation in albino Wistar rats was studied. Male albino rats were administered with scopolamine to induce memory impairment. The standard nootropic agent, piracetam (200 mg/kg b.w., [i.p.], perindopril (0.1 mg/kg b.w., [i.p.], enalapril (0.1 mg/kg b.w., [i.p.], and ramipril (0.1 mg/kg b.w., [i.p.] were administered in different group of animals for 5 days. On 5 th day, scopolamine (1 mg/kg b.w., i.p. was administered after 60 min of the last dose of test drug. Memory function was evaluated in Morris water maze (MWM test and pole climbing test (PCT. Biochemical estimations like glutathione (GSH, malondialdehyde (MDA, and acetylcholinesterase activity in the brain were estimated after completion of behavior study. All three test groups shows improvement in learning and memory in comparison to control group. Perindopril treated group showed a more effective significant decrease in escape latency time and transfer latency time compared to enalapril and ramipril treated group on day 4 in MWM test and PCT, respectively. Perindopril shows a significant reduction in MDA level and acetylcholinesterase activity and a significant rise in GSH level compared to enalapril and ramipril. The finding of this study indicates that Perindopril is more effective in memory retention compared to enalapril and ramipril.

  11. A comparative study of neuroprotective effect of angiotensin converting enzyme inhibitors against scopolamine-induced memory impairments in rats.

    Jawaid, Talha; Jahan, Shah; Kamal, Mehnaz

    2015-01-01

    The comparative study of neuroprotective effect of angiotensin converting enzyme inhibitors against scopolamine-induced neuroinflammation in albino Wistar rats was studied. Male albino rats were administered with scopolamine to induce memory impairment. The standard nootropic agent, piracetam (200 mg/kg b.w., [i.p.]), perindopril (0.1 mg/kg b.w., [i.p.]), enalapril (0.1 mg/kg b.w., [i.p.]), and ramipril (0.1 mg/kg b.w., [i.p.]) were administered in different group of animals for 5 days. On 5(th) day, scopolamine (1 mg/kg b.w., i.p.) was administered after 60 min of the last dose of test drug. Memory function was evaluated in Morris water maze (MWM) test and pole climbing test (PCT). Biochemical estimations like glutathione (GSH), malondialdehyde (MDA), and acetylcholinesterase activity in the brain were estimated after completion of behavior study. All three test groups shows improvement in learning and memory in comparison to control group. Perindopril treated group showed a more effective significant decrease in escape latency time and transfer latency time compared to enalapril and ramipril treated group on day 4 in MWM test and PCT, respectively. Perindopril shows a significant reduction in MDA level and acetylcholinesterase activity and a significant rise in GSH level compared to enalapril and ramipril. The finding of this study indicates that Perindopril is more effective in memory retention compared to enalapril and ramipril. PMID:26317078

  12. Cardiovascular risk reduction in hypertension: angiotensin-converting enzyme inhibitors, angiotensin receptor blockers. Where are we up to?

    Sindone, A; Erlich, J; Lee, C; Newman, H; Suranyi, M; Roger, S D

    2016-03-01

    Previously, management of hypertension has concentrated on lowering elevated blood pressure. However, the target has shifted to reducing absolute cardiovascular (CV) risk. It is estimated that two in three Australian adults have three or more CV risk factors at the same time. Moderate reductions in several risk factors can, therefore, be more effective than major reductions in one. When managing hypertension, therapy should be focused on medications with the strongest evidence for CV event reduction, substituting alternatives only when a primary choice is not appropriate. Hypertension management guidelines categorise angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) interchangeably as first-line treatments in uncomplicated hypertension. These medications have different mechanisms of action and quite different evidence bases. They are not interchangeable and their prescription should be based on clinical evidence. Despite this, currently ARB prescriptions are increasing at a higher rate than those for ACEI and other antihypertensive classes. Evidence that ACEI therapy prevents CV events and death, in patients with coronary artery disease or multiple CV risk factors, emerged from the European trial on reduction of cardiac events with perindopril in stable coronary artery disease (EUROPA) and Heart Outcomes Prevention Evaluation (HOPE) trials respectively. The consistent benefit has been demonstrated in meta-analyses. The clinical trial data for ARB are less consistent, particularly regarding CV outcomes and mortality benefit. The evidence supports the use of ACEI (Class 1a) compared with ARB despite current prescribing trends. PMID:26968600

  13. Combined treatment of vitamin K2 and angiotensin-converting enzyme inhibitor ameliorates hepatic dysplastic nodule in a patient with liver cirrhosis

    Yoshiji, Hitoshi; NOGUCHI, RYUICHI; Yamazaki, Masaharu; IKENAKA, YASUHIDE; SAWAI, MASAYOSHI; Ishikawa, Masatoshi; Kawaratani, Hideto; MASHITANI, TSUYOSHI; Kitade, Mitsuteru; Kaji, Kosuke; Uemura, Masahito; YAMAO, JUNICHI; Fujimoto, Masao; Mitoro, Akira; Toyohara, Masahisa

    2007-01-01

    Although it is well known that the hepatocellular carcinoma (HCC) is an ominous complication in patients with liver cirrhosis, there has been no approved drug to prevent the development of HCC to date. We previously reported that the combined treatment of vitamin K2 (VK) and angiotensin-converting enzyme inhibitor (ACE-I) significantly suppressed the experimental hepatocarcinogenesis. A 66-year-old Japanese woman with hepatitis C virus (HCV)-related liver cirrhosis developed a dysplastic nodu...

  14. Radiation-induced endothelial dysfunction and fibrosis in rat lung: modification by the angiotensin converting enzyme inhibitor CL242817

    The purpose of this study was to evaluate the angiotensin converting enzyme (ACE) inhibitor CL242817 as a modifier of radiation-induced pulmonary endothelial dysfunction and pulmonary fibrosis in rats sacrificed 2 months after a single dose of 60Co gamma rays (0-30 Gy) to the right hemithorax. CL242817 was administered in the feed continuously after irradiation at a regimen of 60 mg/kg/day. Pulmonary endothelial function was monitored by lung ACE activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Pulmonary fibrosis was evaluated by lung hydroxyproline (HP) content. Lung ACE and PLA activities decreased with increasing radiation dose, and cotreatment with CL242817 significantly ameliorated both responses. CL242817 dose-reduction factors (DRF) were 1.3-1.5 for ACE and PLA activity. Lung PGI2 and TXA2 production increased with increasing radiation dose, and CL242817 almost completely prevented both radiation responses. The slope of the radiation dose-response curves in the CL242817-treated rats was essentially zero, precluding calculation of DRF values for PGI2 and TXA2 production. Lung HP content also increased with increasing radiation dose, and CL242817 significantly attenuated this response (DRF = 1.5). These data suggest that the ability of ACE inhibitors to ameliorate radiation-induced pulmonary endothelial dysfunction is not unique to captopril, rather it is a therapeutic action shared by other members of this class of compounds. These data also provide the first evidence that ACE inhibitors exhibit antifibrotic activity in irradiated rat lung

  15. Synthesis of angiotensin-converting enzyme (ACE inhibitors: an important class of antihypertensive drugs

    Lima Dênis Pires de

    1999-01-01

    Full Text Available This report outlines the discovery, the design and development of new compounds, and, structure-activity relationships for this drug category. Updated approaches to planned syntheses of new worthy ACE-inhibitors are also exploited.

  16. Different angiotensin-converting enzyme inhibitors have similar clinical efficacy after myocardial infarction

    Hansen, Morten L; Gislason, Gunnar H; Køber, Lars;

    2008-01-01

    efficacy. Risk of all-cause mortality: trandolapril (reference) 1.00, ramipril 0.97 (0.89, 1.05), enalapril 1.04 (0.95, 1.150), captopril 0.95 (0.83, 1.08), perindopril 0.98 (0.84, 1.15) and other ACE inhibitors or angiotensin II receptor blockers (ARB) 1.06 (0.94, 1.19). Reinfarction: trandolapril...... (reference) 1.00, ramipril 0.98 (0.89, 1.08), enalapril 1.04 (0.92, 1.17), captopril 1.05 (0.89, 1.25), perindopril 0.96 (0.81, 1.14) and other ACE inhibitors or ARB 0.99 (0.86, 1.14). Furthermore, the association between ARBs and clinical events was similar to ACE inhibitors (trandolapril reference): all...

  17. Decreased Risk of Radiation Pneumonitis With Incidental Concurrent Use of Angiotensin-Converting Enzyme Inhibitors and Thoracic Radiation Therapy

    Kharofa, Jordan [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Cohen, Eric P. [Department of Medicine, Division of Nephrology, Medical College of Wisconsin, Milwaukee, WI (United States); Tomic, Rade [Department of Medicine, Division of Pulmonology, Medical College of Wisconsin, Milwaukee, WI (United States); Xiang Qun [Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI (United States); Gore, Elizabeth, E-mail: Egore@mcw.edu [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States)

    2012-09-01

    Purpose: Angiotensin-converting enzyme (ACE) inhibitors have been shown to mitigate radiation-induced lung injury in preclinical models. The aim of this study was to evaluate whether ACE inhibitors decrease the risk of radiation pneumonitis in lung cancer patients receiving thoracic irradiation. Methods and Materials: Patients with Stage I through III small-cell and non-small-cell lung cancer treated definitively with radiation from 2004-2009 at the Clement J. Zablocki Veterans Affairs Medical Center were retrospectively reviewed. Acute pulmonary toxicity was quantified within 6 months of completion of treatment according to the Common Terminology Criteria for Adverse Events version 4. The use of ACE inhibitors, nonsteroidal anti-inflammatory drugs, inhaled glucocorticosteroids, statins, and angiotensin receptor blockers; dose-volume histogram parameters; and patient factors were assessed for association with Grade 2 or higher pneumonitis. Results: A total of 162 patients met the criteria for inclusion. The majority of patients had Stage III disease (64%) and received concurrent chemotherapy (61%). Sixty-two patients were identified as ACE inhibitor users (38%). All patients had acceptable radiation plans based on dose-volume histogram constraints (V20 [volume of lung receiving at least 20 Gy] {<=}37% and mean lung dose {<=}20 Gy) with the exception of 2 patients who did not meet both criteria. Grade 2 or higher pulmonary toxicity occurred in 12 patients (7.4%). The rate of Grade 2 or higher pneumonitis was lower in ACE inhibitor users vs. nonusers (2% vs. 11%, p = 0.032). Rates of Grade 2 or higher pneumonitis were significantly increased in patients aged greater than 70 years (16% vs. 2%, p = 0.005) or in whom V5 (volume of lung receiving at least 5 Gy) was 50% or greater (13% vs. 4%, p = 0.04). V10 (volume of lung receiving at least 10 Gy), V20, V30 (volume of lung receiving at least 30 Gy), and mean lung dose were not independently associated with Grade 2 or

  18. Angiotensin-Receptor Blocker, Angiotensin-Converting Enzyme Inhibitor, and Risks of Atrial Fibrillation: A Nationwide Cohort Study.

    Hsieh, Yu-Cheng; Hung, Chen-Ying; Li, Cheng-Hung; Liao, Ying-Chieh; Huang, Jin-Long; Lin, Ching-Heng; Wu, Tsu-Juey

    2016-05-01

    Both angiotensin-receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI) have protective effects against atrial fibrillation (AF). The differences between ARB and ACEI in their effects on the primary prevention of AF remain unclear. This study compared ARB and ACEI in combined antihypertensive medications for reducing the risk of AF in patients with hypertension, and determined which was better for AF prevention in a nationwide cohort study.Patients aged ≥55 years and with a history of hypertension were identified from Taiwan National Health Insurance Research Database. Medical records of 25,075 patients were obtained, and included 6205 who used ARB, 8034 who used ACEI, and 10,836 nonusers (no ARB or ACEI) in their antihypertensive regimen. Cox regression models were applied to estimate the hazard ratio (HR) for new-onset AF.During an average of 7.7 years' follow-up, 1619 patients developed new-onset AF. Both ARB (adjusted HR: 0.51, 95% CI 0.44-0.58, P reduced the risk of AF compared to nonusers. Subgroup analysis showed that ARB and ACEI were equally effective in preventing new-onset AF regardless of age, gender, the presence of heart failure, diabetes, and vascular disease, except for those with prior stroke or transient ischemic attack (TIA). ARB prevents new-onset AF better than ACEI in patients with a history of stroke or TIA (log-rank P = 0.012).Both ARB and ACEI reduce new-onset AF in patients with hypertension. ARB prevents AF better than ACEI in patients with a history of prior stroke or TIA. PMID:27196491

  19. Association of plasminogen activator inhibitor-1 and angiotensin converting enzyme polymorphisms with recurrent pregnancy loss in Iranian women

    Fatemeh Shakarami

    2015-10-01

    Full Text Available Background: Recurrent pregnancy loss (RPL defined by two or more failed pregnancies before 20 weeks of gestation. Several factors play a role in RPL including thrombophilic conditions which can be influenced by gene polymorphisms. Plasminogen activator inhibitor-1 (PAI-1 and angiotensin converting enzyme (ACE genes are closely related to fibrinolytic process, embryonic development and pregnancy success. Objective: The aim of this study was to investigate the relationship between RPL and common polymorphisms in ACE and PAI-1 genes. Materials and Methods: In this case control study, 100 women with recurrent abortions (at least two were selected as cases and 100 healthy women with two or more normal term deliveries without a history of abortion as controls. Total genomic DNA was isolated from blood leukocytes. The status of the PAI-1 4G/5G and ACE (D/I polymorphism was determined by PCR-RFLP. Results: Homozygosity for PAI-1 4G polymorphism was seen in 17 cases (17%, and 5 controls (5% (p=0.006 so patients with homozygote 4G mutation were significantly more prone to RPL in contrast to control group (OR: 4.63, % 95 CI: 1.55-13.84. In addition, 7 patients (7 %, and no one from the control group, were homozygote (I/I for ACE polymorphism (p=0.034, suggesting no significant associations between ACE D allele or DD genotype and RPL. Conclusion: Considering these results, because 4G/4G polymorphism for PAI-1 gene could be a thrombophilic variant leading to abortion, analysis of this mutation and other susceptibility factors are recommended in patients with RPL.

  20. Changes of Plasma Angiotensin-Converting Enzyme Activity during Hemodialysis *

    Koo, Wan Suh; Lee, Yong Joon; Kim, Hye Su; Kim, Suk Young; Choi, Euy Jin; Chang, Yoon Sik; Yoon, Young Suk; Bang, Byung Kee

    1987-01-01

    Plasma angiotensin-converting enzyme activity was measured by spectrophotometer in normal subjects and in patients with end stage renal failure, serially during a routine hemodialysis. Patients on maintenance hemodialysis tended to be associated with elevated plasma angiotensin-converting enzyme activity versus normal subjects. Plasma angiotensin-converting enzyme activity was significantly elevated in patients with chronic renal failure after 5 hours of hemodialysis(p

  1. The binding of metal ions and angiotensin converting enzyme (ACE) inhibitor by 13C NMR

    Sakamoto, Yohko; Sakamoto, Yuko; Ishii, Tomoko; Ohmoto, Taichi

    1991-06-01

    Enalaprilat (MK-422, 1- [ N- [1 (S)-carboxy-3-phenylpropyl]- L-alanyl]- L-proline (1)) and Lisinopril (MK521, N- N- [ (s)-l-carboxy-3- phenylpropyl]- L-lysyl- L-proline, (2)) exhibit the capacity to act as a chelate, unidentate or bridge towards metal ions in aqueous solution, as determined by 13C NMR. By adding metal ions, in the series of Zn 2+, Ni 2+, Pb 2+, Pd 2+ and Cd 2+, the active site of the ACE inhibitor was well defined. MK-521 was more influenced by nuclei that were distant from the active site than MK-422.

  2. The Use of Plasma-Derived Complement C1-Esterase Inhibitor Concentrate (Berinert®) in the Treatment of Angiotensin Converting Enzyme-Inhibitor Related Angioedema.

    Hermanrud, Thorbjørn; Duus, Nicolaj; Bygum, Anette; Rasmussen, Eva Rye

    2016-01-01

    Angioedema of the upper airways is a severe and potentially life-threatening condition. The incidence has been increasing in the past two decades, primarily due to pharmaceuticals influencing the generation or degradation of the vasoactive molecule bradykinin. Plasma-derived C1-esterase inhibitor concentrate is a well-established treatment option of hereditary and acquired complement C1-esterase inhibitor deficiency, which are also mediated by an increased level of bradykinin resulting in recurrent angioedema. We here present a case of severe angiotensin converting enzyme-inhibitor related angioedema (ACEi-AE) of the hypopharynx that completely resolved rapidly after the infusion of plasma-derived C1-inhibitor concentrate adding to the sparse reports in the existing literature. PMID:27123347

  3. The Use of Plasma-Derived Complement C1-Esterase Inhibitor Concentrate (Berinert®) in the Treatment of Angiotensin Converting Enzyme-Inhibitor Related Angioedema

    Hermanrud, Thorbjørn; Duus, Nicolaj; Bygum, Anette; Rasmussen, Eva Rye

    2016-01-01

    Angioedema of the upper airways is a severe and potentially life-threatening condition. The incidence has been increasing in the past two decades, primarily due to pharmaceuticals influencing the generation or degradation of the vasoactive molecule bradykinin. Plasma-derived C1-esterase inhibitor concentrate is a well-established treatment option of hereditary and acquired complement C1-esterase inhibitor deficiency, which are also mediated by an increased level of bradykinin resulting in recurrent angioedema. We here present a case of severe angiotensin converting enzyme-inhibitor related angioedema (ACEi-AE) of the hypopharynx that completely resolved rapidly after the infusion of plasma-derived C1-inhibitor concentrate adding to the sparse reports in the existing literature. PMID:27123347

  4. The angiotensin converting enzyme inhibitor trandolapril has neutral effect on exercise tolerance or functional class in patients with myocardial infarction and reduced left ventricular systolic function

    Abdulla, Jawdat; Burchardt, Hans; Z Abildstrøm, Steen;

    2003-01-01

    AIMS: To study the effect of angiotensin-converting enzyme (ACE) inhibitor trandolapril on exercise tolerance time (ETT) and New York Heart Association (NYHA) classification in patients with reduced left ventricular systolic dysfunction (LVSD) after acute myocardial infarction (AMI). METHODS....../day of furosemide was spared in trandolapril arm (P=0.001). CONCLUSIONS: Trandolapril had a mild diuretic-sparing effect. These results emphasis the importance of explaining to patients that ACE inhibitors provide protection against death and hospitalisation for heart failure but do not have any significant effect...

  5. Severe hepatic encephalopathy in a patient with liver cirrhosis after administration of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker combination therapy: a case report

    Podda Mauro

    2010-05-01

    Full Text Available Abstract Introduction A combination therapy of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers has been used to control proteinuria, following initial demonstration of its efficacy. However, recently concerns about the safety of this therapy have emerged, prompting several authors to urge for caution in its use. In the following case report, we describe the occurrence of a serious and unexpected adverse drug reaction after administration of a combination of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers to a patient with nephrotic syndrome and liver cirrhosis with severe portal hypertension. Case presentation We administered this combination therapy to a 40-year-old Caucasian man with liver cirrhosis in our Hepatology Clinic, given the concomitant presence of glomerulopathy associated with severe proteinuria. While the administration of one single drug appeared to be well-tolerated, our patient developed severe acute encephalopathy after the addition of the second one. Discontinuation of the therapy led to the disappearance of the side-effect. A tentative rechallenge with the same drug combination led to a second episode of acute severe encephalopathy. Conclusion We speculate that this adverse reaction may be directly related to the effect of angiotensin II on the excretion of blood ammonia. Therefore, we suggest that patients with liver cirrhosis and portal hypertension are at risk of developing clinically relevant encephalopathy when angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker combination therapy is administered, thus indicating the need for a careful clinical follow-up. In addition, the incidence of this serious side-effect should be rigorously evaluated in all patients with liver cirrhosis administered with this common treatment combination.

  6. Anti-atherosclerotic effects of an angiotensin converting enzyme inhibitor and an angiotensin II antagonist in Cynomolgus monkeys fed a high-cholesterol diet

    Miyazaki, Mizuo; Sakonjo, Hiroshi; Takai, Shinji

    1999-01-01

    We investigated the relationship between angiotensin II formation and the development of atherosclerotic lesions in the aorta of monkeys (Macaca fascicularis) fed a high-cholesterol (4% cholesterol and 6% corn oil) diet for 6 months, and studied the effects of an angiotensin converting enzyme (ACE) inhibitor, trandolapril (10 mg kg−1 per day, p.o.), and an angiotensin II type 1 receptor antagonist, 2-butyl-4-(methylthio)-1-[[2′[[[(propylamino)carbonyl]amino]sulfonyl](1,1′-biphenyl)-4-yl]methy...

  7. Calcitriol regulates angiotensin-converting enzyme and angiotensin converting-enzyme 2 in diabetic kidney disease.

    Lin, Mei; Gao, Ping; Zhao, Tianya; He, Lei; Li, Mengshi; Li, Yaoyao; Shui, Hua; Wu, Xiaoyan

    2016-05-01

    To investigate the effects of calcitriol on angiotensin-converting enzyme (ACE) and ACE2 in diabetic nephropathy. Streptozotocin (STZ) induced diabetic rats were treated with calcitriol for 16 weeks. ACE/ACE2 and mitogen activated protein kinase (MAPK) enzymes were measured in the kidneys of diabetic rats and rat renal tubular epithelial cells exposed to high glucose. Calcitriol reduced proteinuria in diabetic rats without affecting calcium-phosphorus metabolism. ACE and ACE2 levels were significantly elevated in diabetic rats compared to those in control rats. The increase in ACE levels was greater than that of ACE2, leading to an elevated ACE/ACE2 ratio. Calcitriol reduced ACE levels and ACE/ACE2 ratio and increased ACE2 levels in diabetic rats. Similarly, high glucose up-regulated ACE expression in NRK-52E cells, which was blocked by the p38 MAPK inhibitor SB203580, but not the extracellular signal-regulated kinase (ERK) inhibitor FR180204 or the c-Jun N-terminal kinase (JNK) inhibitor SP600125. High glucose down-regulated ACE2 expression, which was blocked by FR180204, but not SB203580 or SP600125. Incubation of cells with calcitriol significantly inhibited p38 MAPK and ERK phosphorylation, but not JNK phosphorylation, and effectively attenuated ACE up-regulation and ACE2 down-regulation in high glucose conditions. The renoprotective effects of calcitriol in diabetic nephropathy were related to the regulation of tubular levels of ACE and ACE2, possibly by p38 MAPK or ERK, but not JNK pathways. PMID:26968558

  8. Nationwide trends in the prescription of beta-blockers and angiotensin-converting enzyme inhibitors after myocardial infarction in Denmark, 1995-2002

    Gislason, Gunnar H; Abildstrom, Steen Z; Rasmussen, Jeppe Nørgaard;

    2005-01-01

    OBJECTIVES: To study the use of beta-blockers and angiotensin-converting enzyme (ACE) inhibitors after acute myocardial infarction (AMI) in Denmark from 1995 to 2002. DESIGN: Information about patients with first AMI aged > or = 30 years and the dispensing of beta-blockers and ACE inhibitors from......-diuretics and antidiabetic drugs received beta-blockers less frequently, but patients taking loop-diuretics or antidiabetic drugs had the greatest increase. ACE inhibitor use increased from 24.5 to 35.5% (OR = 1.86, CI: 1.72-2.01). Women, patients aged or = 80 years and patients not taking loop......-diuretics received ACE inhibitors less frequently, but patients not taking loop-diuretics had the greatest increase. CONCLUSIONS: Beta-blocker use increased markedly post-AMI from 1995 to 2002, whereas ACE inhibitor use increased modestly. The results suggested undertreatment of women, elderly patients and people...

  9. Effects of long-term treatment with angiotensin-converting-enzyme inhibitors in the presence or absence of aspirin: a systematic review

    Teo, Koon K; Yusuf, Salim; Pfeffer, Marc;

    2002-01-01

    BACKGROUND: Results from a retrospective analysis of the Studies of Left Ventricular Dysfunction (SOLVD) study suggest that angiotensin-converting-enzyme (ACE) inhibitors may be less effective in patients receiving aspirin. We aimed to confirm or refute this theory. METHODS: We used the Peto......-Yusuf method to undertake a systematic overview of data for 22060 patients from six long-term randomised trials of ACE inhibitors to assess whether aspirin altered the effects of ACE inhibitor therapy on major clinical outcomes (composite of death, myocardial infarction, stroke, hospital admission...... between the proportional reductions in risk with ACE inhibitor therapy in the presence or absence of aspirin for the major clinical outcomes (p=0.15), or in any of its individual components, except myocardial infarction (interaction p=0.01). Overall, ACE inhibitor therapy significantly reduced the risk...

  10. Angiotensin Converting Enzyme-induced Angioedema - A Dangerous New Epidemic

    Rasmussen, Eva Rye; Mey, Kristianna; Bygum, Anette

    2013-01-01

    Angioedema is a sudden localised and often asymmetric swelling of the skin or mucous membranes caused by transient increased endothelial permeability causing plasma extravasation. In the last decades the incidence of severe angioedema involving the upper airways and even fatal outcome due to...... asphyxia has increased. This is mainly due to pharmaceuticals such as angiotensin converting enzyme-inhibitors, which are extensively used worldwide. Some aspects of the pathophysiology have been elucidated and the vasoactive molecule bradykinin is shown to be one of the main causative agents. The...

  11. How should we manage heart failure developing in patients already treated with angiotensin-converting enzyme inhibitors and beta-blockers for hypertension, diabetes or coronary disease?

    Gustafsson, Finn; Segura, Julian; Ruilope, Luis M

    2010-01-01

    An increasing number of patients in the community are being treated with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and beta-blockers for hypertension, coronary disease or diabetic renal and vascular complications. Some of these patients will develop heart...... failure despite such treatment. Based on data from hypertension trials it can be estimated that approximately 5% of treated patients will develop heart failure over 5 years. It is unclear whether patients developing heart failure on and off ACE-inhibitors or beta-blockers, respectively, at the time of...... heart failure diagnosis have similar prognosis.Treatment options for patients developing heart failure while already treated with ACE inhibitors/ARBs and beta-blockers are very limited if current heart failure guidelines are followed. In this review possible strategies are outlined and important areas...

  12. How should we manage heart failure developing in patients already treated with angiotensin-converting enzyme inhibitors and beta-blockers for hypertension, diabetes or coronary disease?

    Gustafsson, Finn; Segura, Julian; Ruilope, Luis M

    2010-01-01

    An increasing number of patients in the community are being treated with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and beta-blockers for hypertension, coronary disease or diabetic renal and vascular complications. Some of these patients will develop heart...... failure despite such treatment. Based on data from hypertension trials it can be estimated that approximately 5% of treated patients will develop heart failure over 5 years. It is unclear whether patients developing heart failure on and off ACE-inhibitors or beta-blockers, respectively, at the time...... of heart failure diagnosis have similar prognosis.Treatment options for patients developing heart failure while already treated with ACE inhibitors/ARBs and beta-blockers are very limited if current heart failure guidelines are followed. In this review possible strategies are outlined and important areas...

  13. A meta-analysis of the effect of angiotensin-converting enzyme inhibitors on functional capacity in patients with symptomatic left ventricular systolic dysfunction

    Abdulla, Jawdat; Abildstrøm, Steen Zabell; Køber, Lars Valeur;

    2004-01-01

    AIM: To determine by meta-analysis whether angiotensin-converting enzyme (ACE) inhibitors improve exercise tolerance in patients with symptomatic left ventricular systolic dysfunction (LVSD). METHODS AND RESULTS: After literature search 13 multi-centre double blind parallel group trials...... that evaluated the effect of ACE inhibitors vs. placebo on exercise duration were selected. Ninety-four percent of patients were in New York Heart Association class II-IV. The studies were combined using the Cochrane meta-analysis program (Review manager version 4.1). Analyses according to treatment period......, exercise protocols and publication periods were performed. Treatment with ACE inhibitor over 4-12 weeks resulted in a beneficial effect on exercise duration (P=0.003 and P=0.0008 for 4- and 12-weeks treatment, respectively), but the magnitude of improvements did not exceed 30 s corresponding to only 5...

  14. Structure-function analysis of angiotensin-converting enzyme inhibitors as modifiers of radiation-induced pulmonary endothelial dysfunction in rats

    It was concluded that the angiotensin-converting enzyme (ACE) inhibitor CGS13945 modifies radiation-induced pulmonary endothelial dysfunction in rats, indicating that presence of a thiol group is not essential for therapeutic efficacy in this class of compounds. On the other hand, CGS13945 exhibits a differential sparing of radiation-induced pulmonary endothelial dysfunction, as does penicillamine. A structure-function analysis of the present and previous data indicates all of the ACE inhibitors tested (Captopril, CL242817 and CGS13945) spare the radiation-induced suppression in lung ACE and PLA activity; all of the thiol compounds tested (penicillamine, Captopril and CL242817) spare the radiation-induced elevation in lung PGI2 and TXA2 production; and the thiol ACE inhibitors (Captopril and CL242817) spare all four endothelial responses. (author)

  15. Effects of prednisolone on angiotensin converting enzyme activity.

    Roulston, J. E.; O'Malley, G I; Douglas, J G

    1984-01-01

    Plasma angiotensin converting enzyme was measured in 23 asthmatic subjects before and after administration of prednisolone, 20 mg daily, for seven days. Plasma specimens from seven patients with asthma, seven with sarcoidosis and 14 normal subjects were also assayed before and after the addition of prednisolone in vitro. A plasma free extract of normal lung was also prepared and assayed before and after prednisolone treatment. Mean angiotensin converting enzyme activity was significantly grea...

  16. Angiotensin-Converting Enzyme Inhibitor Use and Major Cardiovascular Outcomes in Type 2 Diabetes Mellitus Treated With the Dipeptidyl Peptidase 4 Inhibitor Alogliptin.

    White, William B; Wilson, Craig A; Bakris, George L; Bergenstal, Richard M; Cannon, Christopher P; Cushman, William C; Heller, Simon K; Mehta, Cyrus R; Nissen, Steven E; Zannad, Faiez; Kupfer, Stuart

    2016-09-01

    Activation of the sympathetic nervous system when there is dipeptidyl peptidase 4 inhibition in the presence of high-dose angiotensin-converting enzyme (ACE) inhibition has led to concerns of potential increases in cardiovascular events when the 2 classes of drugs are coadministered. We evaluated cardiovascular outcomes from the EXAMINE (Examination of Cardiovascular Outcomes With Alogliptin versus Standard of Care) trial according to ACE inhibitor use. Patients with type 2 diabetes mellitus and a recent acute coronary syndrome were randomly assigned to receive the dipeptidyl peptidase 4 inhibitor alogliptin or placebo added to existing antihyperglycemic and cardiovascular prophylactic therapies. Risks of adjudicated cardiovascular death, nonfatal myocardial infarction and stroke, and hospitalized heart failure were analyzed using a Cox proportional hazards model in patients according to ACE inhibitor use and dose. There were 3323 (62%) EXAMINE patients treated with an ACE inhibitor (1681 on alogliptin and 1642 on placebo). The composite rates of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke were comparable for alogliptin and placebo with ACE inhibitor (11.4% versus 11.8%; hazard ratio, 0.97; 95% confidence interval, 0.79-1.19; P=0.76) and without ACE inhibitor use (11.2% versus 11.9%; hazard ratio, 0.94; 95% confidence interval, 0.73-1.21; P=0.62). Composite rates for cardiovascular death and heart failure in patients on ACE inhibitor occurred in 6.8% of patients on alogliptin versus 7.2% on placebo (hazard ratio, 0.93; 95% confidence interval, 0.72-1.2; P=0.57). There were no differences for these end points nor for blood pressure or heart rate in patients on higher doses of ACE inhibitor. Cardiovascular outcomes were similar for alogliptin and placebo in patients with type 2 diabetes mellitus and coronary disease treated with ACE inhibitors. PMID:27480840

  17. REDUCTION OF CUMULATIVE CARDIOVASCULAR RISK IN PATIENTS WITH ARTERIAL HYPERTENSION: THE ROLE OF ANGIOTENSIN CONVERTING ENZYME INHIBITORS ACCORDING TO THE NEW EUROPEAN RECOMMENDATIONS

    M. N. Mamedov

    2007-01-01

    Full Text Available Conception of total cardio-vascular risk plays important role in defining tactics of arterial hypertension therapy according to the new European recommendations. Choice of antihypertensive therapy is based on meta-analysis of large clinical studies with hard end points. It is recommended to use five classes of antihypertensive drugs in mono- and combined therapy. Angiotensin converting enzyme (ACE inhibitors keep important place in the therapy of arterial hypertension accompanying with risk factors and associated diseases. Enalapril is one of the widely used ACE inhibitors, its efficiency was proved in prospective clinical studies. In high risk patients monotherapy with Enam (enalapril, Dr. Reddy’s decreases blood pressure and leads to positive metabolic changes. This results in significant risk reduction of cardio-vascular complications.

  18. The long-term impact of the angiotensin-converting enzyme inhibitor trandolapril on mortality and hospital admissions in patients with left ventricular dysfunction after a myocardial infarction: follow-up to 12 years

    Buch, Pernille; Rasmussen, Søren; Abildstrøm, Steen Zabell;

    2004-01-01

    AIMS: To investigate the long-term benefits of treatment with angiotensin-converting enzyme (ACE)-inhibitors in patients with myocardial infarction (MI) and left ventricular dysfunction (LVD). METHODS AND RESULTS: In the trandolapril cardiac evaluation (TRACE) study, 1749 patients with LVD...... (ejection fractionACE-inhibitor use. National registries were used to track...

  19. Angiotensin converting enzyme genotype in cardiovascular disease

    Summers, K.M.; Huggard, P.R.; West, M.J. [Univ. of Queensland, Brisbane (Australia)] [and others

    1994-09-01

    Angiotensin converting enzyme (ACE) catalyses formation of angiotensin II and degradation of bradykinin, vasoactive peptides with opposing properties. The result of ACE action is to promote vasoconstriction and cell growth. PCR is used to detect a common polymorphism due to the insertion of an Alu repeat element of 287 bp into intron 16. ACE genotype has been implicated in risk for myocardial infarction (MI) and hypertension in humans. We have studied a group of 640 patients (61% male aged 64 {plus_minus} 11 years) with myocardial ischaemic syndromes, followed for 12 months after initial hospital admission. In this group, the frequency of the insertion (I) allele was 0.47 (N=1170 chromosomes), not significantly higher than the frequency of 0.46 in 112 local blood donors (50% male aged 59 {plus_minus}5 years). In the 300 patients with diagnosed MI, I allele frequency was 0.48. This is significantly higher ({chi}{sup 2}=5.78, P=0.015) than the frequency of 0.42 reported in a multi-centre study of ACE genotype in 600 male European patients with MI . There was a non-significant increase in the frequency of a cardiac event within 6 months of hospital admission in those of II genotype (N=464, 47 events to date). These results suggest that in our population, the I allele and/or II genotype may be associated with risk of MI. This contrasts with the study cited above, where the D (deletion) allele and DD genotype frequency were raised in patients compared with controls. Hypertension is associated with the ACE D allele, and does not explain the heart disease risk, which may be associated with the I allele, in this group of survivors of myocardial ischaemic disease. The difference between our results and the previous study may be due to ascertainment or ethnic differences or to problems amplifying the I allele in some heterozygotes. Clearly, the role of ACE genotype in these diseases is complex.

  20. Effect of the angiotensin-converting enzyme inhibitor trandolapril on mortality and morbidity in diabetic patients with left ventricular dysfunction after acute myocardial infarction. Trace Study Group

    Gustafsson, I; Torp-Pedersen, C; Køber, L;

    1999-01-01

    OBJECTIVES: This study evaluated the efficacy of long-term treatment with the angiotensin-converting enzyme (ACE) inhibitor trandolapril in diabetic patients with left ventricular dysfunction after acute myocardial infarction (AMI). BACKGROUND: Patients with diabetes mellitus have a high mortality...... following AMI, probably due to a high risk of congestive heart failure and reinfarction. Because ACE inhibition effectively reduces progression of heart failure, it could be particularly beneficial in diabetic patients after AMI. METHODS: The study is a retrospective analysis using data from.......21 to 0.67]), and no significant reduction of this end point was found in the nondiabetic group. CONCLUSIONS: The ACE inhibition after myocardial infarction complicated by left ventricular dysfunction appears to be of considerable importance in patients with diabetes mellitus by saving lives...

  1. Scleroderma renal crisis during intravenous cyclophosphamide pulse therapy for complicated interstitial lung disease was successfully treated with angiotensin converting enzyme inhibitor and plasma exchange.

    Nagamura, Norihiro; Kin, Seikon

    2016-08-01

    Systemic sclerosis (SSc) is a multiorgan disorder involving the skin, heart, lungs, kidneys, and intestines. Progressive interstitial lung disease (ILD) is a serious complication in SSc patients, and cyclophosphamide (CYC) is the only recommended therapy for this condition;(1)) however, its clinical effectiveness is not sufficient. Scleroderma renal crisis (SRC) is a rare complication, characterized by acute renal failure and progressive hypertension. Angiotensin-converting-enzyme inhibitor (ACE-i) is a widely accepted therapy for SRC. We report an SSc patient with SRC and progressive ILD who underwent treatment with CYC and successful treatment with ACE-i and plasma exchange (PE). SRC and ILD are significant contributors to morbidity and mortality among SSc patients, and the therapy for these disorders is of great interest to rheumatologists. This study presents the possibility of favorable effects of PE for SSc-associated ILD and SRC. PMID:27578917

  2. Incidence and influencing factors of aldosterone breakthrough during therapy with angiotensin Ⅱ receptor bockers alone,or combined with angiotensin-converting enzyme inhibitors in patients with non-diabetic nephropathy

    梁敏

    2013-01-01

    Objective To investigate the incidence and influen-cing factors of aldosterone breakthrough during therapy with angiotensin Ⅱ receptor blockers(ARB) alone,or combined with angiotensin-converting enzyme inhibitors(ACEI) in Chinese patients with non-diabetic

  3. Effects of the angiotensin-converting enzyme inhibitor enalapril on sympathetic neuronal function and β-adrenergic desensitization in heart failure after myocardial infarction in rats

    One of the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure may derive from sympathoinhibition and the prevention of β-adrenergic desensitization. However, the roles of these properties in the overall effects of ACE inhibitor are not clear. We studied the effects of chronic enalapril treatment (20 mg/L in drinking water for 12 weeks) on left ventricular (LV) function, cardiac norepinephrine (NE), sympathetic neuronal function assessed by 131I-metaiodobenzylguanidine (MIBG), β-receptors, and isometric contraction of papillary muscle in rats with myocardial infarction (MI) induced by coronary artery ligation. Decreased LV function in the MI rats was associated with reduced cardiac NE content and MIBG uptake, and severely blunted responses of non-infarcted papillary muscle to isoproterenol, forskolin, and calcium. Enalapril attenuated LV remodeling in association with a reduction of the ventricular loading condition and restored baseline developed tension of non-infarcted papillary muscle to the level of sham-operated rats. However, enalapril did not improve cardiac NE content, MIBG uptake, or inotropic responsiveness to β-agonists. These results suggest that the major effect of the ACE inhibitor enalapril in the treatment of heart failure is not due to sympathoinhibition or restoration of β-adrenergic pathway in this model of heart failure. (author)

  4. Characterization of angiotensin converting enzyme (ACE) in the testis and assessment of the in vivo effects of the ACE inhibitor perindopril

    Jackson, B.; Cubela, R.B.; Sakaguchi, K.; Johnston, C.I.

    1988-07-01

    Angiotensin converting enzyme (ACE) was characterized by radioligand studies utilizing the potent ACE inhibitor 351A, a derivative of lisinopril. Ligand binding characteristics were similar for ACE derived from testis, lung, and kidney, despite known differences in structure between ACe from these sources. This observation suggests that the ACE active enzymatic site is similar in different tissues. The effect of the orally active ACE inhibitor perindopril was studied ex vivo in tissues of the rat after oral gavage. Radioligand bound to tissue ACE was reduced after perindopril treatment, in tissue homogenates of lung and kidney, but not testis. Autoradiographs of radioligand binding to tissue sections obtained ex vivo after oral perindopril showed inhibition of ACE in the aorta, lung, and kidney, but did not reveal any inhibition of ACE in the testis. ACE in small vessels of the testis was inhibited as in the aorta, while at the same time testicular ACE was unaffected. ACE in rat testis appears to have a similar enzymatic binding site to ACE from the lung and kidney. Perindopril inhibited ACE in the lung and kidney but did not affect ACE in the testis, suggesting the drug is limited in testicular penetration by the blood-testis barrier. This may explain the lack of any reports of adverse effects of ACE inhibitors on testicular function.

  5. Mitochondrial uncoupling proteins regulate angiotensin-converting enzyme expression

    Dhamrait, Sukhbir S; Maubaret, Cecilia; Pedersen-Bjergaard, Ulrik;

    2016-01-01

    Uncoupling proteins (UCPs) regulate mitochondrial function, and thus cellular metabolism. Angiotensin-converting enzyme (ACE) is the central component of endocrine and local tissue renin-angiotensin systems (RAS), which also regulate diverse aspects of whole-body metabolism and mitochondrial...

  6. Angiotensin-converting enzyme inhibitor prevents oxidative stress, inflammation, and fibrosis in carbon tetrachloride-treated rat liver.

    Reza, Hasan Mahmud; Tabassum, Nabila; Sagor, Md Abu Taher; Chowdhury, Mohammed Riaz Hasan; Rahman, Mahbubur; Jain, Preeti; Alam, Md Ashraful

    2016-01-01

    Hepatic fibrosis is a common feature of chronic liver injury, and the involvement of angiotensin II in such process has been studied earlier. We hypothesized that anti-angiotensin II agents may be effective in preventing hepatic fibrosis. In this study, Long Evans female rats were used and divided into four groups such as Group-I, Control; Group-II, Control + ramipril; Group-III, CCl4; and Group-IV, CCl4 + ramipril. Group II and IV are treated with ramipril for 14 d. At the end of treatment, the livers were removed, and the level of hepatic marker enzymes (aspartate aminotransferase, Alanine aminotransferase, and alkaline phosphatase), nitric oxide, advanced protein oxidation product , catalase activity, and lipid peroxidation were determined. The degree of fibrosis was evaluated through histopathological staining with Sirius red and trichrome milligan staining. Carbon-tetrachloride (CCl4) administration in rats developed hepatic dysfunction and raised the hepatic marker enzymes activities significantly. CCl4 administration in rats also produced oxidative stress, inflammation, and fibrosis in liver. Furthermore, angiotensinogen-inhibitor ramipril normalized the hepatic enzymes activities and improved the antioxidant enzyme catalase activity. Moreover, ramipril treatment ameliorated lipid peroxidation and hepatic inflammation in CCl4-treated rats. Ramipril treatment also significantly reduced hepatic fibrosis in CCl4-administered rats. In conclusion, our investigation suggests that the antifibrotic effect of ramipril may be attributed to inhibition of angiotensin-II mediated oxidative stress and inflammation in liver CCl4-administered rats. PMID:26862777

  7. Interferon augments the anti-fibrotic activity of an angiotensin-converting enzyme inhibitor in patients with refractory chronic hepatitis C

    Hitoshi Yoshiji; Masaharu Yamazaki; Masahisa Toyohara; Akira Mitoro; Hiroshi Fukui; Ryuichi Noguchi; Hideyuki Kojima; Yasuhide Ikenaka; Mitsuteru Kitade; Kosuke Kaji; Masahito Uemura; Junichi Yamao; Masao Fujimoto

    2006-01-01

    AIM:To evaluate the effect of combination treatment with the interferon (IFN) and angiotensin-converting enzyme inhibitor (ACE-I ) on several fibrotic indices in patients with refractory chronic hepatitis C (CHC).METHODS: Perindopril (an ACE-I; 4 mg/d) and/or natural IFN (3 MU/L; 3 times a week) were administered for 12 mo to refractory CHC patients, and several indices of serum fibrosis markers were analyzed.RESULTS:ACE-Ⅰ decreased the serum fibrosis markers,whereas single treatment with IFN did not exert these inhibitory effects. However, IFN significantly augmented the effects of ACE-Ⅰ, and the combination treatment exerted the most potent inhibitory effects. The serum levels of alanine transaminase and HCV-RNA were not significantly different between the groups, whereas the plasma level of transforming growth factor-β was significantly attenuated almost in parallel with suppression of the serum fibrosis markers.CONCLUSION:The combination therapy of an ACE-Ⅰand IFN may have a diverse effect on disease progression in patients with CHC refractory to IFN therapy through its anti-fibrotic effect.

  8. Combined treatment of vitamin K2 and angiotensin-converting enzyme inhibitor ameliorates hepatic dysplastic nodule in a patient with liver cirrhosis

    Hitoshi Yoshiji; Kosuke Kaji; Masahito Uemura; Junichi Yamao; Masao Fujimoto; Akira Mitoro; Masahisa Toyohara; Motoyuki Yoshida; Hiroshi Fukui; Ryuichi Noguchi; Masaharu Yamazaki; Yasuhide Ikenaka; Masayoshi Sawai; Masatoshi Ishikawa; Hideto Kawaratani; Tsuyoshi Mashitani; Mitsuteru Kitade

    2007-01-01

    Although it is well known that the hepatocellular carcinoma (HCC) is an ominous complication in patients with liver cirrhosis, there has been no approved drug to prevent the development of HCC to date. We previously reported that the combined treatment of vitamin K2 (VK) and angiotensin-converting enzyme inhibitor(ACE-I) significantly suppressed the experimental hepatocarcinogenesis. A 66-year-old Japanese woman with hepatitis C virus (HCV)-related liver cirrhosis developed a dysplastic nodule in the liver detected by enhanced computed tomography along with elevation of the tumor markers, namely, alpha-fetoprotein (AFP)and lectin-reactive demarcation (AFP-L3), suggesting the presence of latent HCC. After oral administration of VK and ACE-I, the serum levels of both AFP and AFP-L3 gradually decreased without any marked alteration of the serum aminotransferase activity. After one-year treatment, not only the serum levels of AFP and AFP-L3 returned to the normal ranges, but also the dysplastic nodule disappeared. Since both VK and ACE-I are widely used without serious side effects, this combined regimen may become a new strategy for chemoprevention against HCC.

  9. Use of beta-blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and breast cancer survival: Systematic review and meta-analysis.

    Raimondi, Sara; Botteri, Edoardo; Munzone, Elisabetta; Cipolla, Carlo; Rotmensz, Nicole; DeCensi, Andrea; Gandini, Sara

    2016-07-01

    Breast cancer (BC) is the second leading cause of cancer death among women in Western Countries. Beta-blocker (BB) drugs, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) were suggested to have a favorable role in the development and progression of BC. We have performed a meta-analysis to clarify the potential benefits of these drugs on BC survival. A total number of 46 265 BC patients from eleven papers were included, ten independent studies on BB use and seven on ACEi/ARB use. The summary hazard ratio (SHR) was estimated by pooling the study-specific estimates with random effects models and maximum likelihood estimation. We assessed the homogeneity of the effects across studies and evaluated between-study heterogeneity by meta-regression and sensitivity analyses. We found a significant improvement in BC specific survival for patients treated with BB drugs at the time of BC diagnosis (SHR: 0.44; 95%CI: 0.26-0.73 with I(2)  = 78%). We also observed a borderline significant improvement in disease free survival for subjects treated with BB (SHR: 0.71, 95%CI: 0.19-1.03). No association of ACEi/ARB use with disease free and overall survival was found. In conclusion, we report epidemiological evidence that BB improve BC-specific survival. Clinical trials addressing this hypothesis are warranted. PMID:26916107

  10. Utility of copper(II) oxide as a packed reactor in flow injection assembly for rapid analysis of some angiotensin converting enzyme inhibitors

    Emara, Samy; El-Gindy, Alaa; El-Shorbagi, Abdel-Nasser; Hadad, Ghada

    2003-08-11

    A new simple, sensitive, rapid and precise flow injection (FI) procedure based on the formation of copper complexes with some angiotensin converting enzyme (ACE) inhibitors has been developed and evaluated for the analysis of lisinopril (LN), enalapril maleate (EP), ramipril (RP) and perindopril tert-butylamine (PD). In this method, samples were injected into a flowing stream of distilled-deionized water, carried through the packed reactor of CuO for derivatization followed by ultraviolet (UV) detection. The flow rate was 1.5 ml min{sup -1} and column temperature was ambient (25 deg. C). Lisinopril was injected directly into the flowing stream and the detector response was measured at 262 nm. The hydrolysis products of enalapril maleate, ramipril and perindopril tert-butylamine in 0.2N NaOH were injected after neutralization with 1N HCl and the detector response was measured at 272, 265 and 252 nm, respectively. The developed method was successfully applied to the determination of tested drugs in pharmaceutical preparations at a sampling rate of 60 samples h{sup -1} and a recovery near 100% for all compounds.

  11. 21 CFR 862.1090 - Angiotensin converting enzyme (A.C.E.) test system.

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Angiotensin converting enzyme (A.C.E.) test system... Test Systems § 862.1090 Angiotensin converting enzyme (A.C.E.) test system. (a) Identification. An angiotensin converting enzyme (A.C.E.) test system is a device intended to measure the activity of...

  12. Cardiac metaiodobenzylguanidine activity can predict the long-term efficacy of angiotensin-converting enzyme inhibitors and/or beta-adrenoceptor blockers in patients with heart failure

    Nakata, Tomoaki; Wakabayashi, Takeru; Kyuma, Michifumi; Takahashi, Toru; Tsuchihashi, Kazufumi; Shimamoto, Kazuaki [Sapporo Medical University School of Medicine, Second Department of Internal Medicine (Cardiology), Sapporo (Japan)

    2005-02-01

    Although the benefits of treatment with angiotensin-converting enzyme (ACE) inhibitors and beta-blockers are well known, no method has as yet been established to predict the efficacy of drug therapy. This study tested whether cardiac{sup 123}I-metaiodobenzylguanidine (MIBG) activity is of prognostic value and can predict the improvement in heart failure patients resulting from treatment with ACE inhibitors and/or beta-blockers. Following quantification of the heart-to-mediastinum ratio (HMR) of MIBG activity, 88 patients with heart failure who were treated with ACE inhibitors and/or beta-blockers (treated group) and 79 patients with heart failure who were treated conventionally without the aforementioned agents, and who served as controls, were followed up for 43 months with a primary endpoint of cardiac death. The treated group had a significantly lower prevalence of cardiac death and a significantly lower mortality at 5 years compared with the control group (15% vs 37% and 21% vs 42%, p<0.05, respectively). Multivariate analysis revealed that significant predictors were HMR, age, nitrate use and ventricular tachycardia for the treated group, and HMR, nitrate use and NYHA class for the control group. The drug treatment significantly reduced mortality from 36% to 12% when HMR was 1.53 or more and from 53% to 37% when HMR was less than 1.53. The reduction in risk of mortality within 5 years in patients without a severe MIBG defect (67%) was twice that in patients with such a defect (32%) (p<0.05). The reduction in mortality risk achieved by using ACE inhibitors and/or beta-blockers is associated with the severity of impairment of cardiac MIBG uptake. Cardiac MIBG activity can consequently be of long-term prognostic value in predicting the effectiveness of such treatment in patients with heart failure. (orig.)

  13. Angiotensin-converting enzymes modulate aphid–plant interactions

    Wei Wang; Lan Luo; Hong Lu; Shaoliang Chen; Le Kang; Feng Cui

    2015-01-01

    Angiotensin-converting enzymes (ACEs) are key components of the renin–angiotensin system in mammals. However, the function of ACE homologs in insect saliva is unclear. Aphids presumably deliver effector proteins via saliva into plant cells to maintain a compatible insect–plant interaction. In this study, we showed that ACE modulates aphid–plant interactions by affecting feeding behavior and survival of aphids on host plants. Three ACE genes were identified from the pea aphid Acyrthosiphon pis...

  14. Silica Exposure and Serum Angiotensin Converting Enzyme Activity

    YK Sharma; AB Karnik; RR Tiwari

    2010-01-01

    Background: Silicosis is known in industrial workers for centuries. Till recently, the mainstay of its diagnosis and progress was clinical examination of the respiratory system, pulmonary function test and chest radiography. Several biomarkers such as serum angiotensin converting enzyme (ACE) activity have been examined to determine the extent of silicosis. Objective: To elucidate the effect of age, gender, duration of exposure to silica dust, smoking habit, and pulmonary function status on t...

  15. Long-term effects of the angiotensin-converting enzyme inhibitor enalapril on chronic heart failure. Examination by {sup 123}I-MIBG imaging

    Soeki, Takeshi; Tamura, Yoshiyuki; Bandou, Kanji; Tanaka, Hideji; Takeichi, Naoki; Shinohara, Hisanori; Yui, Yasuko; Fukuda, Nobuo; Sui, Osamu [Zentsuji National Hospital, Kagawa (Japan)

    1998-11-01

    To examine the long-term effects of the angiotensin-converting enzyme (ACE) inhibitor enalapril on chronic heart failure, 10 patients (7 men and 3 women, mean age: 62{+-}11 years) with chronic stable heart failure, classified as New York Heart Association (NYHA) functional class 2-3 for more than 3 months, and a left ventricular ejection fraction less than 45% were treated with 2.5-5.0 mg of enalapril once a day for 3-15 months (mean 7 months). The causes of heart failure were old myocardial infarction (n=7), hypertension (n=2), and atrial fibrillation (n=1). Radioiodinated metaiodobenzyl guanidine ({sup 123}I-MIBG) imaging, radionuclide angiography, and treadmill exercise test were performed before and after the treatment. With enalapril treatment, left ventricular ejection fraction (LVEF) increased significantly from 38.3{+-}6.9% to 47.5{+-}14.7%; sub-maximal exercise time increased significantly from 205{+-}112 to 272{+-}120 seconds; the heart to mediastinum (H/M) ratio of {sup 123}I-MIBG increased significantly (early image: 1.99{+-}0.38 versus 2.20{+-}0.50; delayed image: 1.86{+-}0.44 versus 2.09{+-}0.51); and the washout rate of {sup 123}I-MIBG decreased slightly from 29.1{+-}9.1% to 25.4{+-}7.0%. The improvement rate of LVEF was significantly correlated with the improvement rates of the H/M ratio and washout rate after treatment with enalapril. Thus, the long-term effects of enalapril can be observed in the cardiac sympathetic nervous system, and {sup 123}I-MIBG imaging appears to be useful for evaluating the therapeutic effects of enalapril on the cardiac sympathetic nervous system in patients with chronic heart failure. (author)

  16. Long-term effects of the angiotensin-converting enzyme inhibitor enalapril on chronic heart failure. Examination by 123I-MIBG imaging

    To examine the long-term effects of the angiotensin-converting enzyme (ACE) inhibitor enalapril on chronic heart failure, 10 patients (7 men and 3 women, mean age: 62±11 years) with chronic stable heart failure, classified as New York Heart Association (NYHA) functional class 2-3 for more than 3 months, and a left ventricular ejection fraction less than 45% were treated with 2.5-5.0 mg of enalapril once a day for 3-15 months (mean 7 months). The causes of heart failure were old myocardial infarction (n=7), hypertension (n=2), and atrial fibrillation (n=1). Radioiodinated metaiodobenzyl guanidine (123I-MIBG) imaging, radionuclide angiography, and treadmill exercise test were performed before and after the treatment. With enalapril treatment, left ventricular ejection fraction (LVEF) increased significantly from 38.3±6.9% to 47.5±14.7%; sub-maximal exercise time increased significantly from 205±112 to 272±120 seconds; the heart to mediastinum (H/M) ratio of 123I-MIBG increased significantly (early image: 1.99±0.38 versus 2.20±0.50; delayed image: 1.86±0.44 versus 2.09±0.51); and the washout rate of 123I-MIBG decreased slightly from 29.1±9.1% to 25.4±7.0%. The improvement rate of LVEF was significantly correlated with the improvement rates of the H/M ratio and washout rate after treatment with enalapril. Thus, the long-term effects of enalapril can be observed in the cardiac sympathetic nervous system, and 123I-MIBG imaging appears to be useful for evaluating the therapeutic effects of enalapril on the cardiac sympathetic nervous system in patients with chronic heart failure. (author)

  17. Effect of angiotensin converting enzyme inhibitor on the calcium transients and calcium handling proteins in ventricular myocytes from rats with heart failure

    WANG Li-chun; ZENG Wu-tao; LIU Jun; DONG Yu-gang; TANG An-li; FENG Chong; MA Hong; HE Jian-gui; LIAO Xin-xue; CHEN Wen-fang; LENG Xiu-yu; MA Li; MAI Wei-yi; TAO Jun

    2005-01-01

    Background Chronic heart failure (CHF) is associated with calcium transients and calcium handling proteins. Angiotensin converting enzyme (ACE) inhibitor has been demonstrated to have beneficial effect on CHF. Yet studies addressed to the relationship between ACE inhibitor and calcium transients in CHF are rare. The aim of this study was to investigate the influence of ACE inhibitor (perindopril) on the contractility and calcium transients and calcium handling proteins in ventricular myocytes from rats with experimental heart failure.Results The fraction of cell shortening (FS%) and [Ca2+]imax (nmol/L) were significantly reduced in group CHF-C compared with group PS (FS%: 7.51±1.15 vs 13.21±1.49;[Ca2+]imax:330.85±50.05 vs 498.16±14.07; both P<0.01), and restored at least partially in CHF-T group. In CHF-C group, the left ventricular mRNA of NCX1 and PLB were significantly upregulated in comparing with PS group (RNCX1/β-Actin: 0.51±0.12 vs 0.19±0.06, P<0.01; RPLB/β-Actin: 0.26±0.12 vs 0.20±0.08, P<0.05), while SERCA2 mRNA was downregulated (0.48±0.10 vs 0.80±0.11, P<0.01). The mRNA levels of NCX1 and SERCA2 in CHF-T group were between the CHF-C and PS group, and the differences of the latter two groups were significant (all P<0.05). In CHF-C and CHF-T groups, the protein expression of NCX1 were 1.141±0.047 and 1.074±0.081 times of that in PS group respectively (both P<0.05), and SERCA2 protein levels were 0.803±0.100 and 0.893±0.084 times of that in PS group respectively (both P<0.05). The protein expression of NCX1 and SERCA2 in the CHF-C and CHF-T groups is significantly different (both P<0.05).Conclusion ACE inhibitor could improve cardiac function of failing heart through directly enhancing the contractility of single cardiomyocyte, and these effects are probably mediated by its roles in preventing the deleterious changes of calcium transients and calcium handling proteins in CHF.

  18. Comparative study on the ACE inhibitors Quinapril and Captopril for the (Angiotensin converting enzyme) treatment of the decompensated cardiac insufficiency in dog

    In a randomized study of 52 dogs the efficacy and safety of captopril and quinapril in the treatment of canine heart failure is studied. The drugs were found to be comparably effective. The recommended dosage schedule for the short acting captopril is three times daily 0.5 mg/kg body weight. Quinapril belongs to a newer generation of ACE inhibitors with a longer half life than captopril and the treatment was started with a single dose of 0.5 mg/kg body weight. This dosage schedule was sufficient for the successful therapy of most of the dogs with heart failure phase II (12 of 13), but in 4 of 7 dogs with heart failure phase III and in all of the patients with phase IV the single dose had to be increased and/or the dosing interval of quinapril had to be shortened, because they still showed complaints due to heart failure. We recommend to adjust the dosage schedule of quinapril individually to the severity of heart failure. Therapy should be started once daily with an application of 0,5 mg/kg body weight and the dog should be controlled about one week later. If there are still symptoms of decompensated heart failure, the dosage may be increased gradually until a maximum dosage of 0.5 mg/kg three times daily. Especially for patients with severe heart failure we recommend at least when treatment is started a concomitant diuretic therapy. Echocardiographic evaluation of cardiac function shows if there is an indication for positive inotropic support witha digitalis glycoside. Quinapril, a novel inhibitor of the angiotensin-converting enzyme can ease the management of canine heart failure, because at least in dogs with mild to moderate heart failure dosing interval is longer compared with captopril. Moreover, quinapril is available as 5 mg tablets whereas the smallest captopril tablets contain 12.5 mg agent. It has to be mentioned that expenses for a treatment with ACE inhibitors are significantly higher than for a therapy with digitalis, so frequently above all the

  19. Lung angiotensin converting enzyme activity in rats with pulmonary hypertension.

    Keane, P. M.; Kay, J M; Suyama, K L; Gauthier, D.; Andrew, K

    1982-01-01

    We have studied serum and lung tissue angiotensin converting enzyme (ACE) activity in female Wistar rats with pulmonary hypertension induced by two different methods. Chronic pulmonary hypertension was produced in one group of 10 rats (CH) by confinement in a hypobaric chamber (380 mmHg) for three weeks, and in another group fo 10 rats (M) by a single subcutaneous injection of monocrotaline (60 mg/kg body weight). In these two groups of tests rats and in 20 untreated controls (C), we evaluate...

  20. Lung angiotensin converting enzyme activity in chronically hypoxic rats.

    Kay, J M; Keane, P. M.; Suyama, K L; Gauthier, D.

    1985-01-01

    A study was carried out to test the hypothesis that the reduced lung angiotensin converting enzyme (ACE) activity which occurs in chronic hypoxia is related to the development of pulmonary hypertension rather than to hypoxia per se. Right ventricular mean systolic pressure (Prvs, mm Hg) and ACE activity (nmol/mg protein/min) in lung tissue homogenates were measured in seven groups of four rats placed in a hypobaric chamber (380 mm Hg; 51 kPa) for two to 24 days. Identical measurements were ma...

  1. Effects of angiotensin converting enzyme inhibitor, angio- tensin II type I receptor blocker and their combination on postinfarcted ventricular remodeling in rats

    2006-01-01

    Background Transforming growth factor (TGF) β1-Smads signal plays an important role in cardiac remodeling following myocardial infarction (MI). In addition, both angiotensin converting enzyme inhibitor (ACEI) and angiotensin II type I receptor blocker (ARB) can effectively prevent left ventricular remodeling. The current study focused on whether the combination of ACEI and ARB is more beneficial for preventing ventricular remodeling and whether Smad proteins mediate this beneficial effect.Results VW/BW significantly increased in the placebo groups compared with that in the control group (P<0.01). This increase was limited in ACEI, ARB, and combined groups (P<0.01 compared with placebo group). There was no significant difference among the three actively treated groups. Collagen was increased in placebo group (5.68±0.5)% compared with that in control group (P<0.01). ACEI, ARB and combined treatment attenuated this increase of collagen [(4.3±0.5)%, (3.5±0.5)%, (3.2±0.4)%] in comparison with that in placebo group (P<0.01 respectively). Combined treatment showed more significant effect on collagen deposition. EF and FS significantly decreased, LVDd and E/A significantly increased in placebo group compared with that in control group (P<0.01 respectively). ACEI, ARB and combined treatment ameliorated these indexes (P<0.01 compared with placebo group). The mRNA expression of TGFβ1, Smad 2, and Smad 3 (0.700±0.045, 0.959±0.037 and 0.850±0.051) increased in placebo group compared with that in control group (P<0.01). ACEI, ARB and combined treatment normalized the increase (P<0.01). Furthermore, ARB and combined treatment proved to be more effective in decreasing TGF β1 and Smad mRNA expression than ACEI treatment (P<0.01). The expression of Smad 2 and Smad 3 protein increased in placebo group compared with that in control group (P<0.01). ACEI, ARB and combined treatment normalized the increase (P<0.01). Furthermore, ARB and combined treatment proved to be more

  2. Impact of drug price adjustments on utilization of and expenditures on angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in Taiwan

    Huang Shiou-Huei

    2012-05-01

    Full Text Available Abstract Background A previous study has suggested that drug price adjustments allow physicians in Taiwan to gain greater profit by prescribing generic drugs. To better understand the effect of price adjustments on physician choice, this study used renin-angiotensin drugs (including angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin receptor blockers [ARBs] to examine the impact of price adjustments on utilization of and expenditures on patented and off-patent drugs with the same therapeutic indication. Methods Using the Taiwan’s Longitudinal Health Insurance Database (2005, we identified 147,157 patients received ACEIs and/or ARBs between 1997 and 2008. The annual incident and prevalent users of ACEIs, ARBs and overall renin-angiotensin drugs were examined. Box-Tiao intervention analysis was applied to assess the impact of price adjustments on monthly utilization of and expenditures on these drugs. ACEIs were divided into patented and off-patent drugs, off-patent ACEIs were further divided into original brands and generics, and subgroup analyses were performed. Results The number of incident renin-angiotensin drug users decreased over the study period. The number of prevalent ARB users increased and exceeded the cumulative number of first-time renin-angiotensin drug users starting on ARBs, implying that some patients switched from ACEIs to ARBs. After price adjustments, long term trend increases in utilization were observed for patented ACEIs and ARBs; a long-term trend decrease was observed for off-patent ACEIs; long-term trend change was not significant for overall renin-angiotensin drugs. Significant long-term trend increases in expenditures were observed for patented ACEIs after price adjustment in 2007 (200.9%, p = 0.0088 and in ARBs after price adjustments in 2001 (173.4%, p  Conclusions Price adjustments did not achieve long-term cost savings for overall renin-angiotensin drugs. Possible switching from ACEIs to ARBs

  3. Demonstration of extrapulmonary activity of angiotensin converting enzyme in intact tissue preparations.

    Lembeck, F.; Griesbacher, T; Eckhardt, M.

    1990-01-01

    1. The activity of angiotensin converting enzyme (ACE) has been studied on functional parameters of intact isolated preparations of extrapulmonary tissues. The conversion of angiotensin I (A I) to angiotensin II (A II) and the cleavage of bradykinin (BK) were used as indicators of ACE activity. Captopril was employed as a specific inhibitor of ACE. 2. Captopril augmented the BK-induced contractions of the rat isolated uterus, the BK- and substance P-induced contractions of the guinea-pig ileu...

  4. Effects of angiotensin-converting enzyme inhibition and bradykinin peptides in rats with myocardial infarction

    Qu, Zhe; Xu, Hongxin; Tian, Yihao

    2015-01-01

    Background and objective: Angiotensin-converting enzyme (ACE) inhibitors have been reported to decrease myocardial remodeling and faciliate cardiac function improvement in the setting myocardial infarction by affecting bradykinin. The purpose of this study was to evaluate the combination effects of perindopril and bradykinin (BK) in rats with myocardial infarction. Methods: Wistar Rats underwent to left anterior descending (LAD) coronary artery ligation were allocated into MI group (n = 6); P...

  5. Radioimmunoassay of a new angiotensin-converting enzyme inhibitor (perindopril) in human plasma and urine: Advantages of coupling anion-exchange column chromatography with radioimmunoassay

    Doucet, L.; De Veyrac, B.; Delaage, M.; Cailla, H.; Bernheim, C.; Devissaguet, M. (Immunotech S. A. Case 915, Marseille (France))

    1990-08-01

    Perindopril (P) is a prodrug whose active metabolite perindoprilat (PT) is an antihypertensive agent which acts by inhibition of angiotensin-converting enzyme (ACE). Anti-PT antiserum was produced in a rabbit immunized against PT that was covalently linked to bovine serum albumin. The radioligand is an iodinated ({sup 125}I) derivative of PT-glycyltyrosinamide. Both the drug (PT) and the prodrug (P) are assayed in the same sample; PT is assayed as is and P is assayed after quantitative alkaline hydrolysis into PT. Certain data obtained from such assays suggest the occurrence in plasma and urine of a third immunoreactive component. A chromatographic fractionation of samples allowed us to isolate a new immunoreactive metabolite which was further identified as a glucuronide of PT (PT-G). Therefore, the whole assay was carried out as follows: biological samples were fractionated by stepwise chromatography on a anion-exchange resin (the first fraction contained P, the second contained PT, and the third contained PT-G); and RIA was performed on fractions 2 and 3 as is, and on fraction 1 after alkaline hydrolysis. Performances and assessments of this method are presented together with an example of a pharmacokinetic profile.

  6. The effect of esmolol on corrected-QT interval, corrected-QT interval dispersion changes seen during anesthesia induction in hypertensive patients taking an angiotensin-converting enzyme inhibitor

    Zahit Çeker

    2015-02-01

    Full Text Available BACKGROUND AND OBJECTIVES: The importance of minimizing the exaggerated sympatho-adrenergic responses and QT interval and QT interval dispersion changes that may develop due to laryngoscopy and tracheal intubation during anesthesia induction in the hypertensive patients is clear. Esmolol decreases the hemodynamic response to laryngoscopy and intubation. However, the effect of esmolol in decreasing the prolonged QT interval and QT interval dispersion as induced by laryngoscopy and intubation is controversial. We investigated the effect of esmolol on the hemodynamic, and corrected-QT interval and corrected-QT interval dispersion changes seen during anesthesia induction in hypertensive patients using angiotensin converting enzyme inhibitors. METHODS: 60 ASA I-II patients, with essential hypertension using angiotensin converting enzyme inhibitors were included in the study. The esmolol group received esmolol at a bolus dose of 500 mcg/kg followed by a 100 mcg/kg/min infusion which continued until the 4th min after intubation. The control group received 0.9% saline similar to the esmolol group. The mean blood pressure, heart rate values and the electrocardiogram records were obtained as baseline values before the anesthesia, 5 min after esmolol and saline administration, 3 min after the induction and 30 s, 2 min and 4 min after intubation. RESULTS: The corrected-QT interval was shorter in the esmolol group (p = 0.012, the corrected-QT interval dispersion interval was longer in the control group (p = 0.034 and the mean heart rate was higher in the control group (p = 0.022 30 s after intubation. The risk of arrhythmia frequency was higher in the control group in the 4-min period following intubation (p = 0.038. CONCLUSION: Endotracheal intubation was found to prolong corrected-QT interval and corrected-QT interval dispersion, and increase the heart rate during anesthesia induction with propofol in hypertensive patients using angiotensin converting

  7. Effects on plasma angiotensin-converting enzyme activity and circulating renin of lisinopril and enalapril alone and in combination with propranolol in healthy volunteers

    Hansen, Erik Feldager; Bendtsen, Flemming; Henriksen, Jens Henrik

    1999-01-01

    The effects on plasma angiotensin-converting enzyme activity and renin activity of the two long-acting angiotensin-converting enzyme inhibitors, lisinopril and enalapril, alone and in combination with propranolol were studied. In an open, randomised, cross-over design 12 healthy volunteers received...... orally enalapril 20 mg alone, enalapril 20 mg in combination with propranolol 80 mg, lisinopril 20 mg alone, and lisinopril 20 mg in combination with propranolol 80 mg. Plasma angiotensin-converting enzyme activity and plasma renin activity were measured for 24 h after each treatment period. Lisinopril...

  8. EFFECTS OF EARLY ANGIOTENSIN-CONVERTING ENZYME-INHIBITION IN A PIG MODEL OF MYOCARDIAL-ISCHEMIA AND REPERFUSION

    VANWIJNGAARDEN, J; TOBE, TJM; WEERSINK, EGL; BEL, KJ; DEGRAEFF, PA; DELANGEN, CDJ; VANGILST, WH; WESSELING, H

    1992-01-01

    In a blind, randomized study, the effects of perindopril, a nonsulfhydryl-containing angiotensin-converting enzyme (ACE) inhibitor, were compared with those of placebo in a closed-chest pig model of myocardial infraction. In anesthetized pigs, my ocardinal ischemia and reperfusion were induced by in

  9. Effects of aspirin on angiotensin-converting enzyme inhibition and left ventricular dilation one year after acute myocardial infarction

    Oosterga, M; Anthonio, RL; de Kam, PJ; Kingma, JH; Crijns, HJGM; van Gilst, WH

    1998-01-01

    There are conflicting reports on the interaction of aspirin with angiotensin-converting enzyme inhibitors in heart failure and systemic hypertension. A past hoc analysis of the Captopril and Thrombolysis Study (CATS) study was conducted. At randomization, 94 patients (31.5%) took aspirin. In patient

  10. Angiotensin-converting enzyme kinetics in an endothelial cell column

    The kinetics of saturable endothelial metabolic functions have been assessed in vivo by transient (indicator-dilution) measurements and in culture by steady-state measurements, but comparisons between the two are difficult. Therefore, we used indicator-dilution methods to assess the kinetics of angiotensin-converting enzyme (ACE) activity in cultured endothelium. Bovine fetal aortic endothelial cells were grown to confluence on microcarrier beads. Cell-covered beads were poured into polypropylene columns and perfused with serum-free culture medium. Six injections, containing [3H]benzol-Phe-Ala-Pro [( 3H]BPAP, an ACE substrate) and varying amounts of unlabeled BPAP, were applied to each column and effluent was collected in serial samples. The apparent kinetics of BPAP metabolism were determined by four models used previously to determine pulmonary endothelial ACE kinetics in vivo, the most useful model incorporating transit time heterogeneity. The Km averaged 5 microM, which is close to values determined previously in vivo and in vitro. The Amax (Vmax.reaction volume) and Amax/Km averaged 6 nmol/min and 1.5 ml/min, respectively, which are lower than estimates in vivo. In conclusion, we have developed a new method for investigating saturable metabolic activity in cultured endothelium, which after further exploration should also enable better comparisons of endothelial metabolic functions in vivo and in culture

  11. 植物源血管紧张素转换酶抑制剂的研究进展%Review on Angiotensin Converting Enzyme Inhibitors Derived from Plants

    蒋丹; 赵楠楠; 赵英; 张佳蓉

    2015-01-01

    血管紧张素转换酶抑制剂(Angiotensin converting enzyme inhibitors,ACEI)通过肾素-血管紧张素系统(RAS)和激肽释放酶-肽酶系统(KKS),抑制血管紧张素Ⅱ的生成,减少缓激肽的降解,从而达到降血压的目的;植物来源的天然化合物具有来源广泛、结构多样、特异性高、毒性低等特点,因而从植物中筛选安全有效的ACEI成为研究热点.在此综述了血管紧张素转换酶(ACE)的活性测定方法以及植物来源的不同结构类型的ACEI研究进展.

  12. 血管紧张素转化酶中药抑制剂的筛选模型研究%Establishment of three screening models of angiotensin converting enzyme inhibitors

    巩颖; 王灵芝; 史新元; 乔延江

    2011-01-01

    Objective: To establish and compare three in vitro screening models of angiotensin converting enzyme inhibitors (ACEI), and provide methodological basis for screening ACEI drugs from Chinese herbal medicine.Method: Three screening models were established using rat serum, pure angiotensin converting enzyme (ACE) and crude extract enzyme from rabbit lung as enzyme sources, respectively, with corresponding testing methods, and captopril as the positive drug.Result: The IC50 of captopril was 2.30 nmol · L-1 using rat serum as the enzyme;and 1.04 nmol · L-1 for ACE pure enzyme; and 1.40 nmol · L-1 for crude extract enzyme from rabbit lung.Conclusion: Results from the three screening models were all in accordance with literature reports.These models can be applied to in vitro pharmaceutical screening.The selection of suitable screening model depend on the experimental situation and the inherent characters of models.%目的:研究比较不同的血管紧张素转化酶抑制剂(ACEI)筛选模型,提供从中草药中快速筛选ACEI药物的方法.方法:以卡托普利为阳性药,分别以大鼠血清、血管紧张素转化酶(ACE)纯酶、兔肺ACE粗提物作为酶源,采用不同的检测方法,建立3种ACEI筛选模型,考察多种中药有效成分ACEI活性.结果:大鼠血清粗提酶液模型检测卡托普利IC50值为2.30 nmol·L-1:ACE纯酶模型检测卡托普利IC50值为1.04 nmol·L-1;兔肺ACE粗提物模型检测卡托普利IC50值为1.40nmol.L-1,3种ACE筛选模型线性关系均良好,模型建立成功.结论:3种模型均町用于中草药的体外活性筛选,但各有利弊,可根据中草药组分和筛选模型的特点选择快速有效的模型.

  13. Angiotensin converting enzyme inhibitor and HMG-CoA reductase inhibitor as adjunct treatment for persons with HIV infection: a feasibility randomized trial.

    Jason V Baker

    Full Text Available BACKGROUND: Treatments that reduce inflammation and cardiovascular disease (CVD risk among individuals with HIV infection receiving effective antiretroviral therapy (ART are needed. DESIGN AND METHODS: We conducted a 2 × 2 factorial feasibility study of lisinopril (L (10 mg daily vs L-placebo in combination with pravastatin (P (20 mg daily vs P-placebo among participants receiving ART with undetectable HIV RNA levels, a Framingham 10 year risk score (FRS ≥ 3%, and no indication for ACE-I or statin therapy. Tolerability and adherence were evaluated. Longitudinal mixed models assessed changes in blood pressure (BP, blood lipids, and inflammatory biomarkers from baseline through months 1 and 4. RESULTS: Thirty-seven participants were randomized and 34 [lisinopril/pravastatin (n=9, lisinopril/P-placebo (n=8, L-placebo/pravastatin (n=9, L-placebo/P-placebo (n=8] attended at least one follow-up visit. Participants were 97% male, 41% white, 67% were current smokers, and 65% were taking a protease inhibitor. Median age was 48 years, CD4 count 483 cells/mm(3, FRS 7.79%, total cholesterol 184 mg/dL, and LDL-C 95 mg/dL. There was no treatment difference for pravastatin vs P-placebo in total cholesterol, LDL-C, or any of the inflammatory biomarkers. Participants randomized to lisinopril vs. L-placebo had significant declines in diastolic BP (-3.3 mmHg, p=0.05, hsCRP (-0.61 µg/mL, p=0.02 and TNF-α (-0.17 pg/mL, p=0.04. Participants taking lisinopril vs L-placebo were more likely to report missed doses (88 vs 35%; p=0.001 and have adherence <90% by pill count (42 vs. 0%; p=0.02. Few participants from either group reported side effects (n=3 vs. n=1. CONCLUSIONS: The modest BP changes and decreased adherence with lisinopril and absence of lipid differences with pravastatin suggest future studies of these drug classes should consider a run-in period to assess adherence and use a different statin. Our results also indicate that ACE-I therapy may have anti

  14. Intrarenal Distributions and Changes of Angiotensin-Converting Enzyme and Angiotensin-Converting Enzyme 2 in Feline and Canine Chronic Kidney Disease

    MITANI, Sawane; Yabuki, Akira; Sawa, Mariko; Chang, Hye-Sook; YAMATO, Osamu

    2013-01-01

    ABSTRACT Angiotensin-converting enzyme (ACE) is a key enzyme in the renin-angiotensin system (RAS). ACE2 is a newly identified member of the RAS. The present immunohistochemical study focused on changes in intrarenal ACE and ACE2 immunoreactivity in feline and canine chronic kidney disease (CKD). ACE immunoreactivity was predominantly observed in the brush border of the proximal tubules in dogs and cats. ACE immunoreactivity was lower in CKD kidneys than in normal kidneys, and quantitative an...

  15. Beta-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, nitrate-hydralazine, diuretics, aldosterone antagonist, ivabradine, devices and digoxin (BANDAID(2) ): an evidence-based mnemonic for the treatment of systolic heart failure.

    Chia, N; Fulcher, J; Keech, A

    2016-06-01

    Heart failure causes significant morbidity and mortality, with recognised underutilisation rates of guideline-based therapies. Our aim was to review current evidence for heart failure treatments and derive a mnemonic summarising best practice, which might assist physicians in patient care. Treatments were identified for review from multinational society guidelines and recent randomised trials, with a primary aim of examining their effects in systolic heart failure patients on mortality, hospitalisation rates and symptoms. Secondary aims were to consider other clinical benefits. MEDLINE and EMBASE were searched using a structured keyword strategy and the retrieved articles were evaluated methodically to produce an optimised reference list for each treatment. We devised the mnemonic BANDAID (2) , standing for beta-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, nitrate-hydralazine (or potentially neprilysin inhibitor), diuretics, aldosterone antagonist, ivabradine, devices (automatic implantable cardioverter defibrillator, cardiac resynchronisation therapy or both) and digoxin as a representation of treatments with strong evidence for their use in systolic heart failure. Treatment with omega-3 fatty acids, statins or anti-thrombotic therapies has limited benefits in a general heart failure population. Adoption of this mnemonic for current evidence-based treatments for heart failure may help improve prescribing rates and patient outcomes in this debilitating, high mortality condition. PMID:26109136

  16. Addition of Angiotensin Receptor Blockade or Mineralocorticoid Antagonism to Maximal Angiotensin-Converting Enzyme Inhibition in Diabetic Nephropathy

    Mehdi, Uzma F.; Adams-Huet, Beverley; Raskin, Philip; Vega, Gloria L.; Toto, Robert D.

    2009-01-01

    Aldosterone promotes glomerular and tubular sclerosis independent of angiotensin II in animal models of diabetic nephropathy. Most human studies testing the renoprotective benefit of adding an angiotensin receptor blocker or a mineralocorticoid receptor antagonist to a regimen based on inhibition of angiotensin-converting enzyme (ACE) used relatively low doses of ACE inhibitors. Furthermore, these studies did not determine whether antiproteinuric effects were independent of BP lowering. We co...

  17. Enzyme Hydrolysates from Stichopus horrens as a New Source for Angiotensin-Converting Enzyme Inhibitory Peptides

    Bita Forghani; Afshin Ebrahimpour; Jamilah Bakar; Azizah Abdul Hamid; Zaiton Hassan; Nazamid Saari

    2012-01-01

    Stichopus horrens flesh was explored as a potential source for generating peptides with angiotensin-converting enzyme (ACE) inhibitory capacity using 6 proteases, namely alcalase, flavourzyme, trypsin, papain, bromelain, and protamex. Degree of hydrolysis (DH) and peptide profiling (SDS-PAGE) of Stichopus horrens hydrolysates (SHHs) was also assessed. Alcalase hydrolysate showed the highest DH value (39.8%) followed by flavourzyme hydrolysate (32.7%). Overall, alcalase hydrolysate exhibited t...

  18. Preparation of lisinopril-capped gold nanoparticles for molecular imaging of angiotensin-converting enzyme

    Li, Yuan; Baeta, Cesar; Aras, Omer; Daniel, Marie-Christine

    2009-05-01

    Overexpression of angiotensin-converting enzyme (ACE) has been associated with the pathophysiology of cardiac and pulmonary fibrosis. Moreover, the prescription of ACE inhibitors, such as lisinopril, has shown a favorable effect on patient outcome for patients with heart failure or systemic hypertension. Thus targeted imaging of the ACE would be of crucial importance for monitoring tissue ACE activity as well as the treatment efficacy in heart failure. In this respect, lisinopril-coated gold nanoparticles were prepared to provide a new type of probe for targeted molecular imaging of ACE by tuned K-edge computed tomography (CT) imaging. The preparation involved non-modified lisinopril, using its primary amine group as the anchoring function on the gold nanoparticles surface. The stable lisinopril-coated gold nanoparticles obtained were characterized by UV-vis spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM). Their zeta potential was also measured in order to assess the charge density on the modified gold nanoparticles (GNPs).

  19. Effects of angiotensin-converting enzyme inhibitors and beta blockers on clinical outcomes in patients with and without coronary artery obstructions at angiography (from a Register-Based Cohort Study on Acute Coronary Syndromes).

    Manfrini, Olivia; Morrell, Christine; Das, Rajiv; Barth, Julian H; Hall, Alistair S; Gale, Christopher P; Cenko, Edina; Bugiardini, Raffaele

    2014-05-15

    We sought to determine the effectiveness of angiotensin-converting enzyme (ACE) inhibition and β-blocker treatment as a function of the degree of coronary artery disease (CAD) obstruction at angiography. The Evaluation of Methods and Management of Acute Coronary Events registry enrolled patients who had been hospitalized for an acute coronary syndrome. There were 1,602 patients who had cardiac catheterization that were used for this analysis. The main outcome measures were evidence-based therapies prescribed at discharge and 6-month incidence of all-cause mortality. The cohort consisted of 1,252 patients with obstructive CAD (>50% luminal diameter obstructed) and 350 patients with nonobstructive CAD. Multivariate logistic regression analysis adjusted for further medications and other clinical factors was performed. Patients with nonobstructive CAD had significantly (p <0.001) higher rates of β-blocker (77.8% vs 63.3%) and lower rates of ACE-inhibitor (57.7% vs 66.4%) prescriptions. In patients with nonobstructive CAD, ACE-inhibitor therapy was clearly associated with a lower 6-month mortality (odds ratio [OR] 0.31, 95% confidence interval [CI] 0.03 to 0.78, p = 0.004). No significant association between β-blocker use and death was found. In patients with obstructive CAD, both β blockers (OR 0.47, 95% CI 0.32 to 0.67, p <0.001) and ACE inhibitors (OR 0.47, 95% CI 0.26 to 0.87, p = 0.01) were significantly associated with a reduced risk of 6-month mortality. In conclusion, ACE-inhibitor therapy seems to be an effective first-line treatment for preventing the occurrence of mortality in patients with nonobstructive CAD. PMID:24698468

  20. Systemic vascular resistance during brief withdrawal of angiotensin converting enzyme inhibition in heart failure

    Gabrielsen, A; Bie, P; Christensen, N J;

    2002-01-01

    We tested the hypothesis that moderate increases in endogenous angiotensin II (Ang II) concentrations, induced by withdrawal of angiotensin converting enzyme inhibition (ACE-I) in patients with compensated heart failure (HF) on chronic medical therapy, do not increase or impair control of systemi...

  1. Angiotensin-converting enzyme activity and cognitive impairment during hypoglycaemia in healthy humans

    Pedersen-Bjergaard, Ulrik; Thomsen, Carsten E; Høgenhaven, Hans;

    2008-01-01

    INTRODUCTION: In type 1 diabetes increased risk of severe hypoglycaemia is associated with high angiotensin-converting enzyme (ACE) activity. We tested in healthy humans the hypothesis that this association is explained by the reduced ability of subjects with high ACE activity to maintain normal...

  2. Effect of angiotensin-converting enzyme inhibition on functional class in patients with left ventricular systolic dysfunction--a meta-analysis

    Abdulla, Jawdat; Pogue, Janice; Abildstrøm, Steen Z;

    2005-01-01

    BACKGROUND: The effect of angiotensin converting enzyme (ACE) inhibitors on symptoms in patients with left ventricular systolic dysfunction (LVSD) is controversial. AIMS: To perform a meta-analysis of studies evaluating effect of ACE inhibitors on New York Heart Association (NYHA) class in patien...

  3. A multi-center, double-blind, randomized, parallel group study to evaluate the effects of two different doses of losartan on morbidity and mortality in Chinese patients with symptomatic heart failure intolerant of angiotensin converting enzyme inhibitor t%A multi-center, double-blind, randomized, parallel group study to evaluate the effects of two different doses of losartan on morbidity and mortality in Chinese patients with symptomatic heart failure intolerant of angiotensin converting enzyme inhibitor treatment

    HU Da-yi; HUANG Jun; CAI Nai-sheng; ZHU Wen-ling; LI Yi-shi; Rachid Massaad; Mary E.Hanson; Kenneth Dickstein

    2012-01-01

    Background There have been no mortality/morbidity endpoint studies with losartan in Chinese heart failure patients.The objective was to evaluate the effects of high-dose vs.low-dose losartan on clinical outcomes in Chinese subjects with heart failure.Methods This study was a post hoc analysis of the Heart failure Endpoint evaluation of Angiotensin Ⅱ Antagonist losartan (HEAAL)trial (n=545).Chinese adults with symptomatic heart failure (New York Heart Association (NYHA) Ⅱ-Ⅳ)intolerant of treatment with angiotensin converting enzyme (ACE) inhibitors were randomized to losartan 150 mg or 50 mg daily.The primary endpoint was the composite event rate of all-cause death or hospitalization for heart failure.Safety and tolerability were assessed.Results Median follow-up was 4.8 years.Baseline characteristics were generally similar to the overall HEAAL cohort.Overall,120 (44.1%) subjects in the losartan 150 mg group and 137 (50.2%) subjects in the losartan 50 mg group died (any cause) or were hospitalized for heart failure (hazard ratio (OR) 0.807,95% CI0.631-1.031).There were no notable differences between treatment groups in the proportion of subjects with adverse experiences.Conclusion The results of this post hoc analysis in Chinese subjects,although not powered to show significance,were generally consistent with the main study results,which demonstrated a significantly reduced risk of all cause death or hospitalization for heart failure with daily losartan 150 mg vs.losartan 50 mg in subjects with symptomatic heart failure and intolerance to ACE inhibitors,supporting the use of the higher dose for optimum clinical benefit.

  4. Does the Angiotensin-converting enzyme (ACE gene insertion/deletion polymorphism modify the response to ACE inhibitor therapy? – A systematic review

    Perna Annalisa

    2005-10-01

    Full Text Available Abstract Background Pharmacogenetic testing to individualize ACE inhibitor therapy remains controversial. We conducted a systematic review to assess the effect modification of the insertion/deletion (I/D polymorphism of the ACE gene on any outcome in patients treated with ACE inhibitors for cardiovascular and/or renal disease. Methods Our systematic review involved searching six electronic databases, then contacting the investigators (and pharmaceutical industry representatives responsible for the creation of these databases. Two reviewers independently selected relevant randomized, placebo-controlled trials and abstracted from each study details on characteristics and quality. Results Eleven studies met our inclusion criteria. Despite repeated efforts to contact authors, only four of the eleven studies provided sufficient data to quantify the effect modification by genotypes. We observed a trend towards better response to ACE inhibitors in Caucasian DD carriers compared to II carriers, in terms of blood pressure, proteinuria, glomerular filtration rate, ACE activity and progression to end-stage renal failure. Pooling of the results was inappropriate, due to heterogeneity in ethnicity, clinical domains and outcomes. Conclusion Lack of sufficient genetic data from the reviewed studies precluded drawing any convincing conclusions. Better reporting of genetic data are needed to confirm our preliminary observations concerning better response to ACE inhibitors among Caucasian DD carriers as compared to II carriers.

  5. Individualised therapy of angiotensin converting enzyme (ACE) inhibitors in stable coronary artery disease: Overview of the primary results of the PERindopril GENEtic association (PERGENE) study

    J.J. Brugts (Jasper); M.P.M. de Maat (Moniek); A.H.J. Danser (Jan); H. Boersma (Eric); M.L. Simoons (Maarten)

    2012-01-01

    textabstractIn patients with stable coronary artery disease (CAD) without overt heart failure, ACE inhibitors are among the most commonly used drugs as these agents have been proven effective in reducing the risk of cardiovascular events. Considerable individual variations in the blood pressure resp

  6. 血管紧张素转化酶抑制剂在冠心病治疗中的应用%Application of angiotensin-converting enzyme inhibitors in coronary artery disease

    周艳丽; 李新立

    2013-01-01

    This article summarizes the outcomes of clinical trials and the Chinese newest guidelines for management of patients with acute ST-segment elevation myocardial infarction published in 2010, the Chinese newest guidelines for management of patients with non-ST-segment elevation acute coronary syndrome published in 2012, and the Chinese newest guidelines for management of patients with stable angina published in 2007 and the application of the angiotensin-converting enzyme inhibitors in coronary artery diseases including acute ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction and stable angina, with focus on the current status in China.%本文以临床试验和中国2010年发表的《急性ST段抬高型心肌梗死诊断和治疗指南》、2012年发表的《非ST段抬高的急性冠脉综合征诊断和治疗指南》和2007年发表的《稳定型心绞痛诊断与治疗指南》为依据,从急性ST段抬高型心肌梗死、非ST段抬高的心肌梗死和稳定型心绞痛3个方面来概述血管紧张素转化酶抑制剂在冠心病治疗中的应用,同时通过一项调查研究给出此类药物在我国冠心病患者中的应用现况。

  7. Do Angiotensin-Converting Enzyme Inhibitors Reduce the Risk of Symptomatic Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer After Definitive Radiation Therapy? Analysis of a Single-Institution Database

    Wang, Hongmei [Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, P.R. of China (China); Liao, Zhongxing, E-mail: zliao@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhuang, Yan; Xu, Ting; Nguyen, Quynh-Nhu; Levy, Lawrence B.; O' Reilly, Michael [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gold, Kathryn A. [Department of Thoracic Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gomez, Daniel R. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-12-01

    Purpose: Preclinical studies have suggested that angiotensin-converting enzyme inhibitors (ACEIs) can mitigate radiation-induced lung injury. We sought here to investigate possible associations between ACEI use and the risk of symptomatic radiation pneumonitis (RP) among patients undergoing radiation therapy (RT) for non–small cell lung cancer (NSCLC). Methods and Materials: We retrospectively identified patients who received definitive radiation therapy for stages I to III NSCLC between 2004 and 2010 at a single tertiary cancer center. Patients must have received a radiation dose of at least 60 Gy for a single primary lung tumor and have had imaging and dosimetric data available for analysis. RP was quantified according to Common Terminology Criteria for Adverse Events, version 3.0. A Cox proportional hazard model was used to assess potential associations between ACEI use and risk of symptomatic RP. Results: Of 413 patients analyzed, 65 were using ACEIs during RT. In univariate analysis, the rate of RP grade ≥2 seemed lower in ACEI users than in nonusers (34% vs 46%), but this apparent difference was not statistically significant (P=.06). In multivariate analysis of all patients, ACEI use was not associated with the risk of symptomatic RP (hazard ratio [HR] = 0.66; P=.07) after adjustment for sex, smoking status, mean lung dose (MLD), and concurrent carboplatin and paclitaxel chemotherapy. Subgroup analysis showed that ACEI use did have a protective effect from RP grade ≥2 among patients who received a low (≤20-Gy) MLD (P<.01) or were male (P=.04). Conclusions: A trend toward reduction in symptomatic RP among patients taking ACEIs during RT for NSCLC was not statistically significant on univariate or multivariate analyses, although certain subgroups may benefit from use (ie, male patients and those receiving low MLD). The evidence at this point is insufficient to establish whether the use of ACEIs does or does not reduce the risk of RP.

  8. Angiotensin converting enzyme 2 (ACE2) activity in fetal calf serum: implications for cell culture research

    Lubel, J. S.; Herath, C. B.; Velkoska, E.; Casley, D. J.; Burrell, L. M.; Angus, P. W.

    2008-01-01

    Cell culture experiments often employ the use of culture media that contain fetal calf serum (FCS). The angiotensin peptides angiotensin II and angiotensin 1–7 have opposing effects with angiotensin converting enzyme 2 (ACE2) being the enzyme predominantly responsible for generating angiotensin 1–7 from angiotensin II. The effect of FCS on angiotensin peptides has not previously been described. We have shown that FCS has ACE2 enzyme activity capable of degrading angiotensin II and generating ...

  9. A RETROSPECTIVE STUDY ON THE POTENTIAL DRUG INTERACTION BETWEEN ANGIOTENSIN CONVERTING ENZYME INHIBITOR OR ANGIOTENSIN RECEPTOR ANTAGONIST AND OTHER DRUGS IN END-STAGE CHRONIC RENAL FAILURE PATIENTS

    Honey Iskandar

    2012-10-01

    Full Text Available Increasing number of chronic renal failure (CRF patients had reflected an increase in the number of patients with diabetes and hypertension. Therefore, health practitioners would be faced with management of complicated medical problems for the patients of chronic renal disease. In this way, various complications of chronic renal failure would lead to polypharmacy, where the patients receive three to five drugs in a dose. Development of polypharmacy had made the potential of drug interaction greater. The objective was to determine whether CRF patients admitted to hospital with specific adverse drug reactions were likely to have been prescribed with interacting drugs. Retrospective study was designed. The study was conducted at the General Practice Rooms Floor 1 – Floor VI of Central Army Hospital Gatot Soebroto Jakarta. The study was conducted from December 2011 – February 2012. The data were collected in a retrospective way for a year (January – December 2011. End-stage CRF patients who were having hemodialysis therapy and receiving ACE Inhibitor drugs or Angiotensin II Receptor Antagonist (AIIRA and receiving treatment at the General Practice Rooms at Central Army Hospital Gatot Soebroto Jakarta. During the period of January – December 2011, 84 patients were treated with end-stage CRF at the Central Army Hospital and having routine hemodialysis and 44 patients were receiving therapy with ACE Inhibitor and AIIRA. Other drugs simultaneously given with ACE Inhibitor and AIIRA were captopril-spironolactone, captopril-aspirin, captopril-allopurinol, captopril-KSR, captopril-furosemide, lisinopril-furosemide and valsartan-mefenemic acid. An increase in adverse effects of the drugs was found based on the clinical evaluation and laboratory examination. The adverse effects included hyperkalemia (9,09%, decrease in anti-hypertension effect (6,8%, acute hypotension (40%, and declining renal function (11,36%. The study identifies drug interaction

  10. A Crucial Role in Fertility for the Oyster Angiotensin-Converting Enzyme Orthologue CgACE

    Riviere, Guillaume; Fellous, Alexandre; Franco, Alban; Bernay, Benoit; Favrel, Pascal

    2011-01-01

    Angiotensin-converting enzyme (ACE) is a highly conserved metallopeptidase. In mammals, the somatic isoform governs blood pressure whereas the germinal isoform (tACE) is required for fertility. In Ecdysozoans, ACE-like enzymes are implicated in reproduction. Despite ACE orthologues being present from bacteria to humans, their function(s) remain(s) unknown in distant organisms such as Lophotrochozoans. In silico analysis of an oyster (Crassostrea gigas) EST library suggested the presence of an...

  11. Why is plasma angiotensin-converting enzyme activity elevated in hyperthyroidism?

    Roulston, J. E.; Gold, A; Wright, M.; Walker, S. W.

    1987-01-01

    The elevation in plasma angiotensin-converting enzyme (ACE) levels observed in patients with hyperthyroidism is unexplained. In this study three hypotheses were investigated. Results from a study using rats treated with thyroid hormones indicated that the increased ACE was not due to increased cleavages of enzyme from lung endothelia. Data from patients with specific tissue damage argue against a nonspecific release of ACE from damaged cells. Data from cultured cell experiments, however, stro...

  12. Angiotensin converting enzyme gene polymorphism in familial hypertrophic cardiomyopathy patients

    Yu, B; Peric, S.; Ross, D. [Royal Prince Alfred Hospital, Campertown (Australia)] [and others

    1994-09-01

    An insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme (ACE) gene is a useful predictor of human plasma ACE levels. ACE levels tend to be lowest in subjects with ACE genotype DD and intermediate in subjects with ACE genotype ID. Angiotensin II (Ang II) as a product of ACE is a cardiac growth factor and produces a marked hypertrophy of the chick myocyte in cell culture. Rat experiments also suggest that a small dose of ACE inhibitor that does not affect the afterload results in prevention or regression of cardiac hypertrophy. In order to study the relationship of ACE and the severity of hypertrophy, the ACE genotype has been determined in 28 patients with a clinical diagnosis of familial hypertrophic cardiomyopathy (FHC) and 51 normal subjects. The respective frequencies of I and D alleles were: 0.52 and 0.48 (in FHC patients) and 0.44 and 0.56 (in the normal controls). There was no significant difference in the allele frequencies between FHC and normal subjects ({chi}{sup 2}=0.023, p>0.05). The II, ID, and DD genotypes were present in 7, 15, and 6 FHC patients, respectively. The averages of maximal thickness of the interventricular septum measured by echocardiography or at autopsy were 18 {plus_minus}3, 19{plus_minus}4, and 19{plus_minus}3 mm in II, ID and DD genotypes, respectively. The ACE gene polymorphism did not correlate with the severity of left ventricular hypertrophy in FHC patients (r{sub s}=0.231, p>0.05). These results do not necessarily exclude the possible effect of Ang II on the hypertrophy since the latter may be produced through the action of chymase in the human ventricles. However, ACE gene polymorphism is not a useful predictor of the severity of myocardial hypertrophy in FHC patients.

  13. Angiotensin converting enzyme and memory: preclinical and clinical data.

    Sudilovsky, A; Turnbull, B; Croog, S H; Crook, T

    Results from both preclinical and clinical studies described here suggest that ACE may have a role in the modulation of cognitive memory processes in the rat and in humans. The finding of improved cognitive performance among patients treated with captopril relative to those treated with propranolol or methyldopa is consistent with other clinical and prec-clinical data. Clinical data derive primarily from quality of life measures based on interviews with patients in the same clinical trial from which our other cognitive data are drawn. For example, mental acuity in the workplace was reported to have improved significantly from baseline to week 24 in patients on captopril (p less than 0.05), although it did not change in patients treated with propranolol and worsened in those receiving methyldopa (Croog et al, 1987). The difference between captopril and methyldopa was significant (p less than 0.01). Pre-clinical data come primarily from studies demonstrating that inhibitors of ACE delay CAE in rats when compared not only with methyldopa, but also with saline (Sudilovsky et al, 1984, 1986). A fundamental question is how could inhibition of ACE improve cognitive functioning independent of blood pressure control. It is known that captopril exerts its antihypertensive effects primarily through inhibition of the ACE and that this is present in the brain as well as in non-neuronal tissues elsewhere (Ganten et al, 1982; Strittmatter et al, 1983, 1984). The activity of the enzyme has been found to be significantly increased in the caudate nucleus, the frontal cortex, parahyppocampal gyrus, and medial hippocampus of patients dying with Alzheimer's disease when compared to age-matched controls (Arregui et al, 1982). In addition, AII has been shown to impair performance on various learning and memory paradigms in animals (Melo and Graeff, 1975; Morgan and Routtenberg, 1977). Raising the level of endogenous AII by intravenous administration of its precursor renin has similar

  14. Drying Technology of Angiotensin Converting Enzyme Inhibitory Peptide Derived from Bovine Casein

    JIANG Zhanmei; Hue Guicheng; TIAN Be

    2009-01-01

    Drying technology of angiotensin converting enzyme (ACE) inhibitory peptides derived from bovine casein was investigated. No significance was observed on ACE inhibitory activity of products prepared by spay drying and freeze drying (P>0.05). Spay drying was the best drying process for practical industry production. The inlet temperature ranged from 140℃ to 160℃ and the exit temperature ranged from 70℃ to 90℃ during the spay drying process. Under the optimal eonditious, scale-up of angiotensin converted enzyme inhibitory peptide from 1 L to 10 L and the experiment was successively conducted. Peptide yield was 29% and half inhibitory concentration(IC50) was 0.53g·L-1.

  15. Angiotensin-converting enzyme: an indicator of bleomycin-induced pulmonary toxicity in humans?

    Sørensen, Peter G; Rømer, F K; Cortes, Dina

    1984-01-01

    In order to evaluate bleomycin-associated lung damage in humans, lung function parameters and serum levels of the endothelial-bound angiotensin-converting enzyme (ACE) were determined by serial measurements in 11 patients who were treated for testicular cancer. None developed clinical or radiolog......In order to evaluate bleomycin-associated lung damage in humans, lung function parameters and serum levels of the endothelial-bound angiotensin-converting enzyme (ACE) were determined by serial measurements in 11 patients who were treated for testicular cancer. None developed clinical or...... radiological evidence of pulmonary damage. While the static and dynamic lung function parameters were unchanged, carbon monoxide diffusion capacity (DLCO) decreased significantly (P less than 0.01) during a total of 126 days of pulsed regimen, indicating damage to the alveolar-endothelial membrane. S-ACE was...

  16. Targeted Catalytic Inactivation of Angiotensin Converting Enzyme by Lisinopril-Coupled Transition Metal Chelates

    Joyner, Jeff C.; Hocharoen, Lalintip; Cowan, J. A.

    2012-01-01

    A series of compounds that target reactive transition metal chelates to somatic Angiotensin Converting Enzyme (sACE-1) have been synthesized. Half maximal inhibitory concentrations (IC50) and rate constants for both inactivation and cleavage of full length sACE-1 have been determined and evaluated in terms of metal-chelate size, charge, reduction potential, coordination unsaturation, and coreactant selectivity. Ethylenediamine-tetraacetic acid (EDTA), nitrilotriacetic acid (NTA), 1,4,7,10-tet...

  17. A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme

    Bernstein, Kenneth E.; Ong, Frank S.; Blackwell, Wendell-Lamar B.; Shah, Kandarp H.; Giani, Jorge F.; Gonzalez-Villalobos, Romer A.; Shen, Xiao Z.; Fuchs, Sebastien

    2013-01-01

    Angiotensin-converting enzyme (ACE) is a zinc-dependent peptidase responsible for converting angiotensin I into the vasoconstrictor angiotensin II. However, ACE is a relatively nonspecific peptidase that is capable of cleaving a wide range of substrates. Because of this, ACE and its peptide substrates and products affect many physiologic processes, including blood pressure control, hematopoiesis, reproduction, renal development, renal function, and the immune response. The defining feature of...

  18. Inhibition of Angiotensin-Converting Enzyme Activity by Flavonoids: Structure-Activity Relationship Studies

    Ligia Guerrero; Julián Castillo; Mar Quiñones; Santiago Garcia-Vallvé; Lluis Arola; Gerard Pujadas; Begoña Muguerza

    2012-01-01

    Previous studies have demonstrated that certain flavonoids can have an inhibitory effect on angiotensin-converting enzyme (ACE) activity, which plays a key role in the regulation of arterial blood pressure. In the present study, 17 flavonoids belonging to five structural subtypes were evaluated in vitro for their ability to inhibit ACE in order to establish the structural basis of their bioactivity. The ACE inhibitory (ACEI) activity of these 17 flavonoids was determined by fluorimetric metho...

  19. Post-exercise reduction in blood pressure in hypertensive subjects: effects of angiotensin converting enzyme inhibition.

    Beaulieu, M.; Nadeau, A.; Lacourcière, Y; Cléroux, J

    1993-01-01

    1. Much attention has been given to the effects of various classes of antihypertensive drugs on blood pressure and haemodynamics. The effects of a single bout of exercise on post-exercise blood pressure have also been studied by several investigators. However, the combined effects of prior exercise and antihypertensive medication has drawn less attention. 2. We examined the separate and combined effects of a single bout of exercise and of angiotensin converting enzyme (ACE) inhibition with a ...

  20. Angiotensin-converting enzyme gene and retinal arteriolar narrowing: The Funagata Study

    Tanabe, Y; Kawasaki, R.; J. J. Wang; Wong, T Y; Mitchell, P; Daimon, M; Oizumi, T; Kato, T.; Kawata, S.; Kayama, T; Yamashita, H.

    2009-01-01

    The purpose of this study is to determine whether the angiotensin-converting enzyme (ACE) gene polymorphism is associated with retinal arteriolar narrowing, a subclinical marker of chronic hypertension. The Funagata Study examined a population-based sample of Japanese aged 35+ years; 368 participants had both retinal vessel diameter measurements and ACE insertion/deletion (ACE I/D) polymorphism analyses performed. Assessment of retinal vessel diameter and retinal vessel wall signs followed th...

  1. The angiotensin-converting enzyme (ACE) gene family of Anopheles gambiae.

    Isaac R Elwyn; Lee Alison J; Smith Judith A; Burnham Susan; Shirras Alan D

    2005-01-01

    Abstract Background Members of the M2 family of peptidases, related to mammalian angiotensin converting enzyme (ACE), play important roles in regulating a number of physiological processes. As more invertebrate genomes are sequenced, there is increasing evidence of a variety of M2 peptidase genes, even within a single species. The function of these ACE-like proteins is largely unknown. Sequencing of the A. gambiae genome has revealed a number of ACE-like genes but probable errors in the Ensem...

  2. Release of angiotensin converting enzyme-inhibitor peptides during in vitro gastrointestinal digestion of Parmigiano Reggiano PDO cheese and their absorption through an in vitro model of intestinal epithelium.

    Basiricò, L; Catalani, E; Morera, P; Cattaneo, S; Stuknytė, M; Bernabucci, U; De Noni, I; Nardone, A

    2015-11-01

    The occurrence of 8 bovine casein-derived peptides (VPP, IPP, RYLGY, RYLG, AYFYPEL, AYFYPE, LHLPLP, and HLPLP) reported as angiotensin converting enzyme-inhibitors (ACE-I) was investigated in the 3-kDa ultrafiltered water-soluble extract (WSE) of Parmigiano Reggiano (PR) cheese samples by ultra-performance liquid chromatography coupled to high-resolution mass spectrometry via an electrospray ionization source. Only VPP, IPP, LHLPLP, and HLPLP were revealed in the WSE, and their total amount was in the range of 8.46 to 21.55 mg/kg of cheese. Following in vitro static gastrointestinal digestion, the same ACE-I peptides along with the newly formed AYFYPEL and AYFYPE were found in the 3 kDa WSE of PR digestates. Digestates presented high amounts (1,880-3,053 mg/kg) of LHLPLP, whereas the remaining peptides accounted for 69.24 to 82.82 mg/kg. The half-maximal inhibitory concentration (IC50) values decreased from 7.92 ± 2.08 in undigested cheese to 3.20 ± 1.69 after in vitro gastrointestinal digestion. The 3-kDa WSE of digested cheeses were used to study the transport of the 8 ACE-I peptides across the monolayers of the Caco-2 cell culture grown on a semipermeable membrane of the transwells. After 1h of incubation, 649.20 ± 148.85 mg/kg of LHLPLP remained in the apical compartment, whereas VPP, IPP, AYFYPEL, AYFYPE, and HLPLP accounted in total for less than 36.78 mg/kg. On average, 0.6% of LHLPLP initially present in the digestates added to the apical compartment were transported intact to the basolateral chamber after the same incubation time. Higher transport rate (2.9%) was ascertained for the peptide HLPLP. No other intact ACE-I peptides were revealed in the basolateral compartment. For the first time, these results demonstrated that the ACE-I peptides HLPLP and LHLPLP present in the in vitro digestates of PR cheese are partially absorbed through an in vitro model of human intestinal epithelium. PMID:26364103

  3. Chinese medicinal formula Fufang Xueshuantong capsule could inhibit the activity of angiotensin converting enzyme

    Sheng, Shujing; Wang, Yonggang; Long, Chaofeng; Su, Weiwei; Rong, Xia

    2014-01-01

    Fufang Xueshuantong (FXST) capsule, a Chinese medicinal formula composed of four herbals – Panax notoginseng, Radix Astragali, Radix Salvia Miltiorrhizae and Radix Scrophulariaceae, has been used to treat cardiovascular diseases for many years, but the pharmacological mechanisms underlying its effects has not been clarified. This study investigates if a connection between FXST and angiotensin converting enzyme (ACE) might be an explanation for its pharmacological effects. ACE inhibition assay was performed on FXST capsule, 50% ethanol extracts from the four herbals and three selected saponins most abundant in P. notoginseng (Ginsenoside Rg1, Ginsenoside Rb1 and Notoginsenoside R1) using a biochemical test. Reversed-phase high-performance liquid chromatography of liberated hippuric acid from the ACE assay was conducted to determine the inhibitory effect. As a result, FXST and extracts from P. notoginseng showed a significant and dose-dependent inhibition on ACE activity with the IC50 values of 115 μg/ml and 179 μg/ml, respectively. But extracts from the other three herbals and the three selected saponins had no significant effect on ACE inhibition. Compared to other reported plant extracts, FXST could be considered as an effective ACE inhibitor. The inhibition of ACE activity supports the traditional use of FXST on blood circulation and the inhibitory property of FXST is mainly caused by P. notoginseng. PMID:26019516

  4. Elevated serum angiotensin converting enzyme levels in metastatic ovarian dysgerminoma.

    Cotter, T P

    2012-02-03

    A case of a 32-year-old XY genotype female is described, presenting with mediastinal and abdominal lymphadenopathy and associated with an elevated serum angiotensin I converting enzyme (SACE) level. Lymph node histology showed a malignant dysgerminoma of ovarian origin. Combined chemotherapy led to a radiological regression of the lymphadenopathy and coincided with a decrease in SACE concentration. The authors suggest that SACE may be a marker for disseminated germinoma tumours and may be useful for monitoring treatment.

  5. A crucial role in fertility for the oyster angiotensin-converting enzyme orthologue CgACE.

    Riviere, Guillaume; Fellous, Alexandre; Franco, Alban; Bernay, Benoit; Favrel, Pascal

    2011-01-01

    Angiotensin-converting enzyme (ACE) is a highly conserved metallopeptidase. In mammals, the somatic isoform governs blood pressure whereas the germinal isoform (tACE) is required for fertility. In Ecdysozoans, ACE-like enzymes are implicated in reproduction. Despite ACE orthologues being present from bacteria to humans, their function(s) remain(s) unknown in distant organisms such as Lophotrochozoans. In silico analysis of an oyster (Crassostrea gigas) EST library suggested the presence of an ACE orthologue in molluscs. Primer walking and 5'-RACE revealed that the 1.9 kb cDNA encodes CgACE, a 632 amino acid protein displaying a conserved single active site and a putative C-terminal transmembrane anchor, thus resembling human tACE, as supported by molecular modelling. FRET activity assays and Maldi-TOF spectrometry indicated that CgACE is a functional dipeptidyl-carboxypeptidase which is active on Angiotensin I and sensitive to ACE inhibitors and chloride ion concentration. Immunocytochemistry revealed that, as its human counterpart, recombinant CgACE is synthesised as a transmembrane enzyme. RT-qPCR, in-situ hybridization and immunohistochemistry shed light on a tissue, and development stage, specific expression pattern for CgACE, which is increased in the gonad during spermatogenesis. The use of ACE inhibitors in vivo indicates that the dipeptidase activity of CgACE is crucial for the oyster fertilization. Our study demonstrates that a transmembrane active ACE is present in the oyster Crassostrea gigas, and for the first time ascribes a functional role for ACE in Lophotrochozoans. Its biological function in reproduction is conserved from molluscs to humans, a finding of particular evolutionary interest especially since oysters represent the most important aquaculture resource worldwide. PMID:22174750

  6. A crucial role in fertility for the oyster angiotensin-converting enzyme orthologue CgACE.

    Guillaume Riviere

    Full Text Available Angiotensin-converting enzyme (ACE is a highly conserved metallopeptidase. In mammals, the somatic isoform governs blood pressure whereas the germinal isoform (tACE is required for fertility. In Ecdysozoans, ACE-like enzymes are implicated in reproduction. Despite ACE orthologues being present from bacteria to humans, their function(s remain(s unknown in distant organisms such as Lophotrochozoans. In silico analysis of an oyster (Crassostrea gigas EST library suggested the presence of an ACE orthologue in molluscs. Primer walking and 5'-RACE revealed that the 1.9 kb cDNA encodes CgACE, a 632 amino acid protein displaying a conserved single active site and a putative C-terminal transmembrane anchor, thus resembling human tACE, as supported by molecular modelling. FRET activity assays and Maldi-TOF spectrometry indicated that CgACE is a functional dipeptidyl-carboxypeptidase which is active on Angiotensin I and sensitive to ACE inhibitors and chloride ion concentration. Immunocytochemistry revealed that, as its human counterpart, recombinant CgACE is synthesised as a transmembrane enzyme. RT-qPCR, in-situ hybridization and immunohistochemistry shed light on a tissue, and development stage, specific expression pattern for CgACE, which is increased in the gonad during spermatogenesis. The use of ACE inhibitors in vivo indicates that the dipeptidase activity of CgACE is crucial for the oyster fertilization. Our study demonstrates that a transmembrane active ACE is present in the oyster Crassostrea gigas, and for the first time ascribes a functional role for ACE in Lophotrochozoans. Its biological function in reproduction is conserved from molluscs to humans, a finding of particular evolutionary interest especially since oysters represent the most important aquaculture resource worldwide.

  7. QM/MM investigation of the catalytic mechanism of angiotensin-converting enzyme.

    Mu, Xia; Zhang, Chunchun; Xu, Dingguo

    2016-06-01

    Angiotensin-converting enzyme (ACE) converts angiotensin I to angiotensin II and degrades bradykinin and other vasoactive peptides. ACE inhibitors are used to treat diseases such as hypertension and heart failure. It is thus highly desirable to understand the catalytic mechanism of ACE, as this should facilitate the design of more powerful and selective ACE inhibitors. ACE exhibits two different active domains, the C-domain and the N-domain. In this work, we systematically investigated the inhibitor- and substrate-binding patterns in the N-domain of human ACE using a combined quantum mechanical and molecular mechanical approach. The hydrolysis of hippuryl-histidyl-leucine (HHL) as catalyzed by the N-domain of human somatic ACE was explored, and the effects of chloride ion on the overall reaction were also investigated. Two models, one with and one without a chloride ion at the first binding position, were then designed to examine the chloride dependence of inhibitor-substrate binding and the catalytic mechanism. Our calculations indicate that the hydrolysis reaction follows a stepwise general base/general acid catalysis path. The estimated mean free energy barrier height in the two models is about 15.6 kcal/mol, which agrees very well with the experimentally estimated value of 15.8 kcal/mol. Our simulations thus suggest that the N-domain is in a mixed form during ACE-catalyzed hydrolysis, with the single-chloride-ion and the double-chloride-ion forms existing simultaneously. Graphical Abstract Superposition of ACE C- and N- domains. PMID:27184002

  8. The Functional Angiotensin Converting Enzyme Gene I/D Polymorphism Does not Alter Susceptibility to Chronic Pancreatitis

    Whitcomb DC

    2004-11-01

    Full Text Available CONTEXT: Alterations of the renin-angiotensin system have been implicated in the pathogenesis of various diseases. The angiotensin converting enzyme is a key enzyme in the renin-angiotensin system. A deletion polymorphism of a 287-bp fragment of intron 16 of the angiotensin converting enzyme gene allele results in higher levels of circulating enzyme. ACE deletion genotype has been linked to heart diseases, sarcoidosis and liver fibrosis. The pancreatic renin-angiotensin system plays a role in the development of pancreatic fibrosis and ACE inhibitors decrease pancreatic fibrosis in experimental models. OBJECTIVES: We investigated the frequency of the ACE gene insertion/deletion polymorphism in chronic pancreatitis patients and controls. PATIENTS: Subjects with familial pancreatitis (n=51, sporadic chronic pancreatitis (n=104, and healthy controls (n=163 were evaluated. MAIN OUTCOME MEASURE: The presence of ACE insertion/deletion polymorphism. RESULTS: The frequency of the ACE gene deletion allele was similar in familial pancreatitis (49.0% sporadic pancreatitis (51.0% and controls (55.8%. Furthermore, there was no significant difference in clinical features between patients with ACE-insertion or insertion/deletion genotypes vs. patients with ACE-deletion genotype. CONCLUSION: We conclude that the ACE deletion genotype does not make a significant contribution to the pathogenesis and the progression of chronic pancreatitis.

  9. Development of a Spectrophotometric Method for Monitoring Angiotensin-Converting Enzyme in Dairy Products

    Julijana Tomovska*, S. Presilski, N. Gjorgievski, N. Tomovska1, M. S. Qureshi2 and N. P. Bozinovska3

    2013-01-01

    Full Text Available The angiotensin-converting enzyme (ACE regulates the levels of blood pressure through generation of angiotensin-II from angiotensin-I. It is of great importance to have a reliable and yet simple method for a quantitative determination ACE inhibitory peptides in whey of milk products. A rapid, simple, sensitive and accurate spectrophotometric kinetic method has been developed for determination of ACE inhibitory peptides, using competitive inhibition. Samples of dairy product from the market were used for the determination of ACE inhibitory peptides in whey. Holmquist’s kinetic method was used for determining ACE inhibitory activity in blood serum and Ronca-Testoni method was used for the determination of ACE inhibitory activity in whey. Enzymatic inhibition activity was determined using 0.8 mmol/L FAPGG (N-[3-(Furyl –Acryloyl]-L-Phenylalanyl Glycyl Glycyne as the substrate in 50 mmol/L Tris buffer at pH 8.2 at 37°C and a standard serum containing ACE. First, a solution of whey was mixed in a 1 to 10 ratio with serum (elevation containing high ACE activity. The enzymatic activity was determined by monitoring the decrease in absorbance at 340 nm as result of hydrolysis of the substrate. The concentration of ACE inhibitory peptides was determined from a standard curve of inhibitor concentration versus percent of ACE inhibition. The study suggests that the method possesses good reproducibility and accuracy. The linear range enabled determination of high enzymatic activity of ACE and all ACE inhibitory peptides from dairy products act as competitive inhibitors.

  10. Different in vivo functions of the two catalytic domains of angiotensin converting enzyme (ACE)

    Bernstein, Kenneth E.; Shen, Xiao Z.; Gonzalez-Villalobos, Romer A.; Billet, Sandrine; Okwan-Duodu, Derick; Ong, Frank S.; Fuchs, Sebastien

    2010-01-01

    Angiotensin converting enzyme (ACE) can cleave angiotensin I, bradykinin, neurotensin and many other peptide substrates in vitro. In part, this is due to the structure of ACE, a protein composed of two independent catalytic domains. Until very recently, little was known regarding the specific in vivo role of each ACE domain, and they were commonly regarded as equivalent. This is not true, as shown by mouse models with a genetic inactivation of either the ACE N- or C-domains. In vivo, most ang...

  11. Pharmacophore-based structure optimization of angiotensin converting enzyme inhibitory peptide

    WANG Wei; SHEN ShengRong; FENG FengQin; HE GuoQing; WANG ZhanLi

    2008-01-01

    Chemical feature based pharmacophore models were generated for an angiotensin converting enzyme (ACE) inhibitory peptide using the Discovery Studio 2.0 pharmacophore modeling approach. The pharmacophore hypothesis selected has five features (one negative lonizable region, one hydrogen bond donor, one hydrogen bond acceptor and two hydrophobic functional groups). Additionally, ACE inhibitory hexapeptide previously obtained from silkworm pupae protein was optimized to target the ACE based on the selected pharmacophore. The results suggest that tri-peptide (thr-val-phe) may be structural determinant of ACE activity. Docking studies further provided confidence for the validity of the selected pharmacophore model to perform structure optimization of the ACE inhibitory peptide.

  12. Angiotensin-converting enzyme (ACE-I/D) polymorphism frequency in Brazilian soccer players.

    Coelho, Daniel Barbosa; Pimenta, Eduardo; Rosse, Izinara Cruz; Veneroso, Christiano; Pussieldi, Guilherme; Becker, Lenice Kapes; Carvalho, Maria-Raquel; Silami-Garcia, Emerson

    2016-06-01

    This study aimed to analyze the angiotensin-converting enzyme (ACE-I/D) allelic and genotypic frequencies in Brazilian soccer players of different ages. The study group comprised 353 players from first-division clubs in the under (U)-14, U-15, U-17, U-20, and professional categories. The allelic and genotypic frequencies did not differ significantly in any of the categories between the group of players and the control group. This was the first study of ACE-I/D polymorphism in Brazilian soccer players. PMID:27232187

  13. Effects of altered ventilatory patterns of rabbit pulmonary endothelial angiotensin converting enzyme function, in vivo

    Because alveolar pressure can influence pulmonary blood flow, volume and surface area, the authors have studied the effects of airway pressure on endothelial angiotensin converting enzyme (ACE) function in rabbit lungs in vivo, utilizing indicator dilution techniques with 3H-Benzoyl-Phe-Ala-Pro (BPAP) as substate. Static inclation of the lungs to a pressure of 0 or 5 mmHg did not change percent transpulmonary metabolism and Amax/Km ratio in comparison to control measurements during conventional mechanical ventilation. When the inflation pressure was increased to 10 mmHg, percent metabolism of 3H-BPAP remained unaltered but Amax/Km decreased over 40% from control. This decrease was in close relation to the reduction in pulmonary blood flow. Addition of 5 cm H2O positive end-expiratory pressure (PEEP) to the mechanical ventilation also decreased Amax/Km values and pulmonary blood flow but did not influence percent metabolism of 3H-BPAP. These results suggest that the detected alterations in ACE kinetics were more likely due to hemodynamic changes than enzyme dysfunction. The authors propose that high static alveolar pressures as well as PEEP did not affect angiotensin converting enzyme function, but reduced the fraction of perfused microvessels reflected in changes in Amax/Km ratios

  14. Intrarenal distributions and changes of Angiotensin-converting enzyme and Angiotensin-converting enzyme 2 in feline and canine chronic kidney disease.

    Mitani, Sawane; Yabuki, Akira; Sawa, Mariko; Chang, Hye-Sook; Yamato, Osamu

    2014-01-01

    Angiotensin-converting enzyme (ACE) is a key enzyme in the renin-angiotensin system (RAS). ACE2 is a newly identified member of the RAS. The present immunohistochemical study focused on changes in intrarenal ACE and ACE2 immunoreactivity in feline and canine chronic kidney disease (CKD). ACE immunoreactivity was predominantly observed in the brush border of the proximal tubules in dogs and cats. ACE immunoreactivity was lower in CKD kidneys than in normal kidneys, and quantitative analysis demonstrated negative correlations between ACE and renal tissue damage in dogs. ACE2 immunoreactivity was also detected in the proximal tubules; it increased or decreased with CKD in dogs, depending on the renal region assessed. The changes in ACE and ACE2 in CKD were associated with the plasma creatinine concentration in dogs. Findings from dogs with glomerulonephritis were similar to those from dogs with non-glomerulonephritis. The present study suggests that changes in the intrarenal expression of ACE and ACE2 contribute to the pathological mechanisms of canine CKD, but not to the mechanisms of feline CKD. PMID:24004970

  15. Top-down Targeted Metabolomics Reveals a Sulfur-Containing Metabolite with Inhibitory Activity against Angiotensin-Converting Enzyme in Asparagus officinalis.

    Nakabayashi, Ryo; Yang, Zhigang; Nishizawa, Tomoko; Mori, Tetsuya; Saito, Kazuki

    2015-05-22

    The discovery of bioactive natural compounds containing sulfur, which is crucial for inhibitory activity against angiotensin-converting enzyme (ACE), is a challenging task in metabolomics. Herein, a new S-containing metabolite, asparaptine (1), was discovered in the spears of Asparagus officinalis by targeted metabolomics using mass spectrometry for S-containing metabolites. The contribution ratio (2.2%) to the IC50 value in the crude extract showed that asparaptine (1) is a new ACE inhibitor. PMID:25922884

  16. Enzyme Hydrolysates from Stichopus horrens as a New Source for Angiotensin-Converting Enzyme Inhibitory Peptides

    Bita Forghani

    2012-01-01

    Full Text Available Stichopus horrens flesh was explored as a potential source for generating peptides with angiotensin-converting enzyme (ACE inhibitory capacity using 6 proteases, namely alcalase, flavourzyme, trypsin, papain, bromelain, and protamex. Degree of hydrolysis (DH and peptide profiling (SDS-PAGE of Stichopus horrens hydrolysates (SHHs was also assessed. Alcalase hydrolysate showed the highest DH value (39.8% followed by flavourzyme hydrolysate (32.7%. Overall, alcalase hydrolysate exhibited the highest ACE inhibitory activity (IC50 value of 0.41 mg/mL followed by flavourzyme hydrolysate (IC50 value of 2.24 mg/mL, trypsin hydrolysate (IC50 value of 2.28 mg/mL, papain hydrolysate (IC50 value of 2.48 mg/mL, bromelain hydrolysate (IC50 value of 4.21 mg/mL, and protamex hydrolysate (IC50 value of 6.38 mg/mL. The SDS-PAGE results showed that alcalase hydrolysate represented a unique pattern compared to others, which yielded potent ACE inhibitory peptides with molecular weight distribution lower than 20 kDa. The evaluation of the relationship between DH and IC50 values of alcalase and flavourzyme hydrolysates revealed that the trend between those parameters was related to the type of the protease used. We concluded that the tested SHHs would be used as a potential source of functional ACE inhibitory peptides for physiological benefits.

  17. Synthesis and biological studies of highly concentrated lisinopril-capped gold nanoparticles for CT tracking of angiotensin converting enzyme (ACE)

    Ghann, William E.; Aras, Omer; Fleiter, Thorsten; Daniel, Marie-Christine

    2011-05-01

    For patients with a history of heart attack or stroke, the prevention of another cardiovascular or cerebrovascular event is crucial. The development of cardiac and pulmonary fibrosis has been associated with overexpression of tissue angiotensin-converting enzyme (ACE). Recently, gold nanoparticles (GNPs) have shown great potential as X-ray computed tomography (CT) contrast agents. Since lisinopril is an ACE inhibitor, it has been used as coating on GNPs for targeted imaging of tissue ACE in prevention of fibrosis. Herein, lisinopril-capped gold nanoparticles (LIS-GNPs) were synthesized up to a concentration of 55 mgAu/mL. Their contrast was measured using CT and the results were compared to Omnipaque, a commonly used iodine-based contrast agent. The targeting ability of these LIS-GNPs was also assessed.

  18. Renal uptake of dimercaptosuccinic acid and glomerular filtration rate in chronic nephropathy at angiotensin converting enzyme inhibition

    Kamper, A L; Thomsen, H S; Nielsen, S L; Strandgaard, S

    1990-01-01

    function. Scintigrams of the kidneys showed an unaltered distribution of DMSA during treatment. GFR estimated by 51Cr-EDTA plasma clearance fell by 14% (P less than 0.01), but renal uptake of 99mTc-DMSA increased by 10% (P less than 0.01). It is concluded that DMSA in chronic renal failure is mainly taken......Glomerular filtration rate (GFR) and renal uptake of dimercaptosuccinic acid (DMSA) were measured in 31 patients with progressive chronic nephropathy before and immediately after the start of treatment with angiotensin converting enzyme (ACE) inhibitor in order to control adverse effects on kidney...... up by the tubular cells from the peritubular capillaries since the uptake was unaffected by the acute decrease in GFR....

  19. Inhibition of tissue angiotensin converting enzyme by perindopril: in vivo assessment in the rat using radioinhibitor binding displacement

    Jackson, B.; Cubela, R.B.; Johnston, C.I.

    1988-06-01

    Changes in angiotensin converting enzyme (ACE) derived from plasma, lung, aorta, brain, kidney and testis were measured in rats treated with perindopril. Angiotensin converting enzyme was measured by a radio inhibitor binding method using 125I351A. Rats were gavage fed perindopril (1, 4 and 8 mg/kg) and changes followed over 48 hr. Plasma and kidney ACE were both affected acutely with reduction of 125I351A binding to less than 5% of that in control animals 1 and 2 hr after gavage. Ligand binding to ACE in plasma and kidney returned to control levels after 24 hr. Ligand binding to ACE in lung, aorta and brain also was displaced after perindopril treatment. Changes were of a lesser degree than in plasma or kidney. Maximal effect was 1 to 4 hr after treatment and persisted through 24 hr postgavage. Ligand binding to ACE from testis was little altered over the time period of study. In a dose varying study rats were gavage fed perindopril (0-32 mg/kg) and tissues were studied 4 hr later. Ligand binding to plasma and kidney ACE was displaced by 50% at a dose of 1 mg/kg or less, whereas a dose of 16 to 32 mg/kg was required for a similar effect on ACE in lung, aorta and brain. ACE in testis was only affected to a small degree at a dose of 32 mg/kg. ACE is tissues was inhibited differentially after oral treatment with perindopril. Although differing in bioavailability, bioactivation of the drug or different binding properties of the enzyme could all account for the results, the most likely explanation is that there is variation in tissue penetration of the drug.

  20. Multifunctional gold nanoparticles for targeted imaging of angiotensin converting enzyme design, characterization, and application

    Ghann, William Emmanuel

    Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in the United States with approximately one in every three death being attributed to these diseases. The overarching problem with heart diseases is that once a person has suffered from an attack, there is a high likelihood of a recurrent attack. According to the American Heart Association, approximately 785,000 Americans per year suffer from heart attacks for the first time and about half of the aforementioned experience an ensuing attack. The second attack is often fatal, and therefore relapse prevention is crucial. One of the possible ways of averting the recurrence of such an attack is through the precise monitoring of the preceding biomarkers or risk indicators. This project encompasses the design, synthesis, characterization, and application of nanoparticle-based contrast agents that can potentially be used in the monitoring of the reemergence of a biomarker expressed after a person has suffered myocardial infarction. The overexpression of this biomarker, angiotensin converting enzyme (ACE), is also associated with development of cardiac and pulmonary fibrosis. To this end, highly concentrated gold nanoparticles have been synthesized and conjugated to Lisinopril, an ACE inhibitor, for the molecular imaging of ACE using X-ray CT. Various stabilities studies were conducted to verify the resistance of this gold nanoprobe in biological relevant media. They have also been successfully used in X-ray computed tomography to visualize tissue ACE and thus render them potentially versatile in the monitoring of cardiovascular diseases. An MRI tag was also conjugated to the gold nanoparticle affording the opportunity for bimodal imaging of ACE. This contrast agent could further be used for the quantification using K-edge CT of the relationship between the amount of the said marker and its role in predicting the possibility of a successive heart attack. The prepared nanoparticle-based contrast

  1. The influence of angiotensin-converting enzyme inhibition on renal tubular function in progressive chronic nephropathy

    Kamper, A L; Holstein-Rathlou, N H; Leyssac, P P; Strandgaard, S

    1996-01-01

    The influence of angiotensin-converting enzyme (ACE) inhibition on renal tubular function in progressive chronic nephropathy was investigated in 69 patients by the lithium clearance (C(Li)) method. Studies were done repeatedly for up to 2 years during a controlled trial on the effect of enalapril...... on progression of renal failure. The pattern of proteinuria was followed over the first 9 months. At baseline, the glomerular filtration rate (GFR) was 5 to 68 mL/min. Absolute proximal tubular reabsorption rate of fluid (APR), estimated as the difference between GFR and C(Li), was 1 to 54 m......L/min. Calculated fractional proximal reabsorption (FPR) was moderately subnormal. During the study, GFR decreased and sodium clearance was unchanged; fractional excretion of sodium therefore increased. In the group of patients randomized to treatment with enalapril (n = 34), GFR at 1 month was 83% (P < 0.001) and...

  2. Inhibition of central angiotensin-converting enzyme with enalapril protects the brain from ischemia/reperfusion injury in normotensive rat

    H Panahpour

    2010-03-01

    Full Text Available "n  Background and the Purpose of the study: Central Angiotensin Converting Enzyme (ACE has an important role on cerebral microcirculation and metabolism. However, its role in terms of protecting the brain from ischemic/reperfusion (I/R injury are debatable. This study evaluated the role of ACE, using enalapril as ACE inhibitor, in protection of the brain from I/R injury during transient focal cerebral ischemia (TFCI in normotensive rat. Method: Male Sprague Dawley rats (280-320g randomly assigned to control ischemic and enalapril pre-treated ischemic groups. Enalapril was injected intraperitoneally 1 h before middle cerebral artery occlusion (MCAO at the dose of 0.03 or 0.1 mg/kg. Cerebral ischemia was induced by 60 min MCAO followed by 24 hrs reperfusion. After evaluation of neurological deficit scores (NDS the animal was sacrificed for assessment of cerebral infarction and edema. Results: TFCI induced cerebral infarctions (283±18 mm3, brain edema (4.1±0.4% and swelling (9.8±1.5% with NDS of 3.11±0.36. Non-hypotensive dose of enalapril (0.03 mg/kg improved NDS (1.37±0.26, reduced cerebral infarction (45%, brain edema (54% and swelling of the lesioned hemispheres (34% significantly. However, hypotensive dose of enalapril (0.1 mg/kg could improve neurological activity (1.67±0.31 and failed to reduce cerebral infarction (276±39mm3 and swelling (10.4±1.4%. Conclusion: In the rat model of transient focal cerebral ischemia, inhibition of angiotensin converting enzyme with non-hypotensive doses of enalapril has the benefit of improving neurological activity, reducing cerebral infarction, brain swelling and edema of acute ischemic stroke. Therefore, it is reasonable to conclude that central renin-angiotensin system may participate in ischemic/reperfusion injury of the cerebral cortex.

  3. Loss of collectrin, an angiotensin-converting enzyme 2 homolog, uncouples endothelial nitric oxide synthase and causes hypertension and vascular dysfunction

    Cechova, Sylvia; Zeng, Qing; Billaud, Marie;

    2013-01-01

    Collectrin is an orphan member of the renin-angiotensin system and is a homolog of angiotensin-converting enzyme 2, sharing ≈50% sequence identity. Unlike angiotensin-converting enzyme 2, collectrin lacks any catalytic domain. Collectrin has been shown to function as a chaperone of amino acid...

  4. Natural products inhibitors of the angiotensin converting enzyme (ACE: a review between 1980 - 2000 Produtos naturais inibidores da enzima conversora de angiotensina (ECA: uma revisão entre 1980 - 2000

    José M. Barbosa-Filho

    2006-09-01

    Full Text Available Inhibition of Angiotensin Converting Enzyme (ACE is a modern therapeutic target in the treatment of hypertension. Within the enzyme cascade of the renin-angiotensin system, ACE removes histidyl-leucine from angiotensin I to form the physiologically active octapeptide angiotensin II, one of the most potent known vasoconstrictors. Therefore, a rationale for treating hypertension would be to administer drugs or natural compounds which selectively inhibit ACE. The present work constitutes a review of the literature of plants and chemically defined molecules from natural sources with in vitro anti-hypertensive potential based on the inhibition of ACE. The review refers to 321 plants, the parts utilized, type of extract and whether they are active or not. It includes also the names of 158 compounds isolated from higher plants, marine sponges and algae, fungi and snake venom. Some aspects of recent research with natural products directed to produce anti-hypertensive drugs are discussed. In this review, 148 references were cited.A inibição da Enzima Conversora da Angiotensina (ECA é um alvo terapêutico moderno e eficaz no tratamento da hipertensão arterial. Na cascata enzimática que envolve o sistema renina-angiotensina, a ECA promove a remoção dos aminoácidos histidil-leucina da angiotensina I para formar o octapeptídio angiotensina II, a qual é fisiologicamente ativa em diversos sistemas, e considerado como um dos mais potentes vasoconstrictores endógenos conhecido. Portanto, uma racionalidade no tratamento da hipertensão seria administrar drogas ou compostos de origem natural que inibam seletivamente a ECA. O presente estudo constitui uma revisão da literatura sobre plantas e moléculas de origem natural com potencial anti-hipertensivo, baseado na inibição in vitro da ECA. A revisão referencia 321 plantas, partes usadas, tipo de extrato e se é ativo ou não. Inclui ainda o nome de 158 compostos isolados de plantas superiores

  5. Lactic acid bacteria: inhibition of angiotensin converting enzyme in vitro and in vivo

    Fuglsang, Anders; Rattray, Fergal; Nilsson, Dan;

    2003-01-01

    A total of 26 strains of wild-type lactic acid bacteria, mainly belonging to Lactococcus lactis and Lactobacillus helveticus , were assayed in vitro for their ability to produce a milk fermentate with inhibitory activity towards angiotensin converting enzyme (ACE). It was clear that the test...

  6. Angiotensin converting enzyme and vascular endothelial growth factor responses to exercise training in claudicants: the role of ace inhibition

    Ng, P

    2009-01-01

    Exercise training is well recognised as an effective treatment for intermittent claudication. The mechanism underlying exercise induced improvements is multi-factorial but remains poorly understood. Low angiotensin-converting enzyme (ACE) activity has been associated with enhanced responses to endurance training. Specifically, low ACE activity has been associated with improved muscle metabolism, endothelial function, and suppressed inflammatory responses; processes linked with exercise traini...

  7. 96孔板法用于高通量血管紧张素转化酶抑制剂体外检测%Establishment of in Vitro High-throughput Activity Detection Method for Angiotensin Converting Enzyme Inhibitors Based on 96 Well Plates

    骆琳; 丁青芝; 马海乐

    2012-01-01

    A high throughput method for the determination of angiotensin converting enzyme (ACE) inhibitory activity, using 96-well plate technology, has been developed. Hydrolysis of N-[3-(2-furyl) acryloyl[L-phenylalanyl-glycyl-glycine (FAPGG) to N-[3-(2-furyl)acryloyl]-L-phenylalanine (FAP) and glycyl-glycine(GG) by ACE was quantified by measuring the decrease in absorbance at 340 nm to evaluate the activity of ACE. The percentage inhibition of angiotensin converting enzyme inhibitory (ACEI) was determined by comparing the results of control and test samples. The effects of different buffer systems, chloride ion concentration, ACE activity (ACE enzyme concentration), pH value of buffer system on the test of the activity of angiotensin converting enzyme inhibitors in vitro model reaction system of detection were investigated. The new method can detect ACE inhibitory activity of no more than 96 ACEI samples in 10 s or so on microplate-reader for ELISA. For different batches of sample, the RSD was less than 0. 001%, p = 0. 667(>0. 05), which shows no significant difference between the results measured. The method is simple, accurate, stable, and reliable in antihyperten-sive peptide in vitro inhibitory activity of ACE measured. The method was used to detect a famous angiotensin converting enzyme inhibitors product named Captopril and a IC50 value ( Half inhibitory concentration) of 16.19 nmol/L was obtained, which is consistent with the results have been reported in extensive literature.%为在体外迅速检测血管紧张素转化酶抑制剂( ACEI)的抑制活性,选用96孔板,以呋喃丙烯酰三肽(FAPGG)为模拟底物,通过检测血管紧张素转化酶(ACE)酶解FAPGG生成N-[3-(呋喃)丙稀醇酰-2-苯丙氨酸( FAP)和双甘氨肽(GG)后340 nm处吸光值的下降衡量ACE的活性,采用加入ACEI前后ACE的活性变化衡量ACEI的活性.考察了不同缓冲体系、Cl-浓度、ACE酶活性(ACE酶浓度)、缓冲体系的pH值等对上述检测模型反应

  8. Angiotensin-converting enzyme gene (ACE) insertion/deletion polymorphism in Mexican populations.

    Vargas-Alarcón, Gilberto; Hernández-Pacheco, Guadalupe; Rodríguez-Pérez, José Manuel; Pérez-Hernández, Nonanzit; Pavón, Zinnia; Fragoso, José Manuel; Juarez-Cedillo, Teresa; Villarreal-Garza, Cynthia; Granados, Julio

    2003-12-01

    The angiotensin-converting enzyme gene (ACE) insertion/deletion polymorphism was determined in 211 Mexican healthy individuals belonging to different Mexican ethnic groups (98 Mestizos, 64 Teenek, and 49 Nahuas). ACE polymorphism differed among Mexicans with a high frequency of the D allele and the D/D genotype in Mexican Mestizos. The D/D genotype was absent in Teenek and present in only one Nahua individual (2.0%). When comparisons were made, we observed that Caucasian, African, and Asian populations presented the highest frequencies of the D allele, whereas Amerindian (Teenek and Pima) and Australian Aboriginals showed the highest frequencies of the I allele. The distribution of I/D genotype was heterogeneous in all populations: Australian Aboriginals presented the lowest frequency (4.9%), whereas Nahuas presented the highest (73.4%). The present study shows the frequencies of a polymorphism not analyzed previously in Mexican populations and establishes that this polymorphism distinguishes the Amerindian populations of other groups. On the other hand, since ACE alleles have been associated with genetic susceptibility to developing cardiovascular diseases and hypertension, knowledge of the distribution of these alleles could help to define the true significance of ACE polymorphism as a genetic susceptibility marker in the Amerindian populations. PMID:15018037

  9. IMPACT OF ANGIOTENSIN-CONVERTING ENZYME GENE POLYMORPHISM ON THE DEVELOPMENT OF INSULIN RESISTANCE SYNDROME

    G. E. Roitberg

    2013-01-01

    Full Text Available Objective: to analyze the distribution of components of insulin resistance (IR syndrome and to study the frequency of their combinations in relation to the genotypes and allelic variants of the angiotensin-converting enzyme (ACE gene.Subjects and methods. A group of clinically healthy patients (50 women and 42 men with different genotypes of the ACE gene was examined.The distribution of IR syndrome components and the frequency of their combinations were analyzed in relation to the genotypes and allelicvariants of the ACE gene.Results. A group of D allele carriers compared to A allele ones showed a pronounced tendency for the frequency of IR to reduce due to thehigher proportion of patients with complete IR syndrome. This observation becomes statistically significant in the assessment of homozygous variants of the ACE gene. At the same time dyslipidemia and hypertension in the presence of IR significantly more frequently occurred in patients with the DD genotype than in those with genotype II.Conclusion. There was a marked predominance of the manifestations of IR syndrome with a complete set of components in the DD genotypicgroup, which confirms the significant strong association between ACE gene polymorphism and IR syndrome.

  10. Skeletal muscle strength in older adults. Angiotensin-converting enzyme (ACE genotype affects: an UPDATE

    ANA PEREIRA

    2011-06-01

    Full Text Available Problem Statement : Previous studies have associated angiotensin-converting enzyme (ACE with variability inthe skeletal muscle baseline strength, though conclusions have been inconsistent across investigations.Approach: The purpose of this study was to review the most important studies that have been exanimate thepossible association between ACE genotype and skeletal muscle baseline strength in elite male and femaleathletes involved in elderly populations. This research is needed because the possibility that the DD genotypemay be associated with a greater proportion of fast twitch fibers could explain the influence of the ACE D alleleupon strength/ power, particularly at high velocities, but this evidence remains equivocal in older people becausemore studies are necessary.Results: Thus, according to scientific evidence, changes in muscle strength with exercise training in olderindividuals may be dependent on ACE I/D genotype. Of note, the results provide a novel insight that thesegenetic variations may interact to determine muscle mass in older women specially. The determination of thispredisposition in this population, highlighting the interest of study, for the prophylactic attitude on the factorsand causes of aging (sarcopenia, osteoporosis, risk of falls, reduction of functional physical go through thisanalysis.Conclusions/Recommendations: In this work, the state of the art related to the influence of the ACE genotypeon skeletal muscle strength was presented and some important relations were reported

  11. Serum Levels of Copper, Ceruloplasmin and Angiotensin Converting Enzyme among Silicotic and Non-Silicotic Workers

    Beshir, Safia; Aziz, Hisham; Shaheen, Weam; Eltahlawy, Eman

    2015-01-01

    BACKGROUND: Silicosis is the most frequently occurring pneumoconiosis. AIM: Measurement of serum levels of Angiotensin converting enzyme (ACE), Copper (Cu) and Ceruloplasmin (Cp) in cement workers occupationally exposed to silica dust as biomarkers of exposure rather than biomarkers of effect for silicosis. METHODS: Plain chest X-ray & pulmonary functions were done for 30 silicotic and 42 non-silicotic workers and 42 controls. CT scan was done for the exposed groups. Serum levels of Cu, Cp and ACE were estimated. RESULTS: The results showed a higher significant difference between the exposed groups and controls, and between the two exposed groups regarding the mean levels of all measured biochemical parameters. The pulmonary functions were significantly lower among silicotic workers than controls and non-silicotic groups. There was a significant positive correlation between duration of employment and serum ACE and Cu. CONCLUSION: Since respirable dust exposure-linked lung fibrosis disease is non-curable, the biochemical parameters (Cu, ACE and Cp) can be used as exposure biomarkers to silica dust, providing a better way for early diagnosis of this deadly disease. Down regulating the inflammatory responses could potentially reduce the adverse clinical pulmonary effects of air pollution.

  12. Pengaruh Pemberian Ekstrak Etanol Buah Mengkudu terhadap Aktivitas Angiotensin Converting Enzyme (ACE) pada Tikus Wistar yang Mendapat Diet Natrium

    Syahreza, Adri

    2012-01-01

    Hypertension is now a global problem because of the prevalence continues to increase in line with lifestyle changes. One of hypertension cause is excess intake of sodium thus will increase the fluid volume in the body. One of regulates the fluid balance in the body is mechanism of renin angiotensin aldosterone system (RAAS). Increasing activity of angiotensin converting enzyme (ACE) in the body will lead to hypertension through RAAS. ACE activation can be inhibited by ACE In...

  13. Angiotensin-converting enzyme insertion/deletion polymorphism does not influence the restenosis rate after coronary stent implantation

    Ferrari, Markus; Mudra, Harald; Grip, Lars; Voudris, Vassilis; Schächinger, Volker; de Jaegere, Peter; Rieber, Johannes; Hausmann, Dirk; Rothman, Martin; Koschyk, Dietmar H.; Figulla, Hans R

    2002-01-01

    Background. Experimental studies have shown an activation of the angiotensin-converting enzyme (ACE) system as a response to endothelial injury. Recent publications have elucidated the hypothesis that the ACE gene polymorphism may influence the level of late luminal loss after coronary stent implantation. It is still unclear whether the polymorphism of the angiotensin gene is a major predictor of the extent of neointimal hyperplasia. In this multicenter study, we therefore tested the relation...

  14. Angiotensin converting enzyme inhibition does not affect the response to exogenous angiotensin II in the human forearm.

    Lyons, D.; D. Stewart; Webster, J; Benjamin, N

    1994-01-01

    Suppression of endogenous levels of angiotensin II by angiotensin converting enzyme inhibition, may result in up-regulation of vascular AT1 receptors. We have evaluated the effects of orally administered enalapril on angiotensin II induced vasoconstriction in the human forearm. Subjects received in random order, enalapril (20 mg) or matched placebo daily for 2 weeks. Forearm blood flow response to increasing doses of angiotensin II was measured using venous occlusion plethysmography at the be...

  15. The angiotensin-converting enzyme (ACE gene family of Anopheles gambiae

    Isaac R Elwyn

    2005-12-01

    Full Text Available Abstract Background Members of the M2 family of peptidases, related to mammalian angiotensin converting enzyme (ACE, play important roles in regulating a number of physiological processes. As more invertebrate genomes are sequenced, there is increasing evidence of a variety of M2 peptidase genes, even within a single species. The function of these ACE-like proteins is largely unknown. Sequencing of the A. gambiae genome has revealed a number of ACE-like genes but probable errors in the Ensembl annotation have left the number of ACE-like genes, and their structure, unclear. Results TBLASTN and sequence analysis of cDNAs revealed that the A. gambiae genome contains nine genes (AnoACE genes which code for proteins with similarity to mammalian ACE. Eight of these genes code for putative single domain enzymes similar to other insect ACEs described so far. AnoACE9, however, has several features in common with mammalian somatic ACE such as a two domain structure and a hydrophobic C terminus. Four of the AnoACE genes (2, 3, 7 and 9 were shown to be expressed at a variety of developmental stages. Expression of AnoACE3, AnoACE7 and AnoACE9 is induced by a blood meal, with AnoACE7 showing the largest (approximately 10-fold induction. Conclusion Genes coding for two-domain ACEs have arisen several times during the course of evolution suggesting a common selective advantage to having an ACE with two active-sites in tandem in a single protein. AnoACE7 belongs to a sub-group of insect ACEs which are likely to be membrane-bound and which have an unusual, conserved gene structure.

  16. The impact of telmisartan on angiotensin converting enzyme 2 mRNA expression in monocyte-derived macrophages of diabetic hypertensive patients

    李永勤

    2013-01-01

    Objective To investigate the effects of telmisartan on the expression of angiotensin converting enzyme 2(ACE2) mRNA in monocyte-derived macrophages of hypertensive patients accompanied with diabetes. Methods 62 essential hypertensive patients accompanied with

  17. Insertion/deletion polymorphism of the angiotensin-converting enzyme gene and the risk of hypertension among residents of two cities, South-South Nigeria

    Mary Esien Kooffreh

    2014-01-01

    Conclusion: The I/D polymorphism of the angiotensin-converting enzyme gene was a risk factor for hypertension in the sample population of Calabar and Uyo. This research will form baseline information for subsequent molecular studies in this population.

  18. A Tricholoma matsutake Peptide with Angiotensin Converting Enzyme Inhibitory and Antioxidative Activities and Antihypertensive Effects in Spontaneously Hypertensive Rats

    Geng, Xueran; Tian, Guoting; Zhang, Weiwei; Zhao, Yongchang; Zhao, Liyan; Wang, Hexiang; Ng, Tzi Bun

    2016-01-01

    Hypertension is a major risk factor for cardiovascular disease. A crude water extract of the fruiting bodies of a highly prized mushroom Tricholoma matsutakei exerted an antihypertensive action on spontaneously hypertensive rats (SHRs) at a dosage of 400 mg/kg. An angiotensin converting enzyme (ACE) inhibitory peptide with an IC50 of 0.40 μM was purified from the extract and designated as TMP. Its amino acid sequence was elucidated to be WALKGYK through LC-MS/MS analysis. The Lineweaver-Burk plot suggested that TMP was a non-competitive inhibitor of ACE. A short-term assay of antihypertensive activity demonstrated that TMP at the dosage of 25 mg/kg could significantly lower the systolic blood pressure (SBP) of SHRs. TMP exhibited remarkable stability over a wide range of temperatures and pH values. It also demonstrated 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. The aforementioned activities of TMP were corroborated by utilizing the synthetic peptide. Hence T. matsutake can be used as a functional food to help prevent hypertension- associated diseases. PMID:27052674

  19. Retroviruses Pseudotyped with the Severe Acute Respiratory Syndrome Coronavirus Spike Protein Efficiently Infect Cells Expressing Angiotensin-Converting Enzyme 2

    Moore, Michael J.; Dorfman, Tatyana; Li, Wenhui; Wong, Swee Kee; Li, Yanhan; Kuhn, Jens H.; Coderre, James; Vasilieva, Natalya; Han, Zhongchao; Greenough, Thomas C.; Farzan, Michael; Choe, Hyeryun

    2004-01-01

    Infection of receptor-bearing cells by coronaviruses is mediated by their spike (S) proteins. The coronavirus (SARS-CoV) that causes severe acute respiratory syndrome (SARS) infects cells expressing the receptor angiotensin-converting enzyme 2 (ACE2). Here we show that codon optimization of the SARS-CoV S-protein gene substantially enhanced S-protein expression. We also found that two retroviruses, simian immunodeficiency virus (SIV) and murine leukemia virus, both expressing green fluorescent protein and pseudotyped with SARS-CoV S protein or S-protein variants, efficiently infected HEK293T cells stably expressing ACE2. Infection mediated by an S-protein variant whose cytoplasmic domain had been truncated and altered to include a fragment of the cytoplasmic tail of the human immunodeficiency virus type 1 envelope glycoprotein was, in both cases, substantially more efficient than that mediated by wild-type S protein. Using S-protein-pseudotyped SIV, we found that the enzymatic activity of ACE2 made no contribution to S-protein-mediated infection. Finally, we show that a soluble and catalytically inactive form of ACE2 potently blocked infection by S-protein-pseudotyped retrovirus and by SARS-CoV. These results permit studies of SARS-CoV entry inhibitors without the use of live virus and suggest a candidate therapy for SARS. PMID:15367630

  20. New perspectives in the renin-angiotensin-aldosterone system (RAAS I: endogenous angiotensin converting enzyme (ACE inhibition.

    Miklós Fagyas

    Full Text Available Angiotensin-converting enzyme (ACE inhibitors represent the fifth most often prescribed drugs. ACE inhibitors decrease 5-year mortality by approximately one-fifth in cardiovascular patients. Surprisingly, there are reports dating back to 1979 suggesting the existence of endogenous ACE inhibitors, which endogenous inhibitory effects are much less characterized than that for the clinically administered ACE inhibitors. Here we aimed to investigate this endogenous ACE inhibition in human sera. It was hypothesized that ACE activity is masked by an endogenous inhibitor, which dissociates from the ACE when its concentration decreases upon dilution. ACE activity was measured by FAPGG hydrolysis first. The specific (dilution corrected enzyme activities significantly increased by dilution of human serum samples (23.2 ± 0.7 U/L at 4-fold dilution, 51.4 ± 0.3 U/L at 32-fold dilution, n = 3, p = 0.001, suggesting the presence of an endogenous inhibitor. In accordance, specific enzyme activities did not changed by dilution when purified renal ACE was used, where no endogenous inhibitor was present (655 ± 145 U/L, 605 ± 42 U/L, n = 3, p = 0.715, respectively. FAPGG conversion strongly correlated with angiotensin I conversion suggesting that this feature is not related to the artificial substrate. Serum samples were ultra-filtered to separate ACE (MW: 180 kDa and the hypothesized inhibitor. Filtering through 50 kDa filters was without effect, while filtering through 100 kDa filters eliminated the inhibiting factor (ACE activity after <100 kDa filtering: 56.4 ± 2.4 U/L, n = 4, control: 26.4 ± 0.7 U/L, n = 4, p<0.001. Lineweaver-Burk plot indicated non-competitive inhibition of ACE by this endogenous factor. The endogenous inhibitor had higher potency on the C-terminal active site than N-terminal active site of ACE. Finally, this endogenous ACE inhibition was also present in mouse, donkey, goat, bovine sera besides men (increasing of specific ACE activity

  1. Angiotensin-converting enzyme genotype and late respiratory complications of mustard gas exposure

    Humphries Steve E

    2008-08-01

    Full Text Available Abstract Background Exposure to mustard gas frequently results in long-term respiratory complications. However the factors which drive the development and progression of these complications remain unclear. The Renin Angiotensin System (RAS has been implicated in lung inflammatory and fibrotic responses. Genetic variation within the gene coding for the Angiotensin Converting Enzyme (ACE, specifically the Insertion/Deletion polymorphism (I/D, is associated with variable levels of ACE and with the severity of several acute and chronic respiratory diseases. We hypothesized that the ACE genotype might influence the severity of late respiratory complications of mustard gas exposure. Methods 208 Kurdish patients who had suffered high exposure to mustard gas, as defined by cutaneous lesions at initial assessment, in Sardasht, Iran on June 29 1987, underwent clinical examination, spirometric evaluation and ACE Insertion/Deletion genotyping in September 2005. Results ACE genotype was determined in 207 subjects. As a continuous variable, FEV1 % predicted tended to be higher in association with the D allele 68.03 ± 20.5%, 69.4 ± 21.4% and 74.8 ± 20.1% for II, ID and DD genotypes respectively. Median FEV1 % predicted was 73 and this was taken as a cut off between groups defined as having better or worse lung function. The ACE DD genotype was overrepresented in the better spirometry group (Chi2 4.9 p = 0.03. Increasing age at the time of exposure was associated with reduced FEV1 %predicted (p = 0.001, whereas gender was not (p = 0.43. Conclusion The ACE D allele is associated with higher FEV1 % predicted when assessed 18 years after high exposure to mustard gas.

  2. Carotid remodeling of hypertensive subjects and polymorphism of the angiotensin-converting enzyme gene

    李世军; 孙宁玲; 周素敏

    2004-01-01

    Background This study was designed to investigate the relationships between changes in the structure and function of carotid arteries and angiotensin converting enzyme (ACE) gene polymorphism in Chinese hypertensive subjects. Methods Multiplex polymerase chain reaction amplification was used to evaluate the ACE gene insertion/deletion (I/D) polymorphism. High-resolution B-mode ultrasound examinations were performed to detect parameters of carotid artery remodeling. Results Intima-media thickness (IMT) was significantly different among the DD, ID and II genotypes of ACE (DD>ID>II, P0.05) in hypertensive subjects. The frequency of the DD gene and D allele of ACE were higher in patients with thickening carotid than in patients with normal carotid (70.4% vs 24.1%, and 79.5% vs 40.5%, respectively, P<0.001). In multiple stepwise regression analysis, independent risk factors for increased carotid IMT in hypertensive subjects were ACE genotypes (P<0.001), age (P<0.001) and carotid internal diameter (P=0.032). Moreover, triglycerides and total cholesterol were higher in patients with the DD genotype than in those with the II genotype (P<0.05). Conclusions The I/D polymorphism of the ACE gene was related to IMT, but not to internal diameter, distensibility and stiffness of the carotid in Chinese hypertensive subjects. ACE gene polymorphism was a main risk factor for increased carotid IMT. These results may imply that there is a link between lipid metabolism and ACE genotype polymorphism in Chinese hypertensive subjects.

  3. Inhibitory effects of kiwifruit extract on human platelet aggregation and plasma angiotensin-converting enzyme activity.

    Dizdarevic, Lili L; Biswas, Dipankar; Uddin, M D Main; Jørgenesen, Aud; Falch, Eva; Bastani, Nasser E; Duttaroy, Asim K

    2014-01-01

    Previous human studies suggest that supplementation with kiwifruits lowers several cardiovascular risk factors such as platelet hyperactivity, blood pressure and plasma lipids. The cardiovascular health benefit of fruit and vegetables is usually attributed to the complex mixture of phytochemicals therein; however, kiwifruit's cardioprotective factors are not well studied. In this study, we investigated the effects of kiwifruit extract on human blood platelet aggregation and plasma angiotensin-converting enzyme (ACE) activity. A sugar-free, heat-stable aqueous extract with molecular mass less than 1000 Da was prepared from kiwifruits. Typically, 100 g kiwifruits produced 66.3 ± 5.8 mg (1.2 ± 0.1 mg CE) of sugar-free kiwifruit extract (KFE). KFE inhibited both human platelet aggregation and plasma ACE activity in a dose-dependent manner. KFE inhibited platelet aggregation in response to ADP, collagen and arachidonic acid, and inhibitory action was mediated in part by reducing TxA2 synthesis. The IC50 for ADP-induced platelet aggregation was 1.6 ± 0.2 mg/ml (29.0 ± 3.0 μg CE/ml), whereas IC50 for serum ACE was 0.6 ± 0.1 mg/ml (11.0 ± 1.2 μg CE/ml). Consuming 500 mg of KFE (9.0 mg CE) in 10 g margarine inhibited ex vivo platelet aggregation by 12.7%, 2 h after consumption by healthy volunteers (n = 9). All these data indicate that kiwifruit contains very potent antiplatelet and anti-ACE components. Consuming kiwifruits might be beneficial as both preventive and therapeutic regime in cardiovascular disease. PMID:24219176

  4. Angiotensin-converting enzyme inhibitory and antioxidant activities of enzymatically synthesized phenolic and vitamin glycosides.

    Charles, Rajachristu Einstein; Ponrasu, Thangavel; Sivakumar, Ramaiah; Divakar, Soundar

    2009-03-01

    Amyloglucosidase from Rhizopus mould and beta-glucosidase from sweet almond were employed for the preparation of phenolic and vitamin glycosides of vanillin, N-vanillylnonanamide, DL-dopa, dopamine, curcumin, alpha-tocopherol (vitamin E), pyridoxine (vitamin B(6)), ergocalciferol (vitamin D(2)), thiamin (vitamin B(1)) and riboflavin (vitamin B(2)). Approx. 20 enzymatically prepared phenolic and vitamin glycosides were subjected to ACE (angiotensin-converting enzyme) inhibition activity measurements, and 14 glycosides were tested for antioxidant activities. Both phenolic and vitamin glycosides exhibited IC(50) values for ACE inhibition in the 0.52+/-0.03-3.33+/-0.17 mM range and antioxidant activities ranging from 0.8+/-0.04 to 1.18+/-0.06 mM. Comparable ACE inhibition values were observed between free phenols and vitamin glycosides. However, antioxidant activities of glycosides were, in general, lesser than those of free phenols. Best IC(50) value for ACE inhibition were observed for 11-O-(D-fructofuranosyl)thiamin (0.52+/-0.03 mM), 3-hydroxy-4-O-(6-D-sorbitol)phenylalanine (0.56+/-0.03 mM), 4-O-(beta-D-glucopyranosyl)vanillin (0.61+/-0.03 mM), 4-O-(D-galactopyranosyl)vanillin (0.61+/-0.03 mM) and pyridoxine-D-glucoside (0.84+/-0.04 mM). Similarly, best IC(50) values for antioxidant activity were observed for 1,7-O-(bis-beta-D-glucopyranosyl)curcumin (0.8+/-0.04 mM), 4-O-(beta-D-glucopyranosyl)vanillin (0.9+/-0.05 mM), 3-hydroxy-4-O-(beta-D-galactopyranosyl-(1'-->4)beta-D-glucopyranosyl)phenylalanine (0.9+/-0.05 mM), 20-O-(D-glucopyranosyl)ergocalciferol (0.9+/-0.05 mM) and dopamine-D-galactoside (0.93+/-0.05 mM). PMID:18547170

  5. Association of polymorphisms in angiotensin-converting enzyme gene with gestational diabetes mellitus in Indian women

    Aggarwal, Parul; Agarwal, Nutan; Das, Nibhriti; Dalal, Krishna

    2016-01-01

    Background: Numerous genes have been reported in relation with gestational diabetes mellitus (GDM), but the findings were not consistently replicated across populations, or there have been no detailed studies on them. Previous literatures suggested that, out of all angiotensin converting enzyme (ACE) gene polymorphisms, only ACE insertion/deletion (I/D) gene polymorphism has a strong association with GDM in Asian Indian women. Aim: This study was devoted to evaluate the association of four single nucleotide polymorphisms (SNPs) ACE A240T, C1237T, G2350A and I/D with GDM and Type 2 diabetes mellitus. Materials and Methods: This study recruited 105 GDM cases, 119 Type 2 diabetes mellitus subjects and 120 controls. PCR-RFLP was used for identifying genotypes of ACE A240T, C1237T and G2350A and PCR was performed in the case of ACE I/D. Results: Significant associations of ACE SNP's, C1237T, and G2350A with GDM were observed. Haplotype analysis revealed the remarkably significant evidence of association with SNP combination ACE A240T, C1237T, G2350A, and I/D with GDM patients (P = 0.024). Individuals possessing haplotype “TTAI” (frequency 30% in GDM and 0 in controls) derived from these SNPs had 185 fold increased risk of developing GDM (95% of confidence interval: 11.13–3102.15), which was highest when compared with other 15 haplotypes. Conclusion: Shorter-range haplotypes were also significant, but the only consistently associated alleles were found to be in ACE C1237T, G2350A, and I/D. These results suggested that the variant in close proximity to ACE C1237T, G2350A and/or I/D modulates susceptibility to GDM and noninsulin dependent diabetes mellitus in Indian women. PMID:26958520

  6. Genetic Associations of Angiotensin-Converting Enzyme with Primary Intracerebral Hemorrhage: A Meta-analysis.

    Yuhao Sun

    Full Text Available A number of studies have reported an association of angiotensin-converting enzyme (ACE gene polymorphism with primary intracerebral hemorrhage (PICH, however the reports have demonstrated inconclusive results. To clarify this conflict, we updated the previously performed meta-analysis by Peck et al., which revealed negative results, by investigating the ACE polymorphism and its correlation to PICH.PubMed and Embase databases (through Dec 2012 were searched for English articles on the relationship of the I/D polymorphism in ACE with PICH in humans. Summary odds ratios (ORs were estimated and potential sources of heterogeneity and bias were explored.A total of 805 PICH cases and 1641 control cases obtained from 8 case-control studies were included. The results suggest that in dominant genetic models, the ACE I/D polymorphic variant was associated with a 58% increase in susceptibility risk of PICH (OR = 1.58; 95% CI = 1.07-2.35 for DD vs. DI+II. However, in the subgroup analysis based on race, a significant increased risk was found in Asian DD homozygote carriers (OR = 1.76 and 95% CI = 1.16-2.66 for DD vs. DI+II, but not in Caucasian DD homozygote carriers (OR = 1.18, 95% CI = 0.36-3.88, P = 0.784 for DD vs. DI+II. The heterogeneity between studies was remarkable, and its major sources of heterogeneity were due to the year in which the study was published. No potential publication bias was observed in dominant genetic models.These data demonstrated evidence of a positive association between ACE I/D polymorphism with PICH, and suggested that the ACE gene is a PICH susceptible gene in Asian populations.

  7. ANGIOTENSIN-CONVERTING ENZYME GENOTYPE AFFECTS SKELETAL MUSCLE STRENGTH IN ELITE ATHLETES

    Aldo Matos Costa

    2009-09-01

    Full Text Available Previous studies have associated angiotensin-converting enzyme (ACE D allele with variability in the skeletal muscle baseline strength, though conclusions have been inconsistent across investigations. The purpose of this study was to examine the possible association between ACE genotype and skeletal muscle baseline strength in elite male and female athletes involved in different event expertise. A group of 58 elite athletes, designated as Olympic candidates, were studied: 35 swimmers (19 males and 16 females, 18.8 ± 3.2 years and 23 triathletes (15 males and 8 females, 18.7 ± 3.0 years. The athletes were classified as: short (< 200m and middle (400m to 1500m distance athletes, respectively. For each subject the grip strength in both hands was measure using an adjustable mechanical hand dynamometer. The maximum height in both squat jump (SJ and counter movement jump (CMJ were also assessed, using a trigonometric carpet (Ergojump Digitime 1000; Digitest, Jyvaskyla, Finland. DNA extraction was obtained with Chelex 100® and genotype determination by PCR-RFLP methods. Both males and females showed significantly higher right grip strength in D allele carriers compared to II homozygote's. We found that allelic frequency differs significantly by event distance specialization in both genders (p < 0.05. In fact, sprinter D allele carriers showed the superior scores in nearly all strength measurements (p < 0.05, in both genders. Among endurance athletes, the results also demonstrated that female D allele carriers exhibited the higher performance right grip and CMJ scores (p < 0.05. In conclusion, the ACE D allele seems associated with skeletal muscle baseline strength in elite athletes, being easily identified in females

  8. DNA methylation analysis of the angiotensin converting enzyme (ACE gene in major depression.

    Peter Zill

    Full Text Available BACKGROUND: The angiotensin converting enzyme (ACE has been repeatedly discussed as susceptibility factor for major depression (MD and the bi-directional relation between MD and cardiovascular disorders (CVD. In this context, functional polymorphisms of the ACE gene have been linked to depression, to antidepressant treatment response, to ACE serum concentrations, as well as to hypertension, myocardial infarction and CVD risk markers. The mostly investigated ACE Ins/Del polymorphism accounts for ~40%-50% of the ACE serum concentration variance, the remaining half is probably determined by other genetic, environmental or epigenetic factors, but these are poorly understood. MATERIALS AND METHODS: The main aim of the present study was the analysis of the DNA methylation pattern in the regulatory region of the ACE gene in peripheral leukocytes of 81 MD patients and 81 healthy controls. RESULTS: We detected intensive DNA methylation within a recently described, functional important region of the ACE gene promoter including hypermethylation in depressed patients (p = 0.008 and a significant inverse correlation between the ACE serum concentration and ACE promoter methylation frequency in the total sample (p = 0.02. Furthermore, a significant inverse correlation between the concentrations of the inflammatory CVD risk markers ICAM-1, E-selectin and P-selectin and the degree of ACE promoter methylation in MD patients could be demonstrated (p = 0.01 - 0.04. CONCLUSION: The results of the present study suggest that aberrations in ACE promoter DNA methylation may be an underlying cause of MD and probably a common pathogenic factor for the bi-directional relationship between MD and cardiovascular disorders.

  9. Angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis activates Akt signaling to ameliorate hepatic steatosis.

    Cao, Xi; Yang, Fangyuan; Shi, Tingting; Yuan, Mingxia; Xin, Zhong; Xie, Rongrong; Li, Sen; Li, Hongbing; Yang, Jin-Kui

    2016-01-01

    The classical axis of renin-angiotensin system (RAS), angiotensin (Ang)-converting enzyme (ACE)/Ang II/AT1, contributes to the development of non-alcoholic fatty liver disease (NAFLD). However, the role of bypass axis of RAS (Angiotensin-converting enzyme 2 (ACE2)/Ang-(1-7)/Mas) in hepatic steatosis is still unclear. Here we showed that deletion of ACE2 aggravates liver steatosis, which is correlated with the increased expression of hepatic lipogenic genes and the decreased expression of fatty acid oxidation-related genes in the liver of ACE2 knockout (ACE2(-/y)) mice. Meanwhile, oxidative stress and inflammation were also aggravated in ACE2(-/y) mice. On the contrary, overexpression of ACE2 improved fatty liver in db/db mice, and the mRNA levels of fatty acid oxidation-related genes were up-regulated. In vitro, Ang-(1-7)/ACE2 ameliorated hepatic steatosis, oxidative stress and inflammation in free fatty acid (FFA)-induced HepG2 cells, and what's more, Akt inhibitors reduced ACE2-mediated lipid metabolism. Furthermore, ACE2-mediated Akt activation could be attenuated by blockade of ATP/P2 receptor/Calmodulin (CaM) pathway. These results indicated that Ang-(1-7)/ACE2/Mas axis may reduce liver lipid accumulation partly by regulating lipid-metabolizing genes through ATP/P2 receptor/CaM signaling pathway. Our findings support the potential role of ACE2/Ang-(1-7)/Mas axis in prevention and treatment of hepatic lipid metabolism. PMID:26883384

  10. Characterization of angiotensin-converting enzyme 2 ectodomain shedding from mouse proximal tubular cells.

    Fengxia Xiao

    Full Text Available Angiotensin-converting enzyme 2 (ACE2 is highly expressed in the kidney proximal tubule, where it cleaves angiotensin (Ang II to Ang-(1-7. Urinary ACE2 levels increase in diabetes, suggesting that ACE2 may be shed from tubular cells. The aim of this study was to determine if ACE2 is shed from proximal tubular cells, to characterize ACE2 fragments, and to study pathways for shedding. Studies involved primary cultures of mouse proximal tubular cells, with ACE2 activity measured using a synthetic substrate, and analysis of ACE2 fragments by immunoblots and mass spectrometry. The culture media from mouse proximal tubular cells demonstrated a time-dependent increase in ACE2 activity, suggesting constitutive ACE2 shedding. ACE2 was detected in media as two bands at ∼ 90 kDa and ∼ 70 kDa on immunoblots. By contrast, full-length ACE2 appeared at ∼ 100 kDa in cell lysates or mouse kidney cortex. Mass spectrometry of the two deglycosylated fragments identified peptides matching mouse ACE2 at positions 18-706 and 18-577, respectively. The C-terminus of the 18-706 peptide fragment contained a non-tryptic site, suggesting that Met(706 is a candidate ACE2 cleavage site. Incubation of cells in high D-glucose (25 mM (and to a lesser extent Ang II for 48-72 h increased ACE2 activity in the media (p<0.001, an effect blocked by inhibition of a disintegrin and metalloproteinase (ADAM17. High D-glucose increased ADAM17 activity in cell lysates (p<0.05. These data indicate that two glycosylated ACE2 fragments are constitutively shed from mouse proximal tubular cells. ACE2 shedding is stimulated by high D-glucose, at least partly via an ADAM17-mediated pathway. The results suggest that proximal tubular shedding of ACE2 may increase in diabetes, which could enhance degradation of Ang II in the tubular lumen, and increase levels of Ang-(1-7.

  11. Increased angiotensin-converting enzyme activity in the left ventricle after infarction

    V.C.W. Busatto

    1997-05-01

    Full Text Available An increase in angiotensin-converting enzyme (ACE activity has been observed in the heart after myocardial infarction (MI. Since most studies have been conducted in chronically infarcted individuals exhibiting variable degrees of heart failure, the present study was designed to determine ACE activity in an earlier phase of MI, before heart failure development. MI was produced in 3-month old male Wistar rats by ligation of the anterior branches of the left coronary artery, control rats underwent sham surgery and the animals were studied 7 or 15 days later. Hemodynamic data obtained for the anesthetized animals showed normal values of arterial blood pressure and of end-diastolic pressure in the right and left ventricular cavities of MI rats. Right and left ventricular (RV, LV muscle and scar tissue homogenates were prepared to determine ACE activity in vitro by measuring the velocity of His-Leu release from the synthetic substrate Hyp-His-Leu. ACE activity was corrected to the tissue wet weight and is reported as nmol His-Leu g-1 min-1. No significant change in ACE activity in the RV homogenates was demonstrable. A small nonsignificant increase of ACE activity (11 ± 9%; P0.05 was observed 7 days after MI in the surviving left ventricular muscle. Two weeks after surgery, however, ACE activity was 46 ± 11% (P<0.05 higher in infarcted rats compared to sham-operated rats. The highest ACE activity was demonstrable in the scar tissue homogenate. In rats studied two weeks after surgery, ACE activity in the LV muscle increased from 105 ± 7 nmol His-Leu g-1 min-1 in control hearts to 153 ± 11 nmol His-Leu g-1 min-1 (P<0.05 in the remaining LV muscle of MI rats and to 1051 ± 208 nmol His-Leu g-1 min-1 (P<0.001 in the fibrous scar. These data indicate that ACE activity increased in the heart after infarction before heart failure was demonstrable by hemodynamic measurements. Since the blood vessels of the scar drain to the remaining LV myocardium, the

  12. Association of circulating angiotensin converting enzyme activity with respiratory muscle function in infants

    Onufriou Anny

    2010-05-01

    Full Text Available Abstract Background Angiotensin converting enzyme (ACE gene contains a polymorphism, consisting of either the presence (I or absence (D of a 287 base pair fragment. Deletion (D is associated with increased circulating ACE (cACE activity. It has been suggested that the D-allele of ACE genotype is associated with power-oriented performance and that cACE activity is correlated with muscle strength. Respiratory muscle function may be similarly influenced. Respiratory muscle strength in infants can be assessed specifically by measurement of the maximum inspiratory pressure during crying (Pimax. Pressure-time index of the respiratory muscles (PTImus is a non-invasive method, which assesses the load to capacity ratio of the respiratory muscles. The objective of this study was to determine whether increased cACE activity in infants could be related to greater respiratory muscle strength and to investigate the potential association of cACE with PTImus measurements as well as the association of ACE genotypes with cACE activity and respiratory muscle strength in this population. Methods Serum ACE activity was assayed by using a UV-kinetic method. ACE genotyping was performed by polymerase chain reaction amplification, using DNA from peripheral blood. PTImus was calculated as (Pimean/Pimax × (Ti/Ttot, where Pimean was the mean inspiratory pressure estimated from airway pressure, generated 100 milliseconds after an occlusion (P0.1, Pimax was the maximum inspiratory pressure and Ti/Ttot was the ratio of the inspiratory time to the total respiratory cycle time. Pimax was the largest pressure generated during brief airway occlusions performed at the end of a spontaneous crying effort. Results A hundred and ten infants were studied. Infants with D/D genotype had significantly higher serum ACE activity than infants with I/I or I/D genotypes. cACE activity was significantly related to Pimax and inversely related to PTImus. No association between ACE genotypes and

  13. The Angiotensin Converting Enzyme Insertion/Deletion Polymorphism Modifies Exercise-Induced Muscle Metabolism.

    David Vaughan

    Full Text Available A silencer region (I-allele within intron 16 of the gene for the regulator of vascular perfusion, angiotensin-converting enzyme (ACE, is implicated in phenotypic variation of aerobic fitness and the development of type II diabetes. We hypothesised that the reportedly lower aerobic performance in non-carriers compared to carriers of the ACE I-allele, i.e. ACE-DD vs. ACE-ID/ACE-II genotype, is associated with alterations in activity-induced glucose metabolism and capillarisation in exercise muscle.Fifty-three, not-specifically trained Caucasian men carried out a one-legged bout of cycling exercise to exhaustion and/or participated in a marathon, the aim being to identify and validate genotype effects on exercise metabolism. Respiratory exchange ratio (RER, serum glucose and lipid concentration, glycogen, and metabolite content in vastus lateralis muscle based on ultra-performance lipid chromatography-mass spectrometry (UPLC-MS, were assessed before and after the cycling exercise in thirty-three participants. Serum metabolites were measured in forty subjects that completed the marathon. Genotype effects were assessed post-hoc.Cycling exercise reduced muscle glycogen concentration and this tended to be affected by the ACE I-allele (p = 0.09. The ACE-DD genotype showed a lower maximal RER and a selective increase in serum glucose concentration after exercise compared to ACE-ID and ACE-II genotypes (+24% vs. +2% and -3%, respectively. Major metabolites of mitochondrial metabolism (i.e. phosphoenol pyruvate, nicotinamide adenine dinucleotide phosphate, L-Aspartic acid, glutathione were selectively affected in vastus lateralis muscle by exercise in the ACE-DD genotype. Capillary-to-fibre ratio was 24%-lower in the ACE-DD genotype. Individuals with the ACE-DD genotype demonstrated an abnormal increase in serum glucose to 7.7 mM after the marathon.The observations imply a genetically modulated role for ACE in control of glucose import and oxidation in

  14. INCREASED ANGIOTENSIN II INDUCED HYPERTENSION AND INFLAMMATORY CYTOKINES IN MICE LACKING ANGIOTENSIN CONVERTING ENZYME N DOMAIN ACTIVITY

    Ong, Frank S.; Lin, Chentao X.; Campbell, Duncan J.; Okwan-Duodu, Derick; Chen, Xu; Blackwell, Wendell-Lamar B.; Shah, Kandarp H.; Gonzalez-Villalobos, Romer A.; Shen, Xiao Z.; Fuchs, Sebastien; Bernstein, Kenneth E.

    2011-01-01

    Angiotensin converting enzyme (ACE) is composed of the N- and C-terminal catalytic domains. To study the role of the ACE domains in the inflammatory response, N-KO and C-KO mice, models lacking one of the two ACE domains, were analyzed during angiotensin II-induced hypertension. At 2 weeks, N-KO mice have systolic blood pressures that averaged 173 ± 4.6 mm Hg, which is more than 25 mm Hg higher than the blood pressures observed in wild-type or C-KO mice (146 ± 3.2 and 147 ± 4.2 mm Hg). After ...

  15. Overexpression of angiotensin-converting enzyme in myelomonocytic cells enhances the immune response [version 1; referees: 3 approved

    Kenneth E. Bernstein

    2016-03-01

    Full Text Available Angiotensin-converting enzyme (ACE converts angiotensin I to the vasoconstrictor angiotensin II and thereby plays an important role in blood pressure control. However, ACE is relatively non-specific in its substrate specificity and cleaves many other peptides. Recent analysis of mice overexpressing ACE in monocytes, macrophages, and other myelomonocytic cells shows that these animals have a marked increase in resistance to experimental melanoma and to infection by Listeria monocytogenes or methicillin-resistant Staphylococcus aureus (MRSA. Several other measures of immune responsiveness, including antibody production, are enhanced in these animals. These studies complement a variety of studies indicating an important role of ACE in the immune response.

  16. Addition of Angiotensin Receptor Blockade or Mineralocorticoid Antagonism to Maximal Angiotensin-Converting Enzyme Inhibition in Diabetic Nephropathy

    Mehdi, Uzma F.; Adams-Huet, Beverley; Raskin, Philip; Vega, Gloria L.

    2009-01-01

    Aldosterone promotes glomerular and tubular sclerosis independent of angiotensin II in animal models of diabetic nephropathy. Most human studies testing the renoprotective benefit of adding an angiotensin receptor blocker or a mineralocorticoid receptor antagonist to a regimen based on inhibition of angiotensin-converting enzyme (ACE) used relatively low doses of ACE inhibitors. Furthermore, these studies did not determine whether antiproteinuric effects were independent of BP lowering. We conducted a double-blind, placebo-controlled trial in 81 patients with diabetes, hypertension, and albuminuria (urine albumin-to-creatinine ratio ≥300 mg/g) who all received lisinopril (80 mg once daily). We randomly assigned the patients to placebo, losartan (100 mg daily), or spironolactone (25 mg daily) for 48 wk. We obtained blood and urine albumin, urea, creatinine, electrolytes, A1c, and ambulatory BP at baseline, 24, and 48 wk. Compared with placebo, the urine albumin-to-creatinine ratio decreased by 34.0% (95% CI, −51.0%, −11.2%, P = 0.007) in the group assigned to spironolactone and by 16.8% (95% CI, −37.3%, +10.5%, P = 0.20) in the group assigned to losartan. Clinic and ambulatory BP, creatinine clearance, sodium and protein intake, and glycemic control did not differ between groups. Serum potassium level was significantly higher with the addition of either spironolactone or losartan. In conclusion, the addition of spironolactone, but not losartan, to a regimen including maximal ACE inhibition affords greater renoprotection in diabetic nephropathy despite a similar effect on BP. These results support the need to conduct a long-term, large-scale, renal failure outcomes trial. PMID:19926893

  17. Inhibitory Effect of Angiotensin-converting Enzyme Inhibitor Combined with Neda#atin on Hnmnu Nasopharyngeal Carcinoma CNE2 Cells%血管紧张素转换酶抑制剂联合奈达铂对鼻咽癌CNE2细胞的抑制作用

    莫正英; 李志玖; 梁清乐

    2009-01-01

    Objective To investigate the effect of angiotensin--converting enzyme inhibitor combined with nedaplatin on the growth of nasoph,taryngeal carcinoma CNE2 cells in vitro.Methods The effects of ACEI combined with nedaplatin on cell proliferation,cell cycle and VEGF expression of CNE2 were detected with MTr assay,flow cytometry,RT-PCR,Western blotting and ELISA,respectively.Results Neither NDP nor ACE-I had significant inhibitory effect on the CNE2 growth,while the combined application had significant inhibitory effect on the CNE2 growth VEGF expression.Conclusion The proliferation of CNE2 CoLdd be inhibited with the combination of ACE-I and NDP by inhibiting VEGF expression.%目的:研究血管紧张素转化酶抑制剂(ACE-I)联合奈达铂(NDP)在体外对鼻咽癌细胞生长的影响.方法:利用MTT比色法、流式细胞仪、RT-PCR、免疫印迹及酶联免疫等方法测定不同组(对照组、NDP组、ACE-I组、NDP+ACE-I组)对人鼻咽癌细胞CNE2生长、细胞周期及对血管内皮生长因子(VEGF)表达的影响.结果:单独NDP或ACE-I不能抑制CNE2细胞生长,联合应用能明显抑制CNE2细胞生长和VEGF的表达.结论:ACE-I和NDP联合抑制CNE2细胞增殖是通过抑制VEGF的表达实现的.

  18. Synthesis of 3-(2-Cinnamamidoethylsulfonyl)-thiazolidine-4-carboxylate Derivatives as Novel Angiotensin Converting Enzyme (ACE) Inhibitors%新型的3-(2-肉桂酰胺基乙磺酰基)噻唑烷-4-羧酸酯类血管紧张素转化酶抑制剂的合成

    武磊芳; 谢建伟; 代斌; 张洁; 马晓伟; 应雪; 焦艳丽

    2012-01-01

    以牛磺酸、半胱氨酸甲酯(乙酯)盐酸盐、4-取代肉桂酸等为原料,经过7步反应,合成了7个新型的3-(2-肉桂酰胺基乙磺酰基)噻唑烷-4-羧酸酯类衍生物,结构经1H NMR、13C NMR、MS和IR表征确证.7个目标化合物均未见文献报道,这类化合物可作为潜在的血管紧张素转化酶抑制剂(ACEIs).实验采用的合成方法简单易行,可作为一系列3-(2-肉桂酰胺基乙磺酰基)噻唑烷-4-羧酸酯类ACE抑制剂的合成通法.%Seven novel 3-(2-cinnamamidoethylsulfonyl)-thiazolidine-4-carboxylate derivatives were designed and synthesized in seven steps from taurine, L-cystein methyl ester (ethyl ester) hydrochloride,4-substituted cinnamic acid and other materials. The structures of these seven products were verified by 1H NMR,13C NMR,MS and IR. All of the target compounds were not reported in the literature and could be used as potential angiotensin converting enzyme (ACE) inhibitors. The method is simple, easy and can be used as a general method to synthesize a series of the thiazolidine-4-carboxylate derivatives.

  19. 为什么血管紧张素转化酶抑制剂能降低高血压患者死亡率?%Why can angiotensin-converting enzyme inhibitors reduce mortality in hypertension?

    廖玉华; 程龙献

    2012-01-01

    最新荟萃分析发现,肾素-血管紧张素(Ang)-醛固酮系统(RAAS)抑制剂能降低高血压患者死亡率,其治疗获益全部源于血管紧张素转化酶(ACE)抑制剂(ACEIs),而非血管紧张素受体拮抗剂(ARBs).RAAS可以归纳为2条轴:ACE-AngⅡ(1-8)-AT1受体轴和ACE2-Ang(1-7)-Mas受体轴,ACEIs对RAAS的2条轴均发挥良好作用,而ARBs主要作用于前者.各个指南推荐高血压相关心血管疾病治疗优先选择ACEIs,对不能够耐受者选择ARBs.我们应当重视ACEIs在高血压、冠心病、心肌梗死和心力衰竭防治中的应用,目的是降低心血管疾病患病率和死亡率的风险.%Latest meta-analysis has discovered that the renin-angiotensin-aldosterone system (RAAS) inhibitors can reduce mortality in hypertension, and the observed treatment effect resulted entirely from the class of ACE inhibitors rather than ARBs. RAAS may be summed up in two axes: ACE-Ang II (1-8)-ATi receptor axis and ACE2-Ang(l-7)-Mas receptor axis. ACE inhibitors developed fine effects in both axes, whereas ARBs was major effect on the former axis. All guidelines emphasized that ACE inhibitors should be started and continued indefinitely in all patients with hypertension-related cardiovascular diseases, and ARBs were recommended in patients who were intolerant to ACE-inhibitors. We should pay attention to ACE inhibitors used in patients with hypertension, coronary heart disease, myocardial infarction and heart failure, in order to reduce the long-term risk of cardiovascular morbidity and mortality.

  20. Influence of a history of arterial hypertension and pretreatment blood pressure on the effect of angiotensin converting enzyme inhibition after acute myocardial infarction. Trandolapril Cardiac Evaluation Study

    Gustafsson, F; Køber, L; Torp-Pedersen, C;

    1998-01-01

    inhibition after AMI complicated by left ventricular dysfunction may be of particular importance in patients with a history of arterial hypertension or a relatively high pretreatment blood pressure. However, further investigations are necessary to establish the clinical impact of these results.......OBJECTIVE: To evaluate the influence of a history of arterial hypertension and the level of pretreatment blood pressure on the efficacy of the angiotensin converting enzyme (ACE) inhibitor trandolapril on mortality and morbidity in patients with acute myocardial infarction (AMI) and left...... broad spectrum of potential confounders. Also, benefit from ACE inhibition increased with increasing blood pressure at the time of randomization. Significant interactions between benefit from ACE inhibition and hypertension history, and systolic and diastolic blood pressure were found. CONCLUSION: ACE...

  1. Differential regulation of renal angiotensin-converting enzyme (ACE) and ACE2 during ACE inhibition and dietary sodium restriction in healthy rats

    Hamming, I.; van Goor, H.; Turner, A. J.; Rushworth, C. A.; Michaud, A. A.; Corvol, P.; Navis, G.

    2008-01-01

    Angiotensin-converting enzyme (ACE) 2 is thought to counterbalance ACE by breakdown of angiotensin (Ang) II and formation of Ang(1-7). Both enzymes are highly expressed in the kidney, but reports on their regulation differ. To enhance our understanding of the regulation of renal ACE and ACE2, we inv

  2. Structure and Function of Angiotensin Converting Enzyme and Its Inhibitors%血管紧张素转换酶的结构功能及相关抑制剂

    赵钰岚; 许传莲

    2008-01-01

    血管紧张素转化酶(angiotensin convening enzyme,ACE,EC 3.4.15.1)是一种位于细胞膜上,依赖锌离子的羧二肽酶,催化水解十肽血管紧张素Ⅰ羧基末端两个氨基酸,生成具有血管收缩作用的八肽血管紧张素Ⅱ.ACE 在血压调节系统 renin -angiotensin system (RAS 系统)中具有重要作用,从 ACE 的结构功能、基因多态性及其抑制剂等方面进行了详细综述.发现体细胞ACE两个活性中心催化血管紧张素Ⅰ和缓激肽的机制不同,因此以体细胞ACE单个活性中心为靶点的研究,将会为研制开发副作用更少,安全性更高的ACE抑制剂提供新的途径.

  3. Altered angiotensin-converting enzyme and its effects on the brain in a rat model of Alzheimer disease

    HOU De-ren; WANG Yan; ZHOU Lin; CHEN Kun; TIAN Yi; SONG Zhi; BAO Juan; YANG Qi-dong

    2008-01-01

    Background Alzheimer disease (AD) is a neurodegenerative disease related to aging.At present,its pathological mechanisms remain unclear.Family members of the renin-angiotensin system (RAS) pray a role in neuronal plasticity,as well as formation of learning and memory,in this study,we explore the effects of altered angiotensin-converting enzyme (ACE),and investigate the possible mechanisms of perindopril,an ACE inhibitor,on brain structure and function in a rat model of AD,as well as the role that ACE plays in AD.Methods Sixty Sprague-Dawley rats were selected and randomly divided into 3 groups:control,AD,and perindopril.Each group consisted of 20 rats,with 10 rats for determining pathology,and the remaining 10 rats for quantifying ACE activity.The rat AD model was established by stereotactically injecting amyloid beta protein (A-beta) 1-42 into the right hippocampus.Learning and memory functions were tested using the Y-type electric maze.The number and morphology of abnormal neurons were determined by haematoxylin and eosin staining.Amyloid deposition was measured by Congo red staining.Finally,ACE activity was estimated by spectrophotometry.Results Compared with the control group,the number of times needed to escape electrical stimuli increased (23.70±3.13,P <0.001),the number of normal neurons in the CA1 region was reduced (density of 96.5±32.6/mm,Pgroup.In the perindopril group,the number of times needed to escape electrical stimuli decreased (18.50±3.66,P <0.001),the number of abnormal neurons increased (density of CA1 neurons was 180.8±28.5/mm,P <0.001),amyloid Conclusions ACE activity increased in the brains of AD rats.Perindopril improved learning and memory in AD rats,which correlated with decreased ACE activity and delayed AD pathogenesis.

  4. The angiotensin-converting enzyme gene insertion–deletion polymorphism in a white British patient cohort with obstetric cholestasis

    Müllenbach, Roman; Tetlow, Natasha; Bennett, Amanda; Pipkin, Fiona Broughton; Morgan, Linda; Williamson, Catherine

    2009-01-01

    The DD genotype of the angiotensin-converting enzyme (ACE) gene is over-represented in Finnish patients with obstetric cholestasis (OC). The purpose of this study was to establish whether this genotype is associated with cholestasis in UK cases. In a retrospective case-control study, we determined the ACE insertion/deletion frequencies in 166 British cases and 100 control women by polymerase chain reaction analysis. No significant difference in allele frequencies was found between these groups, but allele frequencies differed significantly between Finnish and UK OC cases (P = 0.0005). The prevalence of the DD genotype is lower in UK cases than in controls (χ2 [1 d.f.] = 4.32, P = 0.05) and the odds ratio for OC associated with the DD genotypeis 0.54, 95% confidence interval 0.30–0.97. In contrast to Finnish OC cases, the DD genotype of the ACE is not increased in UK cases.

  5. Angiotensin-converting enzyme and angiotensin II receptor subtype 2 genotypes in type 1 diabetes and severe hypoglycaemia requiring emergency treatment: a case cohort study

    Pedersen-Bjergaard, Ulrik; Nielsen, Søren L; Akram, Kamran;

    2009-01-01

    AIMS: In type 1 diabetes, individual susceptibility to severe hypoglycaemia is likely to be influenced by genetic factors. We have previously reported an association of the deletion (D-) allele of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and the A-allele of th...

  6. KARAKTERISTIK FISIK, KIMIA, MIKROBIOLOGI WHEY KEFIR DAN AKTIVITASNYA TERHADAP PENGHAMBATAN ANGIOTENSIN CONVERTING ENZYME (ACE [Physical, Chemical and Microbiological Characteristics of Whey Kefir and Its Angiotensin Converting Enzyme (ACE Inhibitory Activity

    Andi Febrisiantosa*

    2013-12-01

    Full Text Available This study was conducted to evaluate the characteristics of whey-based kefir products and their activity to inhibit the angiotensin converting enzyme (ACE. Kefir was produced by using many types of whey, namely SK: skim milk based kefir (control; WK: gouda cheese whey based kefir; and WKB: commercial whey powder based kefir. The experimental design was a completely randomized design. Each treatment was conducted in triplicates. Kefirs were evaluated for physical and chemical properties (pH, total titratable acidity, viscosity, protein, fat, lactose, and alcohol, microbiological (lactic acid bacteria and yeast population, peptide concentration, ACE inhibition, IC50 and Inhibition Efficiency Ratio (IER. The results showed that the types of whey used for kefir productions significantly affected the physical and chemical characteristics of the products (p0.05. The peptide concentration and ACE inhibitory activity of WK, 1.54±0.02 mg/mL and 73.07±0.91%, was significantly higher (p0.05 from the control (47.19±0.09% per mg/mL but was significantly higher (p<0.05 than that of WKB (45.75±0.18% per mg/mL. This research indicated that whey kefir is a potential source of bioactive peptide for antihypertention agent.

  7. Variations in angiotensin-converting enzyme gene insertion/deletion polymorphism in Indian populations of different ethnic origins

    M A Qadar Pasha; Amjad P Khan; Ratan Kumar; Rekh B Ram; Surinder K Grover; Kaushal K Srivastava; William Selvamurthy; Samir K Brahmachari

    2002-02-01

    The pattern of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in the Indian population is poorly known. In order to determine the status of the polymorphism, young unrelated male army recruits were screened. The population had cultural and linguistic differences and lived in an environment that varied significantly from one region to another. Analysis of the genotype, showed higher frequency of the insertion allele in four of the five groups i.e. I allele frequency was significantly higher ( < 0.05) in Dogras, Assamese and Kumaonese. The deletion allele frequency was comparatively higher in the fifth group that belonged to Punjab. A correlation was observed between the genotype and enzyme activity. Involvement of a single D allele in the genotype enhanced the activity up to 37.56 ± 3.13%. The results suggested ethnic heterogeneity with a significant gene cline with higher insertion allele frequency. Such population-based data on various polymorphisms can ultimately be exploited in pharmacogenomics.

  8. Molecular-genetic risk assessement of determining angiotensin-converting enzyme hyperactivity in hemorrhagic fever with renal syndrome

    Ildar R. Minniakhmetov

    2012-09-01

    Full Text Available The present study was designed to investigate changes in angiotensin-converting enzyme (ACE blood activity and angiotensin II type 1 receptor gene polymorphism as a possible disease predictor in hemorrhagic fever with renal syndrome (HFRS. Four hundred and nine patients (346 males and 63 females with HFRS serologic confirmation were enrolled in the study. Their age ranged from 15 to 65 years. ACE blood activity was assessed kinetically using the Bühlmann (Switzerland kit. Peripheral blood genomic DNA was isolated by a phenol-chloroform extraction. The genotyping of DNA loci was done using a polymerase chain reaction of DNA synthesis. Statistically, ACE blood activity was significantly higher throughout the entire HFRS course with diverse severity apart from the feverish phase of moderate-to-severe uncomplicated disease forms. *A1166 and *C1166 alleles, *A1166/*A1166 and *C1166/*C1166 genotypes of angiotensin II type 1 receptor gene were not associated with HFRS severity. The results of this study indicate that high ACE activity has not adaptive characteristics due to abnormalities in angiotensin II reception. It is an adequate metabolic response of the body to endotheliotropic virus activity.

  9. Myocardial perfusion in type 2 diabetes with left ventricular hypertrophy: normalisation by acute angiotensin-converting enzyme inhibition

    The purpose of this study was to assess whether acute angiotensin-converting enzyme (ACE) inhibition would improve myocardial perfusion and perfusion reserve in a subpopulation of normotensive patients with diabetes and left ventricular hypertrophy (LVH), both independent risk factors of coronary disease. Using positron emission tomography (PET), we investigated the response of regional myocardial perfusion to acute ACE inhibition with i.v. infusion of perindoprilat (vs saline infusion as control, minimum interval 3 days) in 12 diabetic patients with LVH. Myocardial perfusion was quantified with PET using nitrogen-13 ammonia infused at rest and during dipyridamole hyperaemia. Twelve healthy control subjects were included in the study, five of whom were also studied with perindoprilat. Mean blood pressure in normo-albuminuric, asymptomatic patients was 123±7/65±9 mmHg. Compared with controls, maximal perfusion was reduced in patients (1.8±0.6 vs 2.5±1.0 ml min-1 g-1; P-1 g-1, P<0.01). In the five control subjects both resting and hyperaemic perfusion remained unchanged during perindoprilat infusion. It is concluded that acute ACE inhibition with perindoprilat improves maximal achieved myocardial perfusion in non-hypertensive patients with diabetes and LVH. (orig.)

  10. Efficient Replication of Severe Acute Respiratory Syndrome Coronavirus in Mouse Cells Is Limited by Murine Angiotensin-Converting Enzyme 2

    Li, Wenhui; Greenough, Thomas C.; Moore, Michael J.; Vasilieva, Natalya; Somasundaran, Mohan; Sullivan, John L.; Farzan, Michael; Choe, Hyeryun

    2004-01-01

    Replication of viruses in species other than their natural hosts is frequently limited by entry and postentry barriers. The coronavirus that causes severe acute respiratory syndrome (SARS-CoV) utilizes the receptor angiotensin-converting enzyme 2 (ACE2) to infect cells. Here we compare human, mouse, and rat ACE2 molecules for their ability to serve as receptors for SARS-CoV. We found that, compared to human ACE2, murine ACE2 less efficiently bound the S1 domain of SARS-CoV and supported less-efficient S protein-mediated infection. Rat ACE2 was even less efficient, at near background levels for both activities. Murine 3T3 cells expressing human ACE2 supported SARS-CoV replication, whereas replication was less than 10% as efficient in the same cells expressing murine ACE2. These data imply that a mouse transgenically expressing human ACE2 may be a useful animal model of SARS. PMID:15452268

  11. Relationship between angiotensin-converting enzyme gene polymorphism and cardio-brain complications in patients with NIDDM (type 2 diabetes mellitus)

    Objective: To investigate the relationship between angiotensin-converting enzyme gene polymorphism and cardio-brain complications in patients with NIDDM. Methods: The angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism in 174 patients with NIDDM and 62 controls were examined with PCR. Results: ACE gene I/D polymorphism was closely related to coronary heart disease (angina, cardiac infarction) and cerebral infarction in diabetic patients but not with hypertension. Plasma renin activity and plasma angiotensin II levels in complicated diabetic patients with ACE D/D gene were significantly higher than those in the controls (p < 0.01). Their aldosterone and endothelin contents were not significantly different. Conclusion: Examination of ACE gene I/D polymorphism was useful for the primary prevention of cardio-brain complications in diabetic patients and helpful in the early diagnosis and therapy of coronary heart disease and cerebral infarction

  12. [The role of angiotensin-converting enzyme gene I/D polymorphism in development of metabolic disorders in patients with cardiovascular pathology].

    Vynohradova, S V

    2005-01-01

    The role of angiotensin-converting enzyme (ACE) gene I/D polymorphism in development of cardiovascular pathology (CVP), metabolic syndrom and insulin-independent diabet associated with such metabolic disorders as glucose intolerance and hyperglicemia, intolerance to insulin and hyperinsulinemia, dyslipiproteinemia (DLP) and obesity is discussed. Most of authors consider D-allel and DD genotype to be assosiated with development of DLP and such CVP as ishemic heart disease and myocardial infarction. PMID:16018179

  13. Angiotensin-Converting Enzyme (ACE) 2 Overexpression Ameliorates Glomerular Injury in a Rat Model of Diabetic Nephropathy: A Comparison with ACE Inhibition

    Liu, Chun Xi; Hu, Qin; Yan WANG; Zhang, Wei; Ma, Zhi Yong; Feng, Jin Bo; Wang, Rong; Wang, Xu Ping; Dong, Bo; Gao, Fei; Zhang, Ming Xiang; Zhang, Yun

    2010-01-01

    The reduced expression of angiotensin-converting enzyme (ACE) 2 in the kidneys of animal models and patients with diabetes suggests ACE2 involvement in diabetic nephrology. To explore the renoprotective effects of ACE2 overexpression, ACE inhibition (ACEI) or both on diabetic nephropathy and the potential mechanisms involved, 50 Wistar rats were randomly divided into a normal group that received an injection of sodium citrate buffer and a diabetic model group that received an injection of 60 ...

  14. Angiotensin-converting enzyme inhibition in patients with coronary artery disease and preserved left ventricular function : Ischemia Management with Accupril post-bypass graft via inhibition of angiotensin-converting enzyme (IMAGINE) compared with the other major trials in coronary- artery disease

    van Gilst, WH; Warnica, JW; Baillot, R; Johnstone, D; Calciu, CD; Block, P; Myers, MG; Chocron, S; Rouleau, JL

    2006-01-01

    It has been hypothesized that angiotensin-converting enzyme (ACE) inhibition, independent from its effect on ventricular function and blood pressure, could affect the atherosclerotic process and reduce the incidence of ischemic events and its complications. Several large clinical outcome trials were

  15. Adeno-Associated Virus Overexpression of Angiotensin-Converting Enzyme-2 Reverses Diabetic Retinopathy in Type 1 Diabetes in Mice.

    Dominguez, James M; Hu, Ping; Caballero, Sergio; Moldovan, Leni; Verma, Amrisha; Oudit, Gavin Y; Li, Qiuhong; Grant, Maria B

    2016-06-01

    Angiotensin-converting enzyme (ACE)-2 is the primary enzyme of the vasoprotective axis of the renin angiotensin system that regulates the classic renin angiotensin system axis. We aimed to determine whether local retinal overexpression of adenoassociated virus (AAV)-ACE2 prevents or reverses diabetic retinopathy. Green fluorescent protein (GFP)-chimeric mice were generated to distinguish resident (retinal) from infiltrating bone marrow-derived inflammatory cells and were made diabetic using streptozotocin injections. Retinal digestion using trypsin was performed and acellular capillaries enumerated. Capillary occlusion by GFP(+) cells was used to measure leukostasis. Overexpression of ACE2 prevented (prevention cohort: untreated diabetic, 11.3 ± 1.4; ACE2 diabetic, 6.4 ± 0.9 per mm(2)) and partially reversed (reversal cohort: untreated diabetic, 15.7 ± 1.9; ACE2 diabetic, 6.5 ± 1.2 per mm(2)) the diabetes-associated increase of acellular capillaries and the increase of infiltrating inflammatory cells into the retina (F4/80(+)) (prevention cohort: untreated diabetic, 24.2 ± 6.7; ACE2 diabetic, 2.5 ± 1.6 per mm(2); reversal cohort: untreated diabetic, 56.8 ± 5.2; ACE2 diabetic, 5.6 ± 2.3 per mm(2)). In both study cohorts, intracapillary bone marrow-derived cells, indicative of leukostasis, were only observed in diabetic animals receiving control AAV injections. These results indicate that diabetic retinopathy, and possibly other diabetic microvascular complications, can be prevented and reversed by locally restoring the balance between the classic and vasoprotective renin angiotensin system. PMID:27178803

  16. A systematic review: effect of angiotensin converting enzyme inhibition on left ventricular volumes and ejection fraction in patients with a myocardial infarction and in patients with left ventricular dysfunction

    Abdulla, Jawdat; Barlera, Simona; Latini, Roberto;

    2006-01-01

    BACKGROUND AND AIM: To summarize and quantify results of echocardiographic studies examining the effect of angiotensin converting enzyme (ACE) inhibition on left ventricular remodelling in patients with acute myocardial infarction (MI) and in patients with left ventricular systolic dysfunction (L...

  17. Serum levels of renin, angiotensin-converting enzyme and angiotensin II in patients treated by surgical excision, propranolol and captopril for problematic proliferating infantile haemangioma.

    Sulzberger, L; Baillie, R; Itinteang, T; de Jong, S; Marsh, R; Leadbitter, P; Tan, S T

    2016-03-01

    The role of the renin-angiotensin system (RAS) in the biology of infantile haemangioma (IH) and its accelerated involution induced by β-blockers was first proposed in 2010. This led to the first clinical trial in 2012 using low-dose captopril, an angiotensin-converting enzyme (ACE) inhibitor, demonstrating a similar response in these tumours. This study aimed to compare serial serum levels of the components of the RAS in patients before and after surgical excision, propranolol or captopril treatment for problematic proliferating IH. Patients with problematic proliferating IH underwent measurements of serum levels of plasma renin activity (PRA), ACE and angiotensin II (ATII) before, and 1-2 and 6 months following surgical excision, propranolol or captopril treatment. This study included 27 patients undergoing surgical excision (n = 8), propranolol (n = 11) and captopril (n = 8) treatment. Treatment with either surgical excision or propranolol resulted in significant decrease in the mean levels of PRA. Surgical excision or captopril treatment led to significant decline in the mean levels of ATII. All three treatment modalities had no significant effect on the mean levels of ACE. This study demonstrates the effect of surgical excision, propranolol and captopril treatment in lowering the levels of PRA and ATII, but not ACE, supporting a mechanistic role for the RAS in the biology of IH. PMID:26612192

  18. Bioassay-guided preparative separation of angiotensin-converting enzyme inhibitory C-flavone glycosides from Desmodium styracifolium by recycling complexation high-speed counter-current chromatography.

    Zhang, Ying-Qi; Luo, Jian-Guang; Han, Chao; Xu, Jin-Fang; Kong, Ling-Yi

    2015-01-01

    A new strategy of the convergence of high-speed counter-current chromatography (HSCCC) and bioactive assay technique was developed for rapidly screening and separating the angiotensin-converting enzyme (ACE) inhibitors from the aerial parts of Desmodium styracifolium. Bioactivity-guided fractionation of the crude extract was first established to target the bioactive fractions based on HSCCC coupled with in vitro ACE inhibitory assay. Subsequently, the bioactive fractions were further separated by the recycling complexation HSCCC respectively, using 0.10 mol/L copper sulfate in the lower phase of two-phase solvent system composed of n-butanol/water (1:1, v/v). Five C-glycosylflavones, vicenin 2 (1), carlinoside (2), vicenin 1 (3), schaftoside (4) and vicenin 3 (5), were successfully obtained. Their chemical structures were identified using ESI-MS and NMR. All the isolates showed in vitro ACE inhibitory activity with the IC50 values between 33.62 and 58.37 μM. The results demonstrated that the established method was proposed as an excellent strategy to systematically screen and purify active compounds from traditional Chinese medicines. PMID:25459924

  19. Green asparagus (Asparagus officinalis) prevented hypertension by an inhibitory effect on angiotensin-converting enzyme activity in the kidney of spontaneously hypertensive rats.

    Sanae, Matsuda; Yasuo, Aoyagi

    2013-06-12

    Green asparagus (Asparagus officinalis) is known to be rich in functional components. In the present study, spontaneously hypertensive rats (SHR) were used to clarify whether green asparagus prevents hypertension by inhibition of angiotensin-converting enzyme (ACE) activity. Six-week-old male SHR were fed a diet with (AD group) or without (ND group) 5% asparagus for 10 weeks. Systolic blood pressure (SBP) (AD: 159 ± 4.8 mmHg, ND: 192 ± 14.7 mmHg), urinary protein excretion/creatinine excretion, and ACE activity in the kidney were significantly lower in the AD group compared with the ND group. Creatinine clearance was significantly higher in the AD group compared with the ND group. In addition, ACE inhibitory activity was observed in a boiling water extract of asparagus. The ACE inhibitor purified and isolated from asparagus was identified as 2″-hydroxynicotianamine. In conclusion, 2″-hydroxynicotianamine in asparagus may be one of the factors inhibiting ACE activity in the kidney, thus preventing hypertension and preserving renal function. PMID:23647085

  20. Peptides Derived from Rhopilema esculentum Hydrolysate Exhibit Angiotensin Converting Enzyme (ACE) Inhibitory and Antioxidant Abilities

    Jun Li; Qian Li; Jingyun Li; Bei Zhou

    2014-01-01

    Jellyfish (Rhopilema esculentum) was hydrolyzed using alcalase, and two peptides with angiotensin-I-converting enzyme (ACE) inhibitory and antioxidant activities were purified by ultrafiltration and consecutive chromatographic methods. The amino acid sequences of the two peptides were identified as VKP (342 Da) and VKCFR (651 Da) by electrospray ionization tandem mass spectrometry. The IC50 values of ACE inhibitory activities of the two peptides were 1.3 μM and 34.5 μM, respectively. Molecula...

  1. Polymorphisms of angiotensin-converting enzyme 2 gene confer a risk to lone atrial fibrillation in Chinese male patients

    WANG Shu-xia; TAO Tao; FU Zhi-qing; XIE Xiang-zhu; WANG Hao; WANG Yu-tang

    2013-01-01

    Background Growing epidemiologic evidence has indicated that genetics can predispose individuals to the occurrence of lone atrial fibrillation (AF).The angiotensin-converting enzyme 2 (ACE2) gene has been established to be associated with hypertension and left ventricular hypertrophy.The objective of our study was to investigate the association of ACE2 gene polymorphisms with lone AF.Methods A total of 265 consecutive lone AF patients and 289 healthy controls were successfully investigated.The polymorphisms rs2106809 and rs2285666 were genotyped by polymerase chain reaction (PCR) and direct sequencing.A Logistic regression model was used to determine the odds ratio (OR) and 95% confidence intervals (CI) of variations of ACE2 for lone AF.Results The T allele of rs2106809 conferred an increased risk for lone AF (OR 1.24,95% CI 1.01-1.52,P=0.03) in males after adjustment for conventional risk factors.SNP at rs2285666 in males was not significantly different between AF patients and controls.No association was found between the two polymorphisms in the female population with lone AF.After (36.3±4.5) months of follow-up,the end point data were obtained:death (cardiac and noncardiac),ischemic stroke,and heart failure.In the male subgroup,the associations between rs2106809 T male carriers and combined end points including ischemic stroke,heart failure,and death in our study were of significance (OR 3.6,95% CI 1.0-13.1,P=0.04).Conclusions The results indicate that polymorphism at ACE2 gene is associated with male lone AF in a Chinese Han population.Lone AF males who carry the rs2106809 T allele are associated with adverse cardiac events.

  2. Angiotensin-converting enzyme gene I/D genotype affected metoprolol-induced reduction in 24-hour average heart rate

    LIU Li-wei; LIU Hong; CHEN Guo-liang; HUANG Yi-ling; HAN Lu-lu; XU Zhi-min; JIANG Xiong-jing; LI Yi-shi

    2010-01-01

    Background Genetic factors can influence antihypertensive response to metoprolol, and many studies focused on the relationship between the genotype in β1-adrenergic receptor and blood pressure (BP), little was known about the association of angiotensin-converting enzyme (ACE) genotype with the therapeutic result of metoprolol. The present study aimed to investigate whether the ACE gene insertion (I) / deletion (D) polymorphism Is related to the response to metoprolol in Chinese Han hypertensive patients.Methods Ninety-six patients with essential hypertension received metoprolol (100 mg once daily) as monotherapy for 8 weeks. Twenty-four hours ambulatory blood pressure monitoring and dynamic electrocardiogram were performed before and after treatment. Genotyping analysis was performed using PCR. The association of the ACE gene I/D polymorphism with variations in BP and heart rate (HR) was observed after the 8-week treatment.Results The patients with ACE gene II polymorphism showed greater reduction in 24-hour average HR than those with ID or DD polymorphisms (P=0.045), no effect of this genotype on the reduction in seating HR or in BP was observed. After adjusting for age, gender, body mass index, BP and HR at baseline, the ACE gene I/D polymorphism was still an independent predictor for variations in 24-hour average HR.Conclusions The II polymorphism in ACE gene could be a candidate predictor for greater reduction in 24-hour average HR in Chinese Han hypertensive patients treated by metoprolol. Greater benefits would be obtained by patients with II polymorphism from the treatment with metoprolol. Larger studies are warranted to validate this finding.

  3. Association of Angiotensin-Converting Enzyme (ACE Gene Polymorphism with Inflammation and Cellular Cytotoxicity in Vitiligo Patients.

    Laila Rashed

    Full Text Available Vitiligo is a disorder with profound heterogeneity in its aetio-pathophysiology. Angiotensin converting enzyme (ACE plays an important role in the physiology of the vasculature, blood pressure and inflammation. An insertion/deletion (I/D polymorphism of the ACE gene was reported be associated with the development of vitiligo.Our aim was to evaluate the ACE I/D polymorphism in vitiligo patients and controls. Our second aim was to find a possible association between ACE gene polymorphism and inflammatory mediators (as interleukin (IL-6 and/or cellular cytotoxicity induced by serum nitrite (as a breakdown product of the cytotoxic nitric oxide in vitiligo patients.This case-control study included 74 vitiligo patients and 75 apparently healthy controls. The distribution of ACE gene I/D genotype was investigated using PCR. Serum ACE, IL-6 and nitrite were measured by colorimetric method, ELISA and Griess assay respectively.The ACE allele frequency was significantly different between vitiligo patients and healthy controls (P = 0.026. However there was no significant difference between the ACE genotyping frequency in both groups (P = 0.115. There were statistically significant higher VIDA score (P = 0.007, and serum IL-6 (P < 0.001 in patients with the DD genotype when compared to other genotypes. Serum nitrite in patients with the DD genotype was significantly higher (P = 0.007 when compared to patients with II genotype. Serum levels of ACE, IL-6 and nitrite in vitiligo patients were statistically significantly higher than those in controls.As a conclusion, ACE gene polymorphism might grant susceptibility to develop vitiligo. Serum IL-6 and nitrite levels might have an important role in the pathogenesis of vitiligo. Targeting these two factors might have an implication in the treatment of some resistant cases.

  4. Left ventricular hypertrophy in relation to systolic blood pressure and the angiotensin converting enzyme I/D polymorphism in Chinese

    Alexander P. Headley; Yan Li; Yi Zhang; Ji-Yong Ge; Qi-Fang Huang; Ji-Guang Wang

    2009-01-01

    Objective There is little population-based data on the prevalence and the environmental or genetic determinants of left ventricular hypertrophy (LVH) in China. The purpose of this paper is to study LVH in relation to systolic blood pressure and the angiotensin converting enzyme (ACE) insertion/deletion(I/D) polymorphism in Chinese. Methods We recorded 12-lead ECG (CardioSoft, v4.2) in 1365 residents in the Jingning County, Zhejiang Province, China. LVH was defined according to the gender-specific Sokolow-Lyon and Comell product ECG criteria. Results Regardless of whether the Sokolow-Lyon or Comell product ECG criteria was used, the prevalence of LVH (20.7% and 4.8%, respectively) significantly (P<0.0001) increased with male gender (odds ratio [OR] 2.33 and 7.15) and systolic blood pressure (per 10 mm Hg increase, OR 1.46 and 1.33). If the Sokolow-Lyon criteria was used, the prevalence of LVH was also influenced by alcohol intake (OR 1.44, P=0.03) and body mass index (OR 0.83, P=0.0005). The association between the Sokolow-Lyon voltage amplitude and the ACE I/D polymorphism was dependent on antihypertensive therapy (P=0.01). In 1262 untreated subjects, but not 103 patients on antihypertensive medication, the ACE DD compared with Ⅱ subjects had significantly higher Sokolow-Lyon voltage amplitudes (29.8±0.6 vs. 28.0±20.5 mV, P=0.02) and higher risk of LVH (OR 1.74, 95% CI: 1. 12-2.69, P=0.01). Conclusion LVH is prevalent in Chinese, and is associated with systolic blood pressure and the ACE D allele. The genetic association might be modulated by antihypertensive therapy.

  5. Effect of angiotensin converting enzyme gene I/D polymorphism in patients with metabolic syndrome in North Indian population

    Gaurav Mittal; Vibhanshu Gupta; Shahzad F Haque; Anwer S Khan

    2011-01-01

    Background Numerous studies have investigated the effect of angiotensin converting enzyme (ACE) gene I/D polymorphism and various cardiovascular risk factors in different populations with varied results. Currently, the association of ACE gene polymorphism with metabolic syndrome has not been studied in North Indians. While studies assessing the effect with polymorphism on each of the components of metabolic syndrome separately are present, data regarding the metabolic syndrome per se are sparse. The present study evaluated the effect of ACE gene I/D polymorphism in patients with metabolic syndrome in North Indian population at a tertiary care centre.Methods Fifty subjects, with thirty cases of metabolic syndrome (NCEP/ATP Ⅲ guidelines, 2004) and twenty age and gender matched healthy controls were chosen. Detailed history was reviewed and clinical examination of the subjects was carried out. Relevant investigations including blood glucose (fasting and post prandial), blood urea, serum creatinine and serum lipids were done. DNA of cases and controls was analysed for I/D polymorphism using polymerase chain reaction.Results D/D genotype was more frequent in patients with metabolic syndrome as compared with healthy controls (P<0.05). Systolic blood pressure (SBP) and diastolic blood pressure (DBP) was significantly higher in the D/D genotype than I/D and I/I genotypes (P <0.05). Our study also showed positive association between obesity, fasting blood glucose and ACE gene polymorphism while no association was found with triglycerides and high density lipoprotein cholesterol.The I/I group was significantly associated with waist circumference and fasting blood glucose (P <0.05).Conclusion Our study clearly showed that metabolic syndrome was associated with ACE gene polymorphism.However due to less number of subjects in the study further studies are needed to corroborate our results.

  6. Diagnostic usefulness of bronchoalveolar lavage, Ga scintigraphy and serum angiotensin converting enzyme activity in granulomatous lung disease

    Cellular components of bronchoalveolar lavage (BAL) fluid were studied in 26 sarcoid patients, 8 patients with farmer's lung, 10 healthy controls and 10 control patients. The investigations by Ga scintigraphy or transbronchial lung biopsy (TBLB) and measurement of serum angiotensin converting enzyme (SACE) activity were also carried out in 21 sarcoid patients and 8 patients with farmer's lung. 1) Percentage of foamy cells in alveolar ma crophage fraction, percentage of lymphocytes and number of mast cells were increased significantly in BLA fluid from patients with farmer's lung as compared with that from sarcoid patients. Analysis of cellular component of BAL flu id is useful for differential diagnosis of these diseases. 2) Granulomatous lung lesions were frequently observed in specimens obtained by TBLB from patients with sarcoidosis and farmer's lung who showed abnormal Ga uptake in lung. In contrast, there was no significant difference in percentage of lymphocytes in BAL fluid between patients whose pulmonary Ga uptake was positive and those in whom pulmonary Ga uptake was negative. To investigate the mechanism of pulmonary Ga accumulation in granulomatous lung disease, BAL was performed in 2 sarcoid patients and 3 patients with farmer's lung at 48 to 72 hrs after Ga injection. The radioactivity in cell fractions was evaluated at 96 hrs after Ga injection. Most of the radioactivity was found in macrophages, with little in lymphocytes. Pulmonary Ga uptake in patients with sarcoidosis and farmer' s lung reflects granuloma formation or accumulation of activated macrophages in lung, but not the intensity of T-cell alveolitis. 3) Some relationship among SACE, granulomatous lung lesions in specimens obtained by TBLB and abnormal Ga accumulation in lung or hilar lymphnodes in sarcoid patients was observed, suggesting that SACE might reflect the degree of granuloma formation in sarcoidosis. (J.P.N.)

  7. AT1a Receptor Has Interacted with Angiotensin-converting Enzymes 2 mRNA Expression in Mouse Brainstem

    Zhanyi Lin; Shuguang Lin

    2008-01-01

    Objectives To examine in vivo interactions between angiotensin Ⅱ(Ang Ⅱ) AT1a receptor (AT1aR),angiotensin-converting enzymes (ACE) and ACE2 using small hairpin RNA (shRNA) gene-silencing methods in mice brainstem nucleus ttactus solitarius (NTS).Methods C57BL mice (n=8) were used as animal model.Method of microinjection in the nucleus of NTS was adopted.After ten days,mice were killed and their brain tissue were fixed and sectioned.The expression levels of AT1 aR,ACE and ACE2 mRNA at both sides of NTS were examined by in situ hybridization.Based on compared t-test,the changing for mRNA expression was examined.Results After the expression of AT1aR mRNA was significantly inhibited (61.6%±6.8% ) by AT1aR-shRNA,it was associated with decreases in ACE2 mRNA expression from (1.05±0.12) μCi/mg to (0.74±0.09) μCi/mg (29.0%±14.5%,P<0.01) on the same side of the brainstem.ACE mRNA expression was consistent at both sides (0.50 μCi/mg±0.09 μCi/mg and 0.53 μCi/mg±0.08 μCi/mg),with insignificant difference (P>0.05).Condusions The gene silencing result showed that there were interactions between brainstem AT1aR and ACE2.ACE mRNA expression was not altered by RNA interference treatment at AT1aR.

  8. A Meta-analysis on the correlation between the polymorphism of angiotensin converting enzyme gene and hypertrophic cardiomyopathy

    Ling CHEN

    2014-01-01

    Full Text Available Objective To systematically investigate the correlation between the polymorphism of angiotensin converting enzyme (ACE gene I/D and hypertrophic cardiomyopathy. Methods The databases, such as PubMed, Embase, OVID, Web of Science, Cochrane library, CNKI, WanFang Data and VIP, were searched to collect the studies on the correlation between ACE I/D polymorphism and hypertrophic cardiomyopathy susceptibility. Studies that met the inclusion criteria were Meta-analyzed using Stata 11.0 software. Results Fifteen articles were collected including 1114 cases and 1648 controls. The Meta-analysis indicated that there was significant correlation between the 4 models of ACE I/D polymorphism and hypertrophic cardiomyopathy susceptibility [D vs I: OR=1.49, 95%CI (1.20, 1.84; DD vs (ID+II: OR=1.56, 95%CI (1.17, 2.08; (DD+ID vs II: OR=1.76, 95%CI (1.30, 2.38; DD vs II: OR=2.20, 95%CI (1.44, 3.37]. In subgroup analysis, the significant difference existed in Asian population, but no significance was found in European population (P<0.05. Conclusions There is a positive correlation between hypertrophic cardiomyopathy and ACE I/D polymorphism in population, and D allele and DD genotype are likely to be the risk factors of hypertrophic cardiomyopathy. But such correlation does not exist in European population. DOI: 10.11855/j.issn.0577-7402.2013.12.07

  9. Angiotensin-converting enzyme 2 activation protects against pulmonary arterial hypertension through improving early endothelial function and mediating cytokines levels

    LI Gang; XU Yu-lin; LING Feng; LIU Ai-jun; WANG Dong; WANG Qiang; LIU Ying-long

    2012-01-01

    Background Increasing evidences indicate that an activated renin-angiotensin system (RAS) causes an imbalance between the vasoconstrictive and vasodilator mechanisms involving the pulmonary circulation leading to the development of pulmonary arterial hypertension (PAH).Angiotensin-converting enzyme 2 (ACE2),a primary component of the vasoprotective axis in RAS,is recently identified that it has regulatory actions in lung pathophysiology,but the mechanism in these processes is uncertain yet.Methods Severe PAH was induced by monocrotaline injection one week following pneumonectomy in rats.The activation of ACE2 by continuous injection of resorcinolnaphthalein was studied by real time-polymerase chain reaction (RT-PCR),Western blotting and fluorogenic peptide assay.Endothelial functions were evaluated by the response to acetylcholine and cytokines were measured by RT-PCR seven days after monocrotaline injection.The PAH-related hemodynamics and pathological changes were examined at day 21 when severe PAH was completely established.Results Resorcinolnaphthalein caused significant activation of ACE2 in both normal and diseased rats in 7 days after treatment.The pulmonary arterial pressure (PAP) started to increase at least 7 days after monocrotaline injection,and the rats developed severe PAH in 21 days with high PAP,right ventricular hypertrophy and neointimal formation.Treatment with resorcinolnaphthalein prevented these features.Resorcinolnaphthalein caused an improved endothelia-dependent vasorelaxation and decrease in proinflammatory cytokines (tumor necrosis factor (TNF)-α,monocyte chemoattractant protein-1 (MCP-1),interleukin (IL)-6) and increase in anti-inflammatory cytokine IL-10 in the early stage of the pathogenesis.Conclusions These results demonstrated that activation of ACE2 by continuous injection of resorcinolnaphthalein prevented the development of PAH through improving early endothelial dysfunction and mediating the level of proinflammatory and anti

  10. Expression of Extracellular Signal-regulated Kinase and Angiotensin-converting Enzyme in Human Atria during Atrial Fibrillation

    戴友平; 王祥; 曹林生; 杨杪; 邬堂春

    2004-01-01

    Summary: In order to investigate the changes in the expression of extracellular signal-regulated kinase (ERK1/ERK2) and angiotensin-converting enzyme (ACE) in the patients with atrial fibrillation (AF), 52 patients with rheumatic heart diseases were examined. Nineteen patients had chronic persistent AF (AF≥6 months, CAF), 12 patients had paroxymal AF (PAF) and 21 patients had no history of AF. The ERK expression was detected at the mRNA level by reverse transcription polymerase chain reaction, at the protein level by Western blotting and at atrial tissue level by immunohistochemistry. ERK-activating kinases (MEK1/2) and ACE were determined by Western blotting techniques. The expression of ERK2-mRNA was increased in the patients with CAF (74±19 U vs sinus rhythm: 32±24 U, P<0.05). Activated ERK1/ERK2 and MEK1/2 were increased to more than 150 % in the patients with AF compared to those with sinus rhythm. No significant difference between CAF and PAF was found. The expression of ACE was three-fold increased in the patients with CAF compared to those with sinus rhythm. Patients with AF showed an increased expression of ERK1/ERK2 in atrial interstitial cells and marked atrial fibrosis. An ACE-dependent increase in the amounts of activated ERK1/ERK2 in atrial interstitial cells may be one of molecular mechanisms for the development of atrial fibrosis in the patients with AF. These findings may have important impact on the treatment of AF.

  11. Angiotensin-converting enzyme inhibitory activity of milk fermented by wild and industrial Lactococcus lactis strains.

    Rodríguez-Figueroa, J C; Reyes-Díaz, R; González-Córdova, A F; Troncoso-Rojas, R; Vargas-Arispuro, I; Vallejo-Cordoba, B

    2010-11-01

    Angiotensin I-converting enzyme inhibitory (ACEI) activity was evaluated and compared in milk fermented by wild and commercial starter culture Lactococcus lactis strains after 48 h of incubation. The highest ACEI activities were found in WSE from milk inoculated with wild L. lactis strains isolated from artisanal dairy products and commercial starter cultures. On the other hand, the lowest ACEI activities were found in WSE from milk inoculated with wild strains isolated from vegetables. Moreover, the IC(50) values (concentration that inhibits 50% activity) of WSE from artisanal dairy products were the lowest, indicating that these fractions were the most effective in inhibiting 50% of ACE activity. In fact, a strain isolated from artisanal cheese presented the lowest IC(50) (13 μg/mL). Thus, it appears that wild L. lactis strains isolated from artisanal dairy products and commercial starter cultures showed good potential for the production of fermented dairy products with ACEI properties. PMID:20965317

  12. Peptides Derived from Rhopilema esculentum Hydrolysate Exhibit Angiotensin Converting Enzyme (ACE Inhibitory and Antioxidant Abilities

    Jun Li

    2014-09-01

    Full Text Available Jellyfish (Rhopilema esculentum was hydrolyzed using alcalase, and two peptides with angiotensin-I-converting enzyme (ACE inhibitory and antioxidant activities were purified by ultrafiltration and consecutive chromatographic methods. The amino acid sequences of the two peptides were identified as VKP (342 Da and VKCFR (651 Da by electrospray ionization tandem mass spectrometry. The IC50 values of ACE inhibitory activities of the two peptides were 1.3 μM and 34.5 μM, respectively. Molecular docking results suggested that VKP and VKCFR bind to ACE through coordinating with the active site Zn(II atom. Free radical scavenging activity and protection against hydrogen peroxide (H2O2-induced rat cerebral microvascular endothelial cell (RCMEC injury were used to evaluate the antioxidant activities of the two peptides. As the results clearly showed that the peptides increased the superoxide dismutase (SOD, catalase (CAT and glutathione peroxidase (GSH-px activities in RCMEC cells, it is proposed that the R. esculentum peptides exert significant antioxidant effects.

  13. Angiotensin Converting Enzyme Gene Polymorphism in Egyptian Patients with Systemic Lupus Erythematosus

    El-Shafeey M.M., El-Shayeb M., Othman E. and Elfawy N

    2005-12-01

    Full Text Available Systemic lupus erythematosus (SLE shows various clinical manifestations with various immunological abnormalities. The development of lupus nephritis and vasculitis is common in patients with SLE. As angiotensin I-converting enzyme (ACE has been reported to be associated with various immunological phenomena, we investigated the correlation between insertion(I / deletion(D polymorphism of the ACE gene and SLE. Fifty Egyptian patients with SLE and thirty healthy control persons were involved in this study. ACE gene was detected by the polymerase chain reaction (PCR. In SLE patients, there is a significant difference when comparing DD and II genotypes (P<0.05,being higher in the DD genotype. And a highly significant difference when comparing ID and II genotypes (P=0.001, being much higher in ID genotype than II genotype. According to vasculitis, there is a significant relationship between vasculitis and patients genotypes when comparing ID genotype with both II and DD genotypes (P<0.05, being highest in ID genotype. There is a significant relationship found when comparing ID genotype with both II and DD genotypes, being highest in ID genotype in patients with score 21. These results suggest that the ACE genotype could be associated with SLE.

  14. A randomized comparative trial of first-dose response to Angiotensin- Converting Enzyme Perindopril and Captopril in Indonesian heart failure patients

    Lukman H. Makmun

    2002-03-01

    Full Text Available Several large placebo-controlled trials have confirmed that angiotensin converting enzyme (ACE inhibitors significantly reduce mortality aid morbidity in all functional grades of congestive heart failure (CHF, nevertheless only a proportion of patients who may benefit from treatment are priscribed an ACE inhibitor. One of the perceived difficulties is the occurrence of first-dose hypotension in susceptible patients. A double-blind, randomised, single-dose therapy, parallel-group study was conducted with the aim to compare the first-dose responses to low dose ACE inhibitors captopril and perindopril in patients with stable chronic heart failure. Seventy patients (New York Heart Association class I-IV were included. Blood pressure was recorded every 15 minutes 2 hours before starting treatment. The mean of these readings was taken as the baseline blood pressure. Patients were randomised to receive a single-dose of captopril 6.25 mg or perindopril 2 mg. After taking the drug, blood pressure was monitored every 15 minutes for 2 hours, every 30 minutes during 5 hours then hourly after 2 hours. The maximum mean arterial pressure fall from baseline of perindopril was 0.85 mmHg compared to captopril 4.60 mmHg. The maximum mean systolic fall from baseline of perindopril was 3 '31 'mmHg compared to captopril 6.76 mmHg while the maximum mean diastolic fall from baseline of perindopril was 1.08 mmHg compared to captopril 2.63 mmHg. The hypotensive effect of the captopril group started soon after dosing and reached its maximum after 1 to 2 hours while perindopril showed slight reduction of systolic after 1 hour and slight reduction of diastolic after 4 hours. Compared to captopril, perindopril seemed to be less likely to cause first-dose hypotension in patients with heart failure. (Med J Indones 2002; 11: 19-23Keywords: first dose hypotension, perindopril, captopril, chronic heart failure

  15. Advances in effects of angiotensin converting enzyme on lung injury%血管紧张素转换酶在肺损伤中作用的研究进展

    许晓东; 徐桂萍

    2013-01-01

    Background Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a kind of inflammatory syndrome.Recent research showed that angiotensin converting enzyme (ACE) plays an important role in the development of ALI.Objective Study on renin angiotensin system (RAS),especially the role of ACE in lung injury is growing,it is necessary to understand the current research and future trends.Content The focus of this review is to summarize the relevant studies about ACE in lung injury.Trend The application of angiotensin converting enzyme inhibitor (ACEI) and angiotensin Ⅱ (AT Ⅱ) receptor blockers in various lung injury has made positive achievements,which make people understand the role of RAS in lung injury deeply.%背景 急性肺损伤(acute lung injury,ALI)/急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)是一种炎性综合征,近年研究发现血管紧张素转换酶(angiotensin converting enzyme,ACE)在其发生发展过程中起着重要作用.目的 人们对于肾素血管紧张素系统(renin angiotensin system,RAS),特别是ACE在肺损伤中的作用研究日趋深入,有必要了解其研究现状和未来趋势. 内容 重点就近几年来国内外对ACE在各种原因导致的肺损伤中作用的研究作一综述. 趋向 血管紧张素转换酶抑制剂(angiotensin converting enzyme inhibitom,ACEI)和血管紧张素Ⅱ(angiotensinⅡ,ATⅡ)受体阻断剂在各种肺损伤中的应用已取得肯定成果,使人们对RAS和其在肺损伤中作用的认识不断加深.

  16. Standardization of a fluorimetric assay for the determination of tissue angiotensin-converting enzyme activity in rats

    E.M. Oliveira

    2000-07-01

    Full Text Available The tripeptide Hip-His-Leu was used to standardize a fluorimetric method to measure tissue angiotensin-converting enzyme (ACE activity in rats. The fluorescence of the o-phthaldialdehyde-His-Leu adduct was compared in the presence and absence of the homogenate (25 µl to determine whether the homogenate from different tissues interfered with the fluorimetric determination of the His-Leu product. Only homogenates from lung and renal medulla and cortex showed significantly altered fluorescence intensity. To overcome this problem, the homogenate from these tissues were diluted 10 times with assay buffer. The specificity of the assay was demonstrated by the inhibition of ACE activity with 3 µM enalaprilat (MK-422. There was a linear relationship between product formation and incubation time for up to 90 min for homogenates of renal cortex and medulla and liver, for up to 60 min for ventricles and adrenals and for up to 30 min for the aorta, lung and atrium homogenates. In addition, there was a linear relationship between product formation and the amount of protein in the homogenates within the following range: lung, 30-600 µg; renal cortex and medulla, 40-400 µg; atrium and ventricles, 20-200 µg; adrenal, 20-100 µg; aorta, 5-100 µg; liver, 5-25 µg. No peptidase activity against the His-Leu product (31 nmol, assayed in borate buffer (BB, was detected in the different homogenates except the liver homogenate, which was inhibited by 0.1 mM r-chloromercuribenzoic acid. ACE activity in BB was higher than in phosphate buffer (PB due, at least in part, to a greater hydrolysis of the His-Leu product in PB. ACE activity of lung increased 20% when BB plus Triton was used. Enzyme activity was stable when the homogenates were stored at -20o or -70oC for at least 30 days. These results indicate a condition whereby ACE activity can be easily and efficiently assayed in rat tissue samples homogenized in BB using a fluorimetric method with Hip-His-Leu as a

  17. Effect of angiotensin-converting enzyme inhibitor, captoprol on proliferation, differentiation and migration of human epidermal stem cells%血管紧张素转化酶抑制剂对表皮干细胞增殖、分化、迁移的影响

    廖选; 肖静; 刘宏伟; 程飚; 肖丽玲; 徐媛; 李升红

    2013-01-01

    目的 观察血管紧张素转化酶(ACE)抑制剂卡托普利对表皮干细胞(ESCs)增殖、迁移、分化的影响,探讨ACE在维持ESCs生物学功能中的作用.方法 利用差速贴壁法获得10例儿童的ESCs,进行离体培养,检测ACE在ESCs的表达.用XTT法检测不同浓度(1 ×l0-5、1×10-6、l×10-7、1×10-8mol/L) ACEI卡托普利对ESCs增殖的影响;体外创伤模型观察1×10-6mol/L的卡托普利对ESCs 6、12、18、24h各时间段的迁移能力;流式细胞仪检测K10的表达观察1×10-6mol/L的卡托普利对ESCs分化的影响.结果 培养的细胞经β1-整合素和K19免疫荧光双重标记染色,83.55%细胞为双标记阳性细胞,即ESCs.免疫荧光染色和逆转录-聚合酶链反应(RT-PCR)结果显示ESCs表达ACE.流式细胞仪定量检测培养的细胞ACE阳性率为74.2%.1×10-6mol/L的卡托普利可明显抑制ESCs的增殖(P<0.05),且在第5天达到峰值.1×10-6 mol/L的卡托普利可明显抑制细胞的迁移能力(P<0.05)和克隆能力(P<0.05).流式细胞仪检测结果表明,l×10-6 mol/L的卡托普利并不影响K10的表达(P>0.05).结论 ACE通过影响ESCs的增殖,迁移从而影响皮肤的损伤修复和自我更新.%Objective To observe the effect of angiotensin-converting enzyme (ACE) inhibitor,captoprol on the proliferation,differentiation and migration of human epidermal stem cells (ESCs),and explore the role of ACE in maintaining ESCs biological function.Methods Human ESCs were isolated by differential adhesion method from human skin and cultured in vitro,and the expression of ACE,β1-integrin K19 and K10 in human ESCs was examined by using immunostaining and flow cytometry.XTT cell proliferation assay was used to detect the impact of the different concentrations of ACE inhibitor,captopril on the proliferation of ESCs,and the scratch assay was done to evaluate the effect of 1 × 10-6 mol/L captopril on the migration of ESCs.Flow cytometry was used to detect K10

  18. Comparative study of Mg/Al- and Zn/Al-layered double hydroxide-perindopril erbumine nanocomposites for inhibition of angiotensin-converting enzyme

    Hussein Al Ali SH

    2012-08-01

    Full Text Available Samer Hasan Hussein Al Ali,1 Mothanna Al-Qubaisi,2 Mohd Zobir Hussein,1,3 Maznah Ismail,2,4 Zulkarnain Zainal,1 Muhammad Nazrul Hakim51Department of Chemistry, Faculty of Science, 2Laboratory of Molecular Biomedicine, Institute of Bioscience, 3Advanced Materials and Nanotechnology Laboratory, Institute of Advanced Technology, 4Department of Nutrition and Health Science, 5Department of Biomedical Science, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor, MalaysiaAbstract: The intercalation of a drug active, perindopril, into Mg/Al-layered double hydroxide for the formation of a new nanocomposite, PMAE, was accomplished using a simple ion exchange technique. A relatively high loading percentage of perindopril of about 36.5% (w/w indicates that intercalation of the active took place in the Mg/Al inorganic interlayer. Intercalation was further supported by Fourier transform infrared spectroscopy, and thermal analysis shows markedly enhanced thermal stability of the active. The release of perindopril from the nanocomposite occurred in a controlled manner governed by pseudo-second order kinetics. MTT assay showed no cytotoxicity effects from either Mg/Al-layered double hydroxide or its nanocomposite, PMAE. Mg/Al-layered double hydroxide showed angiotensin-converting enzyme inhibitory activity, with 5.6% inhibition after 90 minutes of incubation. On incubation of angiotensin-converting enzyme with 0.5 µg/mL of the PMAE nanocomposite, inhibition of the enzyme increased from 56.6% to 70.6% at 30 and 90 minutes, respectively. These results are comparable with data reported in the literature for Zn/Al-perindopril.Keywords: magnesium, aluminum, layered double hydroxide, perindopril erbumine, ion exchange, angiotensin-converting enzyme, Chang cells line

  19. ROLE OF ANGIOTENSIN-CONVERTING ENZYME AND VITAMIN D RECEPTOR GENE POLYMORPHISMS IN CANCER ANOREXIA-CACHEXIA SYNDROME

    Ariele Fabris

    2012-01-01

    Full Text Available The ubiquitin-proteasome pathway is a crucial connection between aberrant immune system activation, systemic inflammation and Cancer Anorexia-Cachexia Syndrome (CACS, a syndrome that culminates in hyper-activation of the ubiquitin-proteasome pathway. Angiotensin directly up-regulates this pathway, while vitamin D down-regulates it indirectly through the insulin-like growth factor-1 pathway. We investigated the genetic predisposition towards CACS in a cancer population, examining Insertion/Deletion (I/D polymorphism of angiotensin-converting enzyme gene and FokI and BsmI polymorphisms of vitamin D receptor gene. Sixty-two cancer patients were recruited and divided into three groups: primary cachectic (C1, n = 14; dysmetabolic body weight loss ≥5% in 6 months; secondary cachectic (C2, n = 34; similar weight loss, mechanic or iatrogenic origin; and non-cachectic (NC, n = 16. C2+NC were merged in the control group. The three groups showed significant differences in average prognostic inflammatory nutritional index (C1: 26.4±23.4; C2: 5.4±5.6; NC: 0.37±0.5, C-reactive protein serum levels (C1: 6.6±2.1; C2: 2.4±2.2; NC: 1.0±2.0 mg/dL, albumin serum levels (C1: 3.1±0.6; C2: 3.5±0.4; NC 3.7±0.6 g/dL, weight loss (C1: 22±8; C2: 15±6.7; NC 5±6% and life expectancy (C1: 6.4±3.3; C2: 25±28; NC: 45±25 months. However, none of the chosen polymorphisms showed any statistically significant correlation with CACS. The complexity of the changes of the immune system in the chronic inflammation state associated with CACS is far greater than expected and further studies are required to identify genetic independent markers of progression toward CACS."

  20. Differential effects of isoproterenol on the activity of angiotensin-converting enzyme in the rat heart and aorta

    Busatto V.C.W.

    1999-01-01

    Full Text Available The excessive stimulation of beta-adrenergic receptors in the heart induces myocardial hypertrophy. There are several experimental data suggesting that this hypertrophy may also depend, at least partially, on the increase of local production of angiotensin II secondary to the activation of the cardiac renin-angiotensin system. In this study we investigated the effects of isoproterenol on the activity of angiotensin-converting enzyme (ACE in the heart and also in the aorta and plasma. Male Wistar rats weighing 250 to 305 g were treated with a dose of (±-isoproterenol (0.3 mg kg-1 day-1, N = 8 sufficient to produce cardiac hypertrophy without deleterious effects on the pumping capacity of the heart. Control rats (N = 7 were treated with vehicle (corn oil. The animals were killed one week later. ACE activity was determined in vitro in the four cardiac chambers, aorta and plasma by a fluorimetric assay. A significant hypertrophy was observed in both ventricular chambers. ACE activity in the atria remained constant after isoproterenol treatment. There was a significant increase (P<0.05 of ACE activity in the right ventricle (6.9 ± 0.9 to 8.2 ± 0.6 nmol His-Leu g-1 min-1 and in the left ventricle (6.4 ± 1.1 to 8.9 ± 0.8 nmol His-Leu g-1 min-1. In the aorta, however, ACE activity decreased (P<0.01 after isoproterenol (41 ± 3 to 27 ± 2 nmol His-Leu g-1 min-1 while it remained unchanged in the plasma. These data suggest that ACE expression in the heart can be increased by stimulation of beta-adrenoceptors. However, this effect is not observed on other local renin-angiotensin systems, such as the aorta. Our data also suggest that the increased sympathetic discharge and the elevated plasma concentration of catecholamines may contribute to the upregulation of ACE expression in the heart after myocardial infarction and heart failure.

  1. Role of circulating angiotensin converting enzyme 2 in left ventricular remodeling following myocardial infarction: a prospective controlled study.

    José T Ortiz-Pérez

    Full Text Available Angiotensin-converting enzyme 2 (ACE2 cleaves Angiotensin-II to Angiotensin-(1-7, a cardioprotective peptide. Serum soluble ACE2 (sACE2 activity is raised in chronic heart failure, suggesting a compensatory role in left ventricular dysfunction. Our aim was to study the relationship between sACE2 activity, infarct size, left ventricular systolic function and remodeling following ST-elevation myocardial infarction (STEMI. A contrast-enhanced cardiac magnetic resonance study was performed acutely in 95 patients with first STEMI and repeated at 6 months to measure LV end-diastolic volume index, ejection fraction and infarct size. Baseline sACE2 activities, measured by fluorescent enzymatic assay 24 to 48 hours and at 7 days from admission, were compared to that obtained in 22 matched controls. Patients showed higher sACE2 at baseline than controls (104.4 [87.4-134.8] vs 74.9 [62.8-87.5] RFU/µl/hr, p<0.001. At seven days, sACE2 activity significantly increased from baseline (115.5 [92.9-168.6] RFU/µl/hr, p<0.01. An inverse correlation between sACE2 activity with acute and follow-up ejection fraction was observed (r = -0.519, p<0.001; r = -0.453, p = 0.001, respectively. Additionally, sACE2 directly correlated with infarct size (r = 0.373, p<0.001. Both, infarct size (β = -0.470 [95%CI:-0.691:-0.248], p<0.001 and sACE2 at 7 days (β = -0.025 [95%CI:-0.048:-0.002], p = 0.030 were independent predictors of follow-up ejection fraction. Patients with sACE2 in the upper tertile had a 4.4 fold increase in the incidence of adverse left ventricular remodeling (95% confidence interval: 1.3 to 15.2, p = 0.027. In conclusion, serum sACE2 activity rises in relation to infarct size, left ventricular systolic dysfunction and is associated with the occurrence of left ventricular remodeling.

  2. Increasing brain angiotensin converting enzyme 2 activity decreases anxiety-like behavior in male mice by activating central Mas receptors.

    Wang, Lei; de Kloet, Annette D; Pati, Dipanwita; Hiller, Helmut; Smith, Justin A; Pioquinto, David J; Ludin, Jacob A; Oh, S Paul; Katovich, Michael J; Frazier, Charles J; Raizada, Mohan K; Krause, Eric G

    2016-06-01

    Over-activation of the brain renin-angiotensin system (RAS) has been implicated in the etiology of anxiety disorders. Angiotensin converting enzyme 2 (ACE2) inhibits RAS activity by converting angiotensin-II, the effector peptide of RAS, to angiotensin-(1-7), which activates the Mas receptor (MasR). Whether increasing brain ACE2 activity reduces anxiety by stimulating central MasR is unknown. To test the hypothesis that increasing brain ACE2 activity reduces anxiety-like behavior via central MasR stimulation, we generated male mice overexpressing ACE2 (ACE2 KI mice) and wild type littermate controls (WT). ACE2 KI mice explored the open arms of the elevated plus maze (EPM) significantly more than WT, suggesting increasing ACE2 activity is anxiolytic. Central delivery of diminazene aceturate, an ACE2 activator, to C57BL/6 mice also reduced anxiety-like behavior in the EPM, but centrally administering ACE2 KI mice A-779, a MasR antagonist, abolished their anxiolytic phenotype, suggesting that ACE2 reduces anxiety-like behavior by activating central MasR. To identify the brain circuits mediating these effects, we measured Fos, a marker of neuronal activation, subsequent to EPM exposure and found that ACE2 KI mice had decreased Fos in the bed nucleus of stria terminalis but had increased Fos in the basolateral amygdala (BLA). Within the BLA, we determined that ∼62% of GABAergic neurons contained MasR mRNA and expression of MasR mRNA was upregulated by ACE2 overexpression, suggesting that ACE2 may influence GABA neurotransmission within the BLA via MasR activation. Indeed, ACE2 overexpression was associated with increased frequency of spontaneous inhibitory postsynaptic currents (indicative of presynaptic release of GABA) onto BLA pyramidal neurons and central infusion of A-779 eliminated this effect. Collectively, these results suggest that ACE2 may reduce anxiety-like behavior by activating central MasR that facilitate GABA release onto pyramidal neurons within the

  3. [STUDIES IN VITRO INHIBITION OF THE ANGIOTENSIN-CONVERTING ENZYME-I, HYPOTENSIVE AND ANTIHYPERTENSIVE EFFECTS OF PEPTIDE FRACTIONS OF V. UNGUICULATA].

    Cú-Cañetas, Trinidad; Betancur Ancona, David; Gallegos Tintoré, Santiago; Sandoval Peraza, Mukthar; Chel Guerrero, Luis

    2015-01-01

    Inhibition of angiotensin-converting enzyme I (ACE-I) in vitro and in vivo from peptide fractions by enzymatic hydrolysis of the Vigna unguiculata protein concentrate was evaluated. Hydrolysis was done with Pepsin-Pancreatin and Flavourzima in two separate systems. The resulting hidrolysates were ultrafiltrated to obtain fractions with different molecular weight. The fractions with better inhibition Flavourzima were size > 1 kDa (> 1 kDa-F) and < 1 kDa (< 1 kDa-F), with an IC50 of 1222.84 and 1098.6 μg/ml respectively. Pepsin-Pancreatin fraction. PMID:26545668

  4. Effects of steroids and angiotensin converting enzyme inhibition on circumferential strain in boys with Duchenne muscular dystrophy: a cross-sectional and longitudinal study utilizing cardiovascular magnetic resonance

    Kinnett Kathi J

    2011-10-01

    Full Text Available Abstract Background Steroid use has prolonged ambulation in Duchenne muscular dystrophy (DMD and combined with advances in respiratory care overall management has improved such that cardiac manifestations have become the major cause of death. Unfortunately, there is no consensus for DMD-associated cardiac disease management. Our purpose was to assess effects of steroid use alone or in combination with angiotensin converting enzyme inhibitors (ACEI or angiotension receptor blocker (ARB on cardiovascular magnetic resonance (CMR derived circumferential strain (εcc. Methods We used CMR to assess effects of corticosteroids alone (Group A or in combination with ACEI or ARB (Group B on heart rate (HR, left ventricular ejection fraction (LVEF, mass (LVM, end diastolic volume (LVEDV and circumferential strain (εcc in a cohort of 171 DMD patients >5 years of age. Treatment decisions were made independently by physicians at both our institution and referral centers and not based on CMR results. Results Patients in Group A (114 studies were younger than those in Group B (92 studies(10 ± 2.4 vs. 12.4 ± 3.2 years, p cc magnitude was lower in Group B than Group A (-13.8 ± 1.9 vs. -12.8 ± 2.0, p = 0.0004, age correction using covariance analysis eliminated this effect. In a subset of patients who underwent serial CMR exams with an inter-study time of ~15 months, εcc worsened regardless of treatment group. Conclusions These results support the need for prospective clinical trials to identify more effective treatment regimens for DMD associated cardiac disease.

  5. Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: Possible involvement of angiotensin-converting enzyme-2

    Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin-angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH and its possible mechanism, rats were daily exposed to cigarette smoke for 6 months in the absence and in the presence of losartan. Elevated right ventricular systolic pressure (RVSP), thickened wall of pulmonary arteries with apparent medial hypertrophy along with increased angiotensin II (Ang II) and decreased ACE2 levels were observed in smoke-exposed-only rats. Losartan administration ameliorated pulmonary vascular remodeling, inhibited the smoke-induced RVSP and Ang II elevation and partially reversed the ACE2 decrease in rat lungs. In cultured primary pulmonary artery smooth muscle cells (PASMCs) from 3- and 6-month smoke-exposed rats, ACE2 levels were significantly lower than in those from the control rats. Moreover, PASMCs from 6-month exposed rats proliferated more rapidly than those from 3-month exposed or control rats, and cells grew even more rapidly in the presence of DX600, an ACE2 inhibitor. Consistent with the in vivo study, in vitro losartan pretreatment also inhibited cigarette smoke extract (CSE)-induced cell proliferation and ACE2 reduction in rat PASMCs. The results suggest that losartan may be therapeutically useful in the chronic smoking-induced pulmonary vascular remodeling and PAH and ACE2 may be involved as part of its mechanism. Our study might provide insight into the development of new therapeutic interventions for PAH smokers.

  6. Hypertension exacerbates predisposition to neurodegeneration and memory impairment in the presence of a neuroinflammatory stimulus: Protection by angiotensin converting enzyme inhibition.

    Goel, Ruby; Bhat, Shahnawaz Ali; Rajasekar, N; Hanif, Kashif; Nath, Chandishwar; Shukla, Rakesh

    2015-06-01

    Hypertension is a risk factor for cognitive impairment. Furthermore, neuroinflammation and neurodegeneration are intricately associated with memory impairment. Therefore, the present study aimed to explore the involvement of hypertension and angiotensin system in neurodegeneration and memory dysfunction in the presence of neuroinflammatory stimulus. Memory impairment was induced by chronic neuroinflammation that was developed by repeated intracerebroventricular (ICV) injections of lipopolysaccharide (LPS) on the 1st, 4th, 7th, and 10th day. Memory functions were evaluated by the Morris water maze (MWM) test on days 13-15, followed by biochemical and molecular studies in the cortex and hippocampus regions of rat brain. LPS at the dose of 25μg ICV caused memory impairment in spontaneously hypertensive rats (SHRs) but not in normotensive Wistar rats (NWRs). Memory deficit was obtained with 50μg of LPS (ICV) in NWRs. Control SHRs already exhibited increased angiotensin converting enzyme (ACE) activity and expression, neuroinflammation (increased TNF-α, GFAP, COX-2 and NF-kB), oxidative stress (increased iNOS, ROS and nitrite levels), TLR-4 expression and TUNEL positive cells as compared to control NWRs. Further, LPS (25μg ICV) exaggerated inflammatory response, oxidative stress and apoptosis in SHRs but similar effects were witnessed at 50μg of LPS (ICV) in NWRs. Oral administration of perindopril (ACE inhibitor), at non-antihypertensive dose (0.1mg/kg), for 15days attenuated LPS induced deleterious changes in both NWRs and SHRs. Our data suggest that susceptibility of the brain for neurodegeneration and memory impairment induced by neuroinflammation is enhanced in hypertension, and that can be protected by ACE inhibition. PMID:25869103

  7. 汉族人群中血管紧张素转换酶抑制剂所致咳嗽与血管紧张素转换酶基因及缓激肽β2受体基因多态性的关系%The Association between ACE Inhibitor (ACEI)-Induced Cough and the Polymorphism of Angiotensin Converting Enzyme (ACE) Gene and Bradykinin β2 Receptor(BDKRB2) Gene in Han Nationality

    王刚; 杨军; 唐振旺; 宁国庆; 曹燕; 万娟

    2012-01-01

    Objective: To investigate the association between angiotensin converting enzyme inhibitor (ACEI)-induced cough and the polymorphism of angiotensin converting enzyme (ACE) gene and bradykinin ($2 receptor (BDKRB2) gene in Han nationality. Methods: Polymerase chain reaction (PCR) was used to examine ACE I/D and BDKRB2 CT polymorphism in 151 ACEI-induced cough subjects and 151 no cough subjects in Han population. And UV-method was used to detect the ACE activity. Results:ACE gene distribution in the cough group: type II was 47.0%, ID genotype was 42.4%, DD genotype was 10.6%; Non-cough group were 39.7%, 47.0%, 13.3% respectively, and there was statistically significant difference between the two groups(P 0.05); The level of ACE activity in the Cough group [(28.3 ± 10.1) U / L,] was significantly lower than non-cough group [(40.2 ± 9.4) U / L,(P <0.01).]. Conclusions: For han population, ACEI-induced cough related to ACE gene polymorphism and serum ACE activity, and there was no statistically significant association between BDKRB2 C / T and cough.%目的:探讨汉族人群中血管紧张素转换酶抑制剂(ACEI)所致咳嗽与血管紧张素转换酶(ACE)基因及缓激肽β2受体(BDKRB2)基因多态性的关系.方法:应用聚合酶链反应(PCR)方法,检测汉族人群中151例由于服用ACEI引起的咳嗽患者及151例未发生咳嗽的患者的ACEI/D及BDKRB2C/T的多态性,并采用紫外法检测ACE活性.结果:发现ACE基因分布在咳嗽组中Ⅱ型为47.0%,ID型为42.4%,DD型为10.6%;无咳嗽组分别为39.7%、47.0%、13.3%,两组相比其差异具有统计学意义(P<0.01);BDKRB2基因分布在咳嗽组中CC型为21.3%,CT型为50.0%,TT型为28.7%,无咳嗽组分别为22.5%、47.7%、29.8%,两组相比其差异无统计学意义(P>0.05);咳嗽组ACE活性水平为[(28.3±10.1)U/L]明显低于无咳嗽组[(40.2± 9.4)U/L],两组相比其差异具有统计学意义(P<0.01).结论:汉族人群中ACEI所致咳嗽

  8. Association between insertion/deletion polymorphism in angiotensin-converting enzyme gene and acute lung injury/acute respiratory distress syndrome: a meta-analysis

    Matsuda Akihisa

    2012-08-01

    Full Text Available Abstract Background A previous meta-analysis reported a positive association between an insertion/deletion (I/D polymorphism in the angiotensin-converting enzyme gene (ACE and the risk of acute lung injury (ALI/acute respiratory distress syndrome (ARDS. Here, we updated this meta-analysis and additionally assessed the association of this polymorphism with ALI/ARDS mortality. Methods We searched electronic databases through October 2011 for the terms “angiotensin-converting enzyme gene”, “acute lung injury”, and “acute respiratory distress syndrome,” and reviewed all studies that reported the relationship of the I/D polymorphism in ACE with ALI/ARDS in humans. Seven studies met the inclusion criteria, comprising 532 ALI/ARDS patients, 3032 healthy controls, and 1432 patients without ALI/ARDS. We used three genetic models: the allele, dominant, and recessive models. Results The ACE I/D polymorphism was not associated with susceptibility to ALI/ARDS for any genetic model. However, the ACE I/D polymorphism was associated with the mortality risk of ALI/ARDS in Asian subjects ( Pallele Pdominant = 0.001, Precessive = 0.002. This finding remained significant after correction for multiple comparisons. Conclusions There is a possible association between the ACE I/D polymorphism genotype and the mortality risk of ALI/ARDS in Asians.

  9. 中药材中血管紧张素转化酶抑制剂的筛选及其有效成分预测%Screening of angiotensin-converting enzyme inhibitors and their efficacy prediction in traditional Chinese medicine

    吴祥贵; 邸欣; 王鑫; 刘有平

    2016-01-01

    目的 以金银花等16味中药材为研究对象,建立毛细管区带电泳法用于血管紧张素转化酶(angiotensin converting enzyme,ACE)中药抑制剂的快速筛选,并采用分子对接技术对产生抑制活性的有效成分进行预测.方法 采用毛细管区带电泳法检测酶孵育产物的质量浓度,通过与空白组比较,确定中药水提液对ACE的抑制活性.采用Autodock软件对酶抑制效果较好的中药提取液主要化学成分进行分子对接,预测产生酶抑制作用的有效成分,并采用文献报道的实测数据与预测结果进行比较,对试验的可行性进行佐证.结果 建立的测定ACE活性的毛细管区带电泳法可用于16种中药水提液对ACE抑制剂的筛选.试验结果显示所研究的中药提取液中金银花的活性最强,并且分子对接结果表明,金银花中可能有7种化学成分对ACE有抑制作用,其中4种成分的抑制活性已有文献报道.结论 将毛细管区带电泳法结合分子对接技术用于从中药成分中高通量筛选ACE抑制剂是一种有效的途径.

  10. Progress of research on angiotensin-converting enzyme 2 in%血管紧张素转化酶2和肺部疾病的研究进展

    胡晓维; 章锐锋; 应可净

    2011-01-01

    @@ 在传统肾素-血管紧张素系统(renin-angiotensin system,RAS)中,血管紧张素转化酶(angiotensin-converting enzyme, ACE)通过催化血管紧张素Ⅱ (angiotensin Ⅱ, Ang Ⅱ)产生,从而促进肺动脉高压、肺纤维化等肺部疾病发生.RAS系统抑制类药物,如血管紧张素转化酶抑制剂(ACE inhibitor, ACEI)和Ang Ⅱ受体拮抗剂(Ang Ⅱ receptor blocker, ARB)曾用于治疗此类疾病,但其疗效尚不明确.

  11. Status of Angiotensin-converting Enzyme Inhibitors (ACEI) and Progress of the Research on ACEI from Natural Sources%血管紧张素转化酶抑制剂(ACEI)现状与天然ACEI的研究进展

    刘会敏; 张聪颖; 曹雨; 孔毅; 杜迎翔

    2012-01-01

    血管紧张素转化酶(ACE)在血压调节中起着重要作用,ACE抑制剂(ACEI)可以抑制ACE的活性,从而阻碍血管紧张素Ⅱ的生成和舒缓激肽的失活,使血压下降.文中介绍了ACEI的作用机制、合成ACEI的现状、国内外天然ACEI的研究现状、活性检测方法,以期为ACEI进一步研究提供参考.%Angiotensin I converting enzyme (ACE) plays an important physiological role in the regulation of high blood pressure. Inhibition of ACE activity leads to a decrease in the concentration of angiotensin Ⅱ and inactivates catalytic function of bradykinin with a concomitant reduction of blood pressure. Therefore, inhibition of ACE is considered to be an important therapeutic approach for controlling hypertension . This review details the information on the mechanism of action of ACEI, the present situation of synthesizing ACE inhibitors and the natural ACE inhibitors as well as,activity determination. The aim of this work is to provide some references for further research on ACE inhibitors.

  12. In Vitro and In Vivo Assessment of Angiotensin-Converting Enzyme (ACE) Inhibitory Activity of Fermented Soybean Milk by Lactobacillus casei Strains.

    Bao, Zhijie; Chi, Yujie

    2016-08-01

    Angiotensin-converting enzyme (ACE) inhibitory activity of fermented soybean milk (FSM) by Lactobacillus casei strains in vitro was investigated in this study. Effects of fermented soybean milk administration by gavage on systolic blood pressure and diastolic blood pressure was also evaluated in spontaneously hypertensive rats (SHR) rats and Wistar-Kyoto (WKY) rats. Results showed that, CICC 20280 and CICC 23184 FSM showed high ACE inhibitory activity in vitro test and ACE inhibitory activity of CICC 23184 FSM was higher than CICC 20280 FSM. The bioactive substances of FSM were peptide and γ-aminobutyric acid (GABA). Their contents in CICC 20280 FSM and CICC 23184 FSM were 3.97 ± 0.67 mg/ml (peptide), 1.71 ± 0.36 mg/ml (GABA) and 5.17 ± 0.22 mg/ml (peptide), 1.57 ± 0.21 mg/ml (GABA), respectively. Moreover, CICC 20280 and CICC 23184 FSM administration by gavage could effectively lower the blood pressure of SHR to a normal level, while there was no effect on blood pressure of WKY rats. This result indicated that the bioactive substances could play an antihypertensive role when the blood pressure was not within the normal levels (high levels). PMID:27139252

  13. Short communication: Measuring the angiotensin-converting enzyme inhibitory activity of an 8-amino acid (8mer) fragment of the C12 antihypertensive peptide.

    Paul, Moushumi; Phillips, John G; Renye, John A

    2016-05-01

    An 8-AA (8mer) fragment (PFPEVFGK) of a known antihypertensive peptide derived from bovine αS1-casein (C12 antihypertensive peptide) was synthesized by microwave-assisted solid-phase peptide synthesis and purified by reverse phase HPLC. Its ability to inhibit angiotensin-converting enzyme (ACE) was assessed and compared with that of the parent 12mer peptide (FFVAPFPEVFGK) to determine the effect of truncating the sequence on overall hypotensive activity. The activity of the truncated 8mer peptide was found to be almost 1.5 times less active than that of the 12mer, with ACE-inhibiting IC50 (half-maximal inhibitory concentration) values of 108 and 69μM, for the 8mer and 12mer, respectively. Although the 8mer peptide is less active than the original 12mer peptide, its overall activity is comparable to activities reported for other small proteins that elicit physiological responses within humans. These results suggest that microbial degradation of the 12mer peptide would not result in a complete loss of antihypertensive activity if used to supplement fermented foods and that the stable 8mer peptide could have potential as a blood pressure-lowering agent for use in functional foods. PMID:26971162

  14. Comparison of gallium-67 scanning, bronchoalveolar lavage, and serum angiotensin-converting enzyme levels in pulmonary sarcoidosis. Predicting response to therapy

    Patients with active pulmonary sarcoidosis underwent bronchoalveolar lavage, gallium scan, and serum angiotensin-converting enzyme (ACE) level determination prior to treatment with corticosteroids. Pulmonary function was tested before and after therapy. Increase in vital capacity after treatment ranged from 40 to 1,030 ml; 12 of the 16 patients studied had an increase of more than 200 ml. There was a close correlation between the percentage uptake of gallium scan and the increase of the vital capacity after therapy (r . 0.95, p less than 0.01). There was no relationship between the percentage of lymphocytes obtained on lavage and the changes in vital capacity with therapy (r . 0.05). There was a positive correlation between the changes in vital capacity and the ratio of T4(+):T8(+)lymphocytes (r . 0.62, p less than 0.05) and number of T4 (+) lymphocytes (r . 0.92, p less than 0.01) in the bronchoalveolar fluid. There was a low correlation between the pretreatment ACE level and the change in vital capacity (r . 0.368, p greater than 0.05)

  15. Association between angiotensin converting enzyme gene insertion/deletion polymorphism and renal scar risk in children vesicoureteral reflex: a reappraise meta-analysis

    Ai, Jin-Wei; Zeng, Xian-Tao; Liu, Ying; Fu, Yu; Liu, Tong-Zu; Pei, Bin

    2016-01-01

    Vesicoureteral reflex(VUR) is a common disease in children. Some studies indicated that the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism associated with the renal scar in VUR, but not all researchers agreed with it. To clarify the effect of ACE I/D polymorphism on renal scar risk in children with VUR, we performed the present meta-analysis. PubMed, CNKI, CBM, and Embase databases were searched for studies that examined the relationship between ACE I/D polymorphism and renal scar risk in children with VUR. The Stata 12.0 software was used for statistical analyses. 11 case-control studies with 1,032 VUR patients were analyzed. The results showed that the DD genotype and D allele were associated with renal scar risk in overall VUR patients, DD vs. DI + II: OR = 1.61, 95% CI = 1.04–2.49, P = 0.03; DD vs. II: OR = 1.78, 95% CI = 1.20–2.65, P < 0.01; D vs. I: OR = 1.38, 95% CI = 1.02–1.86, P = 0.04. Similar results were revealed in Turks, but not in Caucasians and Asians. Our meta-analysis indicated that the ACE DD genotype may increase the risk of renal scar in children with VUR. PMID:27506878

  16. Absence of association between angiotensin converting enzyme polymorphism and development of adult respiratory distress syndrome in patients with severe acute respiratory syndrome: a case control study

    Chiu Rossa WK

    2005-04-01

    Full Text Available Abstract Background It has been postulated that genetic predisposition may influence the susceptibility to SARS-coronavirus infection and disease outcomes. A recent study has suggested that the deletion allele (D allele of the angiotensin converting enzyme (ACE gene is associated with hypoxemia in SARS patients. Moreover, the ACE D allele has been shown to be more prevalent in patients suffering from adult respiratory distress syndrome (ARDS in a previous study. Thus, we have investigated the association between ACE insertion/deletion (I/D polymorphism and the progression to ARDS or requirement of intensive care in SARS patients. Method One hundred and forty genetically unrelated Chinese SARS patients and 326 healthy volunteers were recruited. The ACE I/D genotypes were determined by polymerase chain reaction and agarose gel electrophoresis. Results There is no significant difference in the genotypic distributions and the allelic frequencies of the ACE I/D polymorphism between the SARS patients and the healthy control subjects. Moreover, there is also no evidence that ACE I/D polymorphism is associated with the progression to ARDS or the requirement of intensive care in the SARS patients. In multivariate logistic analysis, age is the only factor associated with the development of ARDS while age and male sex are independent factors associated with the requirement of intensive care. Conclusion The ACE I/D polymorphism is not directly related to increased susceptibility to SARS-coronavirus infection and is not associated with poor outcomes after SARS-coronavirus infection.

  17. 血管紧张素转换酶抑制剂治疗高血压病人的疗效与血管紧张素转换酶基因多态性的关系%Relationship Between ACE I/D Gene Polymorphism and the Curative Effects of Angiotensin-converting Enzyme Inhibitor in Hypertensive Individuals

    李锡明; 高春江

    2001-01-01

    目的探讨具不同血管紧张素转换酶基因插入/缺矢基因型(Angiotension-converting enzyme gene I/D genotype, ACE I/D genotype)的高血压病人对血管紧张素转换酶抑制剂(Angiotension-converting enzyme inhibitor, ACEI)治疗的反应性.方法根据ACE Ⅰ/D 基因多态性,将高血压病人分为II 组(20例),ID 组(20例),及DD 组(18例),共58例.使用西拉普利2.5mg Q.D,两周后无效增至5mg Q.D共4周,观察降压疗效.结果 II组显效2例,有效12例,总有效率70%;ID组显效8例,有效8例,总有效率80%;DD组显效13例,有效4例,总有效率94%.ACEI 对DD组疗效最好(P<0.01),降压幅度最大,ID组次之,II组较差.结论 ACE I/D 基因多态性可做为高血压病人选用ACEI 时的参考指标之一.

  18. Effect of a cheese rich in angiotensin-converting enzyme-inhibiting peptides (Gamalost®) and a Gouda-type cheese on blood pressure: results of a randomised trial

    Nilsen, Rita; Pripp, Are H; Arne T. Høstmark; Haug, Anna; Skeie, Siv

    2016-01-01

    Background: High blood pressure (BP) is the leading risk factor for global disease burden, contributing to 7% of global disability adjusted life years. Angiotensin converting enzyme (ACE)-inhibiting bioactive peptides have the potential to reduce BP in humans. These peptides have been identified in many dairy products and have been associated with significant reductions in BP.Objective: The objective of this trial was to examine whether a cheese rich in ACE-inhibiting peptides (Gamalost®), or...

  19. 苹果多酚提取物对血管紧张素转化酶活性的抑制%Inhibition of Angiotensin Converting Enzyme Activity by Apple Polyphenols

    王艺璇; 王世平; 马丽艳

    2012-01-01

    In order to research the effect of apple polyphenols of different variety and maturity on angiotensin converting enzyme activity, HPLC method was established for the analysis of ACE inhibitory activity by apple polyphenols. Effect of variety ('Fuji' and 'Rails') and maturity on the inhibition of ACE activity was studied in this research. The results showed that, when the concentration of apple polyphenols were at the range of 1-250 μg/mL, the inhibition of ACE activity by four groups of unripe 'Fuji', ripe 'Fuji', unripe 'Rails', ripe 'Rails' were more and more stronger. And IG50 value of unripe 'Fuji' apple polyphenols and ripe 'Rails' apple polyphenols were 16.9, 80.8 μg/mL, respectively. We could get the conclusion that unripe apple polyphenols had the best effect on the inhibition of ACE activity, and could be used as nature sources of ACE inhibitors.%为研究不同品种、成熟度的苹果多酚对血管紧张素转化酶(angiotensin converting enzyme,ACE)活性的影响,确立高效液相色谱法(HPLC)测定苹果多酚对血管紧张素转化酶(ACE)活性抑制的检测方法.选取‘富士’、‘国光’2个品种、2个成熟度的苹果多酚提取物作为实验材料,研究其对ACE活性的抑制.实验结果表明,多酚浓度在1~250 μg/mL范围时,未成熟‘富士’、成熟‘富士’、未成熟‘国光’、成熟‘国光’的苹果多酚对ACE活性的抑制逐渐增强,其中未成熟‘富士’多酚提取物的半抑制率浓度IC50值最低,成熟‘国光’的IC50值最高,分别为16.9、80.8 μg/mL.由以上结果得出,未成熟‘富士’的苹果多酚对ACE活性的抑制作用最强,可以作为天然优良的ACE活性抑制剂.

  20. Preparation of bioactive peptides with high angiotensin converting enzyme inhibitory activity from winged bean [Psophocarpus tetragonolobus (L.) DC.] seed

    Wan Mohtar, Wan Abd Al-Qadr Imad; Hamid, Azizah Abdul; Abd-Aziz, Suraini; Muhamad, Sharifah Kharidah Syed; Saari, Nazamid

    2013-01-01

    Winged bean [Psophocarpus tetragonolobus (L.) DC.] seed is a potential underexploited source of vegetable protein due to its high protein content. In the present work, undefatted and defatted winged bean seed hydrolysates, designated as UWBSH and DWBSH, respectively were produced separately by four proteolytic enzymes namely Flavourzyme, Alcalase, Bromelain, and Papain using pH-stat method in a batch reactor. Enzymatic hydrolysis was carried out over a period of 0.5 to 5 h. UWBSH and DWBSH pr...

  1. 血管紧张素转换酶抑制剂和血管紧张素受体拮抗剂对扩张型心肌病内皮功能的影响%Effects of Angiotensin Converting Enzyme Inhibitor or Angiotensin Receptor Blocker to Endothelium Function in Idiopathic Dilated Cardiomyopathy

    陈嫦娥

    2014-01-01

    目的:探讨血管紧张素转换酶抑制剂(angiotension converting enzyme inhibitor,ACEI)达爽和血管紧张素受体拮抗剂(angiotension receptor blocker,ARB)安博维对扩张型心肌病患者内皮功能的影响。方法:采用超声肱动脉内径测量法,对20例正常人和24例扩张型心肌病患者服用达爽或安博维治疗前后肱动脉内径在反应性充血后和含服硝酸甘油后的百分变化率进行比较,分析ACE-I和ARB对扩张型心肌病内皮功能的影响。结果:治疗前扩张型心肌病患者肱动脉内径在反应性充血前后变化较小,但与对照组比较差异均有统计学意义(P0.05)。结论:ACE-I和ARB均可改善扩张型心肌病的内皮功能,两者在治疗效果上差异不明显。%Objective:To evaluate the effects of angiotension converting enzyme inhibitor(ACEI) imidapril or angiotension receptor blocker (ARB)irbesartan on the endothelial function in patients with idiopathic dilated cardiomyopathy by transthoracic echocardiography.Method:Twenty-four patients with idiopathic dilated cardiomyopathy and 20 healthy subjects were included in this study. Brachial artery endothelium dependent dilation function [flow-mediated dilation(FMD)] and nitroglycerin-induced percent changes in the brachial artery diameter were measured by two-dimensional ultrasound before and after the treatment of imidapril or irbesartan and the effect of ACE-I and ARB on endothelial function in dicated cordiomyopathy were analyzed. Result:The treatment of dilated cardiomyopathy patients in the brachial artery diameter had smaller changes before and after the reactive hyperemia,but with the control group had significant difference(P0.05).Conclusion:ACE-I and ARB can improve the endothelial function in patients with dilated cardiomyopathy,the treatment effect is not obvious difference.

  2. Fast high-throughput screening of angiotensin-converting enzyme insertion/deletion polymorphism by variable programmed electric field strength-based microchip electrophoresis.

    Sun, Yucheng; Kim, Su-Kang; Zhang, Peng; Woo, Nain; Kang, Seong Ho

    2016-08-15

    An insertion (I)/deletion (D) polymorphism in angiotensin-converting enzyme (ACE) has been associated with susceptibility to various diseases in numerous studies. Traditionally, slab gel electrophoresis (SGE) after polymerase chain reaction (PCR) has been used to genotype this ACE I/D polymorphism. In this study, single- and multi-channel microchip electrophoresis (ME) methods based on variable programmed electric field strength (PEFS) (i.e., low constant, high constant, (+)/(-) staircase, and random electric field strengths) were developed for fast high-throughput screening of this specific polymorphism. The optimum PEFS conditions were set as 470V/cm for 0-9s, 129V/cm for 9-13s, 470V/cm for 13-13.9s, 294V/cm for 13.9-16s, and 470V/cm for 16-20s for single-channel ME, and 615V/cm for 0-22.5s, 231V/cm for 22.5-28.5s, and 615V/cm for 28.5-40s for multi-channel ME, respectively. In the multi-channel PEFS-ME, target ACE I/D polymorphism DNA fragments (D=190bp and I=490bp) were identified within 25s without loss of resolving power, which was ∼300 times faster than conventional SGE. In addition, PCR products of the ACE gene from human blood samples were detected after only 10 cycles by multi-channel PEFS-ME, but not by SGE. This parallel detection multichannel-based PEFS-ME method offers a powerful tool for fast high-throughput ACE I/D polymorphism screening with high sensitivity. PMID:27322633

  3. Impact of non-starter lactobacilli on release of peptides with angiotensin-converting enzyme inhibitory and antioxidant activities during bovine milk fermentation.

    Solieri, Lisa; Rutella, Giuseppina Sefora; Tagliazucchi, Davide

    2015-10-01

    This study aimed at evaluating non-starter lactobacilli (NSLAB) isolated from cheeses for their proteolytic activity and capability to produce fermented milk enriched in angiotensin-converting enzyme (ACE)-inhibitory and antioxidant peptides. Preliminarily, 34 NSLAB from Parmigiano Reggiano (PR) and 5 from Pecorino Siciliano cheeses were screened based on their capacity to hydrolyze milk proteins. Two NSLAB strains from PR, Lactobacillus casei PRA205 and Lactobacillus rhamnosus PRA331, showed the most proteolytic phenotype and were positively selected to inoculate sterile cow milk. The fermentation process was monitored by measuring viable cell population, kinetic of acidification, consumption of lactose, and synthesis of lactic acid. Milk fermented with Lb. casei PRA205 exhibited higher radical scavenging (1184.83 ± 40.28 mmol/L trolox equivalents) and stronger ACE-inhibitory (IC50 = 54.57 μg/mL) activities than milk fermented with Lb. rhamnosus PRA331 (939.22 ± 82.68 mmol/L trolox equivalents; IC50 = 212.38 μg/mL). Similarly, Lb. casei PRA205 showed the highest production of ACE-inhibitory peptides Val-Pro-Pro and Ile-Pro-Pro, which reached concentrations of 32.88 and 7.52 mg/L after 87 and 96 h of milk fermentation, respectively. This evidence supports Lb. casei PRA205, previously demonstrated to possess characteristics compatible with probiotic properties, as a promising functional culture able to promote health benefits in dairy foods. PMID:26187835

  4. Analysis of the apo E/apo C-I, angiotensin converting enzyme and methylenetetrahydrofolate reductase genes as candidates affecting human longevity.

    Galinsky, D; Tysoe, C; Brayne, C E; Easton, D F; Huppert, F A; Dening, T R; Paykel, E S; Rubinsztein, D C

    1997-03-21

    Genetic factors are likely to affect human survival, since twin studies have shown greater concordance for age of death in monozygotic compared to dizygotic twins. Coronary artery disease is an important contributor to premature mortality in the UK. Accordingly, we have chosen genes associated with cardiovascular risk, apo E/apo C-I, angiotensin converting enzyme (ACE) and methylenetetrahydrofolate reductase (MTHFR), as candidates which may affect longevity/survival into old age. An association study was performed by comparing allele and genotype frequencies at polymorphic loci associated with these genes in 182 women and 100 men aged 84 years and older with 100 boys and 100 girls younger than 17 years. MTHFR allele and genotype frequencies were similar in the elderly and young populations. Apo C-I allele and genotype frequencies were significantly different in the elderly women compared to the younger sample (P Hardy-Weinberg equilibrium and compared to observed genotypes in elderly men and women. In contrast to previous studies, apo E2 was not overrepresented in the elderly men or women. Thus, the proposition that apo E2, E3 and E4 protein isoforms are themselves functionally associated with increasing risks for early death, may be too simplistic. The I/I ACE was depleted in the elderly males but not the elderly females. Furthermore, significant differences were observed between ACE genotypes in elderly men and elderly women. These data suggest that the penetrance of loci which influence survival may vary according to sex. The depletion of the ACE I/I genotype in elderly men is generally consistent with a previous study which found decreased frequencies of the I allele in French centenarians compared to younger controls. However, these results are apparently paradoxical, since others have suggested that the I allele is associated with increased cardiovascular risk. Clarification of the overall effect of a genotype on survival will be vital if therapies are to be

  5. Early detection of oxygen-induced lung injury in conscious rabbits. Reduced in vivo activity of angiotensin converting enzyme and removal of 5-hydroxytryptamine

    Changes in lung endothelial metabolic function, determined in vitro, have been proposed as sensitive indexes of hyperoxic lung damage. However, it is unclear whether these changes are also seen in vivo. We studied the possibility, using conscious rabbits in which jugular and carotid catheters had previously been placed under halothane anesthesia. Approximately 24 h later, test animals were exposed to normobaric hyperoxia (96 +/- 2%), while a second group was maintained in room air. Multiple indicator dilution methods were used to study (1) metabolism of 3H-benzoyl-phe-ala-pro (BPAP), a synthetic substrate for angiotensin converting enzyme (ACE), and (2) removal of 14C-5-hydroxytryptamine (5-HT) during a single transpulmonary passage in conscious animals. Lungs of air-exposed animals hydrolyzed 81 +/- 2% of injected BPAP (0.1 to 0.15 nmoles) during a single passage. Percent metabolism was unaltered during the next 72 h. However, in test animals, ACE activity, as reflected by BPAP metabolism, was significantly reduced after 16 h of exposure to oxygen (77 +/- 2%, p less than 0.01) and continued to decrease to a nadir of 66 +/- 3% at 40 h. Single-pass lung uptake of 14C-5-HT (77 +/- 2%) was unchanged throughout the 72-h period in air-exposed rabbits. In test animals, 14C-5-HT removal decreased to 65 +/- 4% (p less than 0.01) after 24 h of oxygen exposure; 5-HT removal remained depressed compared with the 0 h control determination for the oxygen group at all subsequent measurement intervals. Light and electron microscopy of lungs from oxygen-exposed rabbits demonstrating reduced 5-HT removal and ACE activity at 24 h revealed normal endothelial and type I cell morphologic features

  6. Angiotensin-converting enzyme inhibition prevents myocardial infarction-induced increase in renal cortical cGMP and cAMP phosphodiesterase activities.

    Clauss, François; Charloux, Anne; Piquard, François; Doutreleau, Stéphane; Talha, Samy; Zoll, Joffrey; Lugnier, Claire; Geny, Bernard

    2015-08-01

    We investigated whether myocardial infarction (MI) enhances renal phosphodiesterases (PDE) activities, investigating particularly the relative contribution of PDE1-5 isozymes in total PDE activity involved in both cGMP and cAMP pathways, and whether angiotensin-converting enzyme inhibition (ACEi) decreases such renal PDE hyperactivities. We also investigated whether ACEi might thereby improve atrial natriuretic peptide (ANP) efficiency. We studied renal cortical PDE1-5 isozyme activities in sham (SH)-operated, MI rats and in MI rats treated with perindopril (ACEi) 1 month after coronary artery ligation. Circulating atrial natriuretic peptide (ANP), its second intracellular messenger cyclic guanosine monophosphate (cGMP) and cGMP/ANP ratio were also determined. Cortical cGMP-PDE2 (80.3 vs. 65.1 pmol/min/mg) and cGMP-PDE1 (50.7 vs. 30.1 pmol/min/mg), and cAMP-PDE2 (161 vs. 104.1 pmol/min/mg) and cAMP-PDE4 (307.5 vs. 197.2 pmol/min/mg) activities were higher in MI than in SH rats. Despite increased ANP plasma level, ANP efficiency tended to be decreased in MI compared to SH rats. Perindopril restored PDE activities and tended to improve ANP efficiency in MI rats. One month after coronary ligation, perindopril treatment of MI rats prevents the increase in renal cortical PDE activities. This may contribute to increase renal ANP efficiency in MI rats. PMID:25939307

  7. Controlled release and angiotensin-converting enzyme inhibition properties of an antihypertensive drug based on a perindopril erbumine-layered double hydroxide nanocomposite

    Hussein Al Ali SH

    2012-04-01

    Full Text Available Samer Hasan Hussein Al Ali1, Mothanna Al-Qubaisi2, Mohd Zobir Hussein1,3, Maznah Ismail2,4, Zulkarnain Zainal1, Muhammad Nazrul Hakim51Department of Chemistry, Faculty of Science, 2Laboratory of Molecular Biomedicine, Institute of Bioscience, 3Advanced Materials and Nanotechnology Laboratory, Institute of Advanced Technology, 4Department of Nutrition and Dietetics, Faculty of Medicine and Health Science, 5Department of Biomedical Science, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Serdang, Selangor, MalaysiaBackground: The intercalation of perindopril erbumine into Zn/Al-NO3-layered double hydroxide resulted in the formation of a host-guest type of material. By virtue of the ion-exchange properties of layered double hydroxide, perindopril erbumine was released in a sustained manner. Therefore, this intercalated material can be used as a controlled-release formulation.Results: Perindopril was intercalated into the interlayers and formed a well ordered, layered organic-inorganic nanocomposite. The basal spacing of the products was expanded to 21.7 Å and 19.9 Å by the ion-exchange and coprecipitation methods, respectively, in a bilayer and a monolayer arrangement, respectively. The release of perindopril from the nanocomposite synthesized by the coprecipitation method was slower than that of its counterpart synthesized by the ion-exchange method. The rate of release was governed by pseudo-second order kinetics. An in vitro antihypertensive assay showed that the intercalation process results in effectiveness similar to that of the antihypertensive properties of perindopril.Conclusion: Intercalated perindopril showed better thermal stability than its free counterpart. The resulting material showed sustained-release properties and can therefore be used as a controlled-release formulation.Keywords: perindopril erbumine, layered double hydroxides, ion-exchange, coprecipitation, sustained release, angiotensin-converting enzyme

  8. Effects of curcumin and captopril on the functions of kidney and nerve in streptozotocin-induced diabetic rats: role of angiotensin converting enzyme 1.

    Abd Allah, Eman S H; Gomaa, Asmaa M S

    2015-10-01

    Oxidative stress and inflammation are involved in the development and progression of diabetes and its complications. The renin-angiotensin system also plays an important role in the pathogenesis of diabetes and its complications. We hypothesized that curcumin and captopril would restore the kidney and nerve functions of diabetic rats through their angiotensin converting enzyme 1 (ACE1) inhibiting activity as well as their antioxidant and anti-inflammatory effects. Diabetes was induced by a single intraperitoneal injection of streptozotocin (100 mg·kg(-1) body weight). One week after induction of diabetes, rats were treated with 100 mg·kg(-1)·day(-1) curcumin or 50 mg·kg(-1)·day(-1) captopril orally for 6 weeks. Compared with diabetic control rats, curcumin- or captopril-treated diabetic rats had significantly improved blood glucose, lipid profile, kidney/body weight ratio, serum creatinine, blood urea nitrogen (BUN), and pain thresholds assessed by Von Frey filaments, hot plate test, and tail-flick test. Diabetic control rats showed increased levels of total peroxide, renal and neural tumor necrosis factor-α and interleukin-10, and renal ACE1 compared with nondiabetic rats. Although treatment with either curcumin or captopril restored the altered variables, captopril was more effective in reducing these variables. ACE1 was positively correlated with BUN and creatinine and negatively correlated with paw withdrawal threshold, hot plate reaction time, and tail-flick latency, suggesting a possible causal relationship. We conclude that curcumin and captopril protect against diabetic nephropathy and neuropathy by inhibiting ACE1 as well as oxidation and inflammation. These findings suggest that curcumin and captopril may have a role in the treatment of diabetic nephropathy and neuropathy. PMID:26398443

  9. Activation of angiotensin-converting enzyme 2 (ACE2) attenuates allergic airway inflammation in rat asthma model.

    Dhawale, Vaibhav Shrirang; Amara, Venkateswara Rao; Karpe, Pinakin Arun; Malek, Vajir; Patel, Deep; Tikoo, Kulbhushan

    2016-09-01

    Angiotensin-I converting enzyme (ACE) is positively correlated to asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS) and is highly expressed in lungs. ACE2, the counteracting enzyme of ACE, was proven to be protective in pulmonary, cardiovascular diseases. In the present study we checked the effect of ACE2 activation in animal model of asthma. Asthma was induced in male wistar rats by sensitization and challenge with ovalbumin and then treated with ACE2 activator, diminazene aceturate (DIZE) for 2weeks. 48h after last allergen challenge, animals were anesthetized, blood, BALF, femoral bone marrow lavage were collected for leucocyte count; trachea for measuring airway responsiveness to carbachol; lungs and heart were isolated for histological studies and western blotting. In our animal model, the characteristic features of asthma such as altered airway responsiveness to carbachol, eosinophilia and neutrophilia were observed. Western blotting revealed the increased pulmonary expression of ACE1, IL-1β, IL-4, NF-κB, BCL2, p-AKT, p-p38 and decreased expression of ACE2 and IκB. DIZE treatment prevented these alterations. Intraalveolar interstitial thickening, inflammatory cell infiltration, interstitial fibrosis, oxidative stress and right ventricular hypertrophy in asthma control animals were also reversed by DIZE treatment. Activation of ACE2 by DIZE conferred protection against asthma as evident from biochemical, functional, histological and molecular parameters. To the best of our knowledge, we report for the first time that activation of ACE2 by DIZE prevents asthma progression by altering AKT, p38, NF-κB and other inflammatory markers. PMID:27343405

  10. Angiotensin Converting Enzyme Gene I/D Polymorphism in Pakistani Rheumatic Heart Disease Patients and Healthy Controls

    Sadia Rehman

    2015-09-01

    Full Text Available Background: Valve scarring and collagen deposition are crucial in pathogenesis of Rheumatic Heart Disease (RHD, an autoimmune disorder of the heart. Angiotensin I-Converting Enzyme (ACE plays a major role in fibrous tissue formation. Objectives: The present research work aimed to assess the role of ACE Insertion/Deletion (I/D polymorphism in progress of RHD. Patients and Methods: DNA was pre pared from blood samples from 156 RHD patients (156 and 204 healthy ethnically-matched controls. Then, it was screened using sequence-specific Primers. Polymerase chain reaction and Agarose gel electrophoresis. The data were analyzed using Vassar stats (http://faculty.vassar.edu/lowry/VassarStats.html. Results: I allele (P = 0.024, OR = 1.42 and II genotype (P = 0.001, OR = 3.07 were significantly higher in Pakistani RHD patients compared to the healthy controls. Also, a significant difference was found between the female, but not male, patients and the controls regarding I allele and II genotype. Conclusions: The study results provided information about involvement of ACE I/D polymorphism in molecular mechanism of RHD. Thus, it can become one of the useful tools in risk assessment and help with designing strategies to combat the disease.

  11. Hydrolysates of sheep cheese whey as a source of bioactive peptides with antioxidant and angiotensin-converting enzyme inhibitory activities.

    Corrêa, Ana Paula Folmer; Daroit, Daniel Joner; Fontoura, Roberta; Meira, Stela Maris Meister; Segalin, Jeferson; Brandelli, Adriano

    2014-11-01

    Enzymatic proteolysis may be employed to release bioactive peptides, which have been investigated for potential benefits from both technological and human health perspectives. In this study, sheep cheese whey (SCW) was hydrolyzed with a protease preparation from Bacillus sp. P7, and the hydrolysates were evaluated for antioxidant and angiotensin I-converting enzyme (ACE)-inhibitory activities. Soluble protein and free amino acids increased during hydrolysis of SCW for up to 4h. Antioxidant activity of hydrolysates, evaluated by the 2,2'azino-bis-(3-ethylbenzothiazoline)-6-sulfonic acid radical scavenging method, increased 3.2-fold from 0 h (15.9%) to 6h of hydrolysis (51.3%). Maximum Fe(2+) chelation was reached in 3h hydrolysates, and the reducing power peaked at 1h of hydrolysis, representing 6.2 and 2.1-fold increase, respectively, when compared to that of non-hydrolyzed SCW. ACE inhibition by SCW (12%) was improved through hydrolysis, reaching maximal values (55% inhibition) in 4h, although 42% inhibition was already observed after 1h hydrolysis. The peptide LAFNPTQLEGQCHV, derived from β-lactoglobulin, was identified from 4-h hydrolysates. Such a biotechnological approach might be an interesting strategy for SCW processing, potentially contributing to the management and valorization of this abundant dairy byproduct. PMID:25218972

  12. Effect of Antiviral Therapy on Serum Activity of Angiotensin Converting Enzyme in Patients with Chronic Hepatitis C

    Husic-Selimovic, Azra; Sofic, Amela; Huskic, Jasminko; Bulja, Deniz

    2016-01-01

    Introduction: Renin-angiotenzin system (RAS) is frequently activated in patients with chronic liver disease. Angiotenzin - II (AT-II), produced by angiotenzin converting enzyme (ACE), has many physiological effects, including an important role in liver fibrogenesis. Combined antiviral therapy with PEG-IFN and ribavirin besides its antiviral effect also leads to a reduction in liver parenchyma fibrosis. Aim of the study: Determining the value of ACE in serum of patients with chronic hepatitis C before and after combined antiviral therapy, as well as the value of ACE activities in sera of the control group. Materials and methods: We studied 50 patients treated at Gastroenterohepatology Department, in the time-period of four years. Value of ACE in serum was determined by Olympus AU 400 device, with application of kit “Infinity TN ACE Liquid Stable Reagent”. HCV RNA levels in sera were measured by real time PCR. HCV RNA test was performed with modular analysis of AMPLICOR and COBAS AMPLICOR HCV MONITOR test v2.0, which has proved infection and was used for quantification of the viruses and monitoring of the patients’ response to therapy. Liver histology was evaluated in accordance with the level of necroinflammation activity and stage of fibrosis. Results: Serum activities of ACE in chronic hepatitis C patients is statistically higher than the values in the control group (p=0.02). Antiviral therapy in chronic hepatitis C patients statistically decreases serum activities of ACE (p= 0.02) and indirectly affects fibrogenesis of the liver parenchyma. Correlation between ACE and ALT activity after the therapy was proved (0.3934). Conclusion: Our findings suggest that the activity of ACE in serum is a good indirect parameter of the liver damage, and could be used as an indirect prognostic factor of the level of liver parenchyma damage. Serum activity of ACE can be used as a parameter for non-invasive assessment of intensity of liver damage. PMID:27147779

  13. Preparation of bioactive peptides with high angiotensin converting enzyme inhibitory activity from winged bean [Psophocarpus tetragonolobus (L.) DC.] seed.

    Wan Mohtar, Wan Abd Al-Qadr Imad; Hamid, Azizah Abdul; Abd-Aziz, Suraini; Muhamad, Sharifah Kharidah Syed; Saari, Nazamid

    2014-12-01

    Winged bean [Psophocarpus tetragonolobus (L.) DC.] seed is a potential underexploited source of vegetable protein due to its high protein content. In the present work, undefatted and defatted winged bean seed hydrolysates, designated as UWBSH and DWBSH, respectively were produced separately by four proteolytic enzymes namely Flavourzyme, Alcalase, Bromelain, and Papain using pH-stat method in a batch reactor. Enzymatic hydrolysis was carried out over a period of 0.5 to 5 h. UWBSH and DWBSH produced were tested for their ACE inhibitory activity in relation to the hydrolysis time and degree of hydrolysis (DH). Maximum ACE inhibitory activity, both for UWBSH and DWBSH, were observed during 3 to 5 h of hydrolysis. Both, UWBSH (DH 91.84 %), and DWSBH (DH 18.72 %), produced by Papain at 5 h hydrolysis, exhibited exceptionally high ACE inhibitory activity with IC50 value 0.064 and 0.249 mg mL(-1), respectively. Besides, papain-produced UWBSH and DWBSH were further fractionated into three fractions based on molecular weight (UWBSH-I, <10 kDa; UWBSH-II, <5 kDa; UWBSH-III, <2 kDa) and (DWBSH-I, <10 kDa; DWBSH-II, <5 kDa; DWBSH-III, <2 kDa). UWBSH-III revealed the highest ACE inhibitory activity (IC50 0.003 mg mL(-1)) compared with DWBSH-III (IC50 0.130 mg mL(-1)). The results of the present investigation revealed that winged bean seed hydrolysates can be explored as a potential source of ACE inhibitory peptides suggesting their uses for physiological benefits as well as for other functional food applications. PMID:25477632

  14. Intrarenal alterations of the angiotensin-converting enzyme type 2/angiotensin 1-7 complex of the renin-angiotensin system do not alter the course of malignant hypertension in Cyp1a1-Ren-2 transgenic rats.

    Husková, Zuzana; Kopkan, Libor; Červenková, Lenka; Doleželová, Šárka; Vaňourková, Zdeňka; Škaroupková, Petra; Nishiyama, Akira; Kompanowska-Jezierska, Elzbieta; Sadowski, Janusz; Kramer, Herbert J; Červenka, Luděk

    2016-04-01

    The role of the intrarenal renin-angiotensin system (RAS) in the pathophysiology of malignant hypertension is not fully understood. Accumulating evidence indicates that the recently discovered vasodilator axis of the RAS, angiotensin-converting enzyme (ACE) type 2 (ACE2)/angiotensin 1-7 (ANG 1-7), constitutes an endogenous system counterbalancing the hypertensiogenic axis, ACE/angiotensin II (ANG II)/AT1 receptor. This study aimed to evaluate the role of the intrarenal vasodilator RAS axis in the pathophysiology of ANG II-dependent malignant hypertension in Cyp1a1-Ren-2 transgenic rats. ANG II-dependent malignant hypertension was induced by 13 days' dietary administration of indole-3-carbinol (I3C), a natural xenobiotic that activates the mouse renin gene in Cyp1a1-Ren-2 transgenic rats. It was hypothesized that pharmacologically-induced inhibition of the ACE2/ANG 1-7 complex should aggravate, and activation of this axis should attenuate, the course of ANG II-dependent malignant hypertension. Blood pressure (BP) was monitored by radiotelemetry. ACE2 inhibitor (DX 600, 0.2 μg/day) and ACE2 activator (DIZE, 1 mg/day) were administrated via osmotic minipumps. Even though ACE2 inhibitor significantly decreased and ACE2 activator increased intrarenal ANG 1-7 concentrations, the course of BP, as well as of albuminuria, cardiac hypertrophy and renal glomerular damage, were not altered. It was shown that intrarenal alterations in the ACE2/ANG 1-7 complex did not significantly modify the course of malignant hypertension in I3C-induced Cyp1a1-Ren-2 transgenic rats. Thus, in our experimental setting alterations of this intrarenal vasodilator complex of the RAS do not significantly modify the form of malignant hypertension that clearly depends on the inappropriately increased activity of the ACE/ANG II/AT1 receptor axis. PMID:26833491

  15. Angiotensin-converting enzyme gene deletion polymorphism determines an increase in frequency of migraine attacks in patients suffering from migraine without aura.

    Paterna, S; Di Pasquale, P; D'Angelo, A; Seidita, G; Tuttolomondo, A; Cardinale, A; Maniscalchi, T; Follone, G; Giubilato, A; Tarantello, M; Licata, G

    2000-01-01

    Many authors have reported an association between the angiotensin-converting enzyme (ACE)-D allele and coronary heart disease and other cardiovascular diseases. The mechanism underlying the positive associations between the ACE-D alleles and diseases are not yet clear. Previous reports showed an association between migraine without aura and ACE-D allele polymorphism. The study is aimed to evaluate if the DD genotype could also be associated with the frequency and duration of migraine without aura. In 302 patients suffering from migraine without aura (at least for 1 year), with no history of cardiovascular diseases and major risk factors for ischemic events, the genotypes of the ACE gene, plasma ACE activity, and the frequency (weekly) and duration of migraine attacks were evaluated. No drugs were given before (4 weeks) and during the study. The same evaluations were performed in 201 subjects without migraine. The molecular biologist and the physician evaluating the patient data were blinded to the clinical history and ACE-DD gene determination. Genotypes were determined by polymerase chain reaction amplification. Plasma ACE activity was performed by the HPLC method. The groups were similar for sex, age and smoking habit (migraines: 302 patients (200 F/102 M), mean age 37.8 +/- 8.2 years; control: 201 subjects (127 F/74 M), mean age 37.5 +/- 9.3 years). Patients with migraine without aura showed higher incidence of the ACE-DD gene (48.34%) than control subjects (37.32%), p < 0.05. The frequency of migraine (average attacks per week) was higher in patients with DD (2.11 +/- 1.9) than in patients with ID (1.54 +/- 1. 44), p < 0.05. No difference in duration of migraine attacks (hours per week) was observed. Plasma ACE activity was increased in patients with the ACE-DD gene. Our data suggest that ACE-DD gene polymorphism could have an important role in determining migraine attacks and the frequency of these attacks. Further data are needed through further studies

  16. Value of Angiotensin-Converting Enzyme and Monoxide Nitrogen in Pathogenesis of Myocardium Remodeling Depending on Genes' Polymorphism of Асе (I/D) and eNOS (894T>G) in Patients with Arterial Hypertension

    Sydorchuk L.P.; Gaborec I.Y.; Sydorchuk A.R.; Bukach O.P.; Sokolenko A.A.; Ursuliak J.V.; Ivaschuk S.I.; Antoniuk M.V.; Yarynych J.M.

    2013-01-01

    Introduction: Humans genes mutations in altered social conditions through interaction with environmental factors and harmful habits become an individual risk factor. Objectives: To evaluate Angiotensin-Converting Enzyme (ACE) and nitrogen monoxide metabolites (NO/NO2-/NO3-) blood levels depending on I/D polymorphism of ACE gene (dbSNP id:rs4646994), 894T>G of Endothelial Nitric Oxide Synthase (eNOS, dbSNP id:rs1799983) in pathogenesis of left ventricular hypertrophy (LVH) in patients with Ess...

  17. Effects of angiotensin converting enzyme inhibitor: ramipril on different biochemical parameters in essential hypertensive patients

    Pratibha S. Salve

    2016-06-01

    Conclusions: Ramipril has beneficial effects on RAS (Renin angiotensin system and kinin system or both may contribute to the improvement in different biochemical parameters by ramipril. [Int J Res Med Sci 2016; 4(6.000: 2288-2291

  18. ORGANOPROTECTIVE EFFECTS OF THE FIXED COMBINATION OF ANGIOTENSIN-CONVERTING ENZYME INHIBITOR LISINOPRIL AND DIURETIC HYDROCHLOROTHIAZIDE

    E. A. Ryabikhin

    2016-01-01

    Full Text Available Aim. To compare the antihypertensive and metabolic effects of combined therapy (carvedilol reception and «School of the hypertensive patient» with these of the carvedilol monotherapy in young patients with arterial hypertension (HT of 1-2 degrees with overweight and obesity.Material and methods. 63 out-patients with HT of 1-2 degrees (aged 18-27 y.o. with overweight and obesity were included in the open parallel randomized clinical preventive trail. Patients wеre randomized into 2 groups. All hypertensive patients received the carvedilol (Vedicardol, Sintez, Russia 25 mg daily. Carvedilol dose was enlarged twice in case of insufficient antihypertensive effect. Patients of the main group (n=32 also passed through the special educational program «School for hypertensive patients». Changes in blood pressure (BP level, body mass index, biochemical markers and risk factors were evaluated initially and in 24 weeks of therapy.Results. Patients of the main group had more significant risk factor manifestations decrease than in group of comparison. More significant body mass index decrease was also observed in the main group in comparison with group of comparison: from 32,5±0,4 to 26,4±0,7 kg/m2 (p<0,01 and from 31,8±0,8 to 28,9±1,18 kg/m2 (p<0,05, respectively. In patients of the main group systolic and diastolic BP decreased by 20,1% and 25,6%, respectively, wile in patients of the group of comparison – by 18,9% and 26%, respectively.Conclusion. It is reasonable to combine carvedilol therapy with special training in the young hypertensive patients with overweight and obesity.

  19. Use of different types of angiotensin converting enzyme inhibitors and mortality in systolic heart failure

    Svanström, Henrik; Pasternak, Björn; Melbye, Mads;

    2015-01-01

    on the comparable effectiveness of different ACEIs is scarce. We conducted a registry-based cohort study to assess all-cause mortality associated with the use of enalapril, perindopril, and trandolapril, as compared with ramipril, in patients with systolic HF. METHODS: Patients with systolic HF (EF ≤40%), 2003......-2012, were identified using the Danish HF Registry. New users of enalapril (n=1807), perindopril (n=1064), ramipril (n=3270), or trandolapril (n=1150), who started treatment within 60days of first-time hospital diagnosis of HF, were selected for inclusion. Subgroup analyses were conducted by sex, age, NYHA......-level, EF, and ischemic heart disease. All analyses were adjusted for empirical risk scores for mortality. RESULTS: During follow-up, 291 deaths were observed among users of enalapril (incidence rate per 100person-years [IR], 10.1), 212 among users of perindopril (IR, 10.5), 568 among users of ramipril (IR...

  20. Radiation nephropathy in rats and its modification by the angiotensin converting enzyme inhibitor enalapril

    The ability of prophylactic enalapril treatment to prevent or retard the development of radiation-induced nephropathy was studied in male Wistar rats. Prior to irradiation, the rats were randomized to groups receiving enalapril or no treatment, and both kidneys of rats were irradiated with either a 10 Gy single dose or 26 Gy at a rate of 2 Gy per fraction per day. Renal function was assessed prior to radiotherapy and at intervals of 8 weeks thereafter. A subgroup of animals was sacrificed for histopathology at 4, 8, 16, and 24 weeks after irradiation. At 16 weeks after irradiation, renal function showed deterioration without any significant differences between groups. At 24 weeks after irradiation, all irradiation dose groups with or without enalapril treatment showed some improvement in functional terms. Morphological evaluation revealed that enalapril had a marked beneficial effect on renal radiation injury in the 10 Gy single-dose group and at 8 weeks after irradiation. At 16 weeks after irradiation the histological appearance of the dose groups with or without enalapril treatment was similar. We conclude that enalapril, when used preventively from the time of irradiation, has a beneficial effect only after high doses per fraction and at the early phases of renal radiation injury. (author)

  1. Angiotensin converting enzyme (ACE DD genotype: relationship with venous thrombosis Genótipo DD da enzima conversora de angiotensina (ECA: relação com trombose venosa

    Terezinha P. Munhoz

    2005-06-01

    Full Text Available Venous thromboembolism is a common multifactorial disease associated with acquired and inherited predisposing factors. Several polymorphisms, e.g. factor V Leiden, factor II G20210A and deficiency of antithrombin, protein C and protein S, have been associated with venous thromboembolism. Angiotensin converting-enzyme affects hemostasis by decreasing fibrinolysis. Angiotensin converting-enzyme gene polymorphism, a 287 pb insertion/deletion at introns 16, is related to variations in enzyme serum levels. The DD genotype has been associated with increased risk for venous thrombosis. This study examined the frequency of the angiotensin converting-enzyme alleles I and D and their association with venous thrombosis in a group of individuals from the south of Brazil. Seventy-one patients with deep venous thrombosis and/or pulmonary thromboembolism and 71 healthy individuals were analysed in a case-control study. The angiotensin converting-enzyme ID genotyping was performed by polymerase chain reaction. The frequencies of the D allele and DD genotype were, respectively, 51.4% and 22.5% for patients, and 64.7% and 45.0% for controls. The Odds Ratio for the dominant hypothesis (DD+ID versus II genotypes was 0. 75 (CI 95%; 0.29-1.93 and the Odds Ratio for recessive hypothesis (DD versus ID+II was 0.35 (CI 95%; 0.16-0.78. In conclusion, our results indicate a protective effect of the angiotensin converting-enzyme DD genotype on venous thromboembolism.O troemboembolismo venoso (TEV é uma doença multifatorial associada com fatores de risco adquiridos e hereditários. Vários polimorfismos, tais como fator V de Leiden, mutação G20210A da protrombina e as deficiências de proteína C, proteína S e anti-trombina são considerados fatores de risco para TEV. A enzima conversora da angiotensina (ECA afeta a hemostasia diminuindo a fibrinólise. O polimorfismo no gene da ECA, caracterizado pela inserção/deleção de um fragmento de 287 pb no intron16, est

  2. Pulmonary Embolism in a Sarcoidosis Patient Double Heterozygous for Methylenetetrahydrofolate Reductase Gene Polymorphisms and Factor V Leiden and Homozygous for the D-Allele of Angiotensin Converting Enzyme Gene

    Nadim El-Majzoub

    2015-01-01

    Full Text Available Sarcoidosis is a multisystem granulomatous disease of unknown etiology and pathogenesis. It presents in patients younger than 40 years of age. The lungs are the most commonly affected organ. Till the present day, there is no single specific test that will accurately diagnose sarcoidosis; as a result, the diagnosis of sarcoidosis relies on a combination of clinical, radiologic, and histologic findings. Patients with sarcoidosis have been found to have an increased risk of pulmonary embolism compared to the normal population. MTHFR and factor V Leiden mutations have been reported to increase the risk of thrombosis in patients. We hereby present a case of a middle aged man with sarcoidosis who developed a right main pulmonary embolism and was found to be double heterozygous for methylenetetrahydrofolate reductase gene polymorphisms and factor V Leiden and homozygous for the D-allele of the angiotensin converting enzyme gene.

  3. Association of Angiotensin-Converting Enzyme Intron 16 Insertion/Deletion and Angiotensin II Type 1 Receptor A1166C Gene Polymorphisms with Preeclampsia in South East of Iran

    Saeedeh Salimi

    2011-01-01

    Full Text Available Some evidence suggests that a variety of genetic factors contributed in pathogenesis of the preeclampsia. The aim of this study was to assess the association between the angiotensin-converting enzyme (ACE I/D and angiotensin II type1 receptor A1166C polymorphisms with preeclampsia. This study was performed in 125 preeclamptic pregnant women and 132 controls. The I/D Polymorphism of the ACE gene was assessed by polymerase chain reaction and the A1166C Polymorphism of the AT1R gene was determined by restriction fragment length polymorphism. The genotype and allele frequencies of I/D polymorphism differed between two groups. The risk of preeclampsia was 3.2-fold in pregnant women with D allele (OR, 3.2 [95% CI, 1.1 to 3.8]; P=0.01. The distribution of the AT1R gene A1166C polymorphism was similar in affected and control groups. Our results supported that presence of the I/D polymorphism of ACE gene is a marker for the increased risk of preeclampsia.

  4. In vitro investigations of the potential health benefits of Australian-grown faba beans (Vicia faba L.): chemopreventative capacity and inhibitory effects on the angiotensin-converting enzyme, α-glucosidase and lipase.

    Siah, Siem D; Konczak, Izabela; Agboola, Samson; Wood, Jennifer A; Blanchard, Christopher L

    2012-08-01

    The functional properties, including antioxidant and chemopreventative capacities as well as the inhibitory effects on angiotensin-converting enzyme (ACE), α-glucosidase and pancreatic lipase, of three Australian-grown faba bean genotypes (Nura, Rossa and TF(Ic*As)*483/13) were investigated using an array of in vitro assays. Chromatograms of on-line post column derivatisation assay coupled with HPLC revealed the existence of active phenolics (hump) in the coloured genotypes, which was lacking in the white-coloured breeding line, TF(Ic*As)*483/13. Roasting reduced the phenolic content, and diminished antioxidant activity by 10-40 % as measured by the reagent-based assays (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and oxygen radical absorbance capacity) in all genotypes. Cell culture-based antioxidant activity assay (cellular antioxidant activity) showed an increase of activity in the coloured genotypes after roasting. Faba bean extracts demonstrated cellular protection ability against H₂O₂-induced DNA damage (assessed using RAW264.7 cells), and inhibited the proliferation of all human cancer cell lines (BL13, AGS, Hep G2 and HT-29) evaluated. However, the effect of faba bean extracts on the non-transformed human cells (CCD-18Co) was negligible. Flow cytometric analyses showed that faba bean extracts successfully induced apoptosis of HL-60 (acute promyelocytic leukaemia) cells. The faba bean extracts also exhibited ACE, α-glucosidase and pancreatic lipase inhibitory activities. Overall, extracts from Nura (buff-coloured) and Rossa (red-coloured) were comparable, while TF(Ic*As)*483/13 (white-coloured) contained the lowest phenolic content and exhibited the least antioxidant and enzyme inhibition activities. These results are important to promote the utilisation of faba beans in human diets for various health benefits. PMID:22916808

  5. New perspectives in the renin-angiotensin-aldosterone system (RAAS III: endogenous inhibition of angiotensin converting enzyme (ACE provides protection against cardiovascular diseases.

    Miklós Fagyas

    Full Text Available ACE inhibitor drugs decrease mortality by up to one-fifth in cardiovascular patients. Surprisingly, there are reports dating back to 1979 suggesting the existence of endogenous ACE inhibitors. Here we investigated the clinical significance of this potential endogenous ACE inhibition. ACE concentration and activity was measured in patient's serum samples (n = 151. ACE concentration was found to be in a wide range (47-288 ng/mL. ACE activity decreased with the increasing concentration of the serum albumin (HSA: ACE activity was 56 ± 1 U/L in the presence of 2.4 ± 0.3 mg/mL HSA, compared to 39 ± 1 U/L in the presence of 12 ± 1 mg/mL HSA (values are mean ± SEM. Effects of the differences in ACE concentration were suppressed in human sera: patients with ACE DD genotype exhibited a 64% higher serum ACE concentration (range, 74-288 ng/mL, median, 155.2 ng/mL, n = 52 compared to patients with II genotype (range, 47-194 ng/mL, median, 94.5 ng/mL, n = 28 while the difference in ACE activities was only 32% (range, 27.3-59.8 U/L, median, 43.11 U/L, and range 15.6-55.4 U/L, median, 32.74 U/L, respectively in the presence of 12 ± 1 mg/mL HSA. No correlations were found between serum ACE concentration (or genotype and cardiovascular diseases, in accordance with the proposed suppressed physiological ACE activities by HSA (concentration in the sera of these patients: 48.5 ± 0.5 mg/mL or other endogenous inhibitors. Main implications are that (1 physiological ACE activity can be stabilized at a low level by endogenous ACE inhibitors, such as HSA; (2 angiotensin II elimination may have a significant role in angiotensin II related pathologies.

  6. Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure

    McMurray, John J V; Packer, Milton; Desai, Akshay S;

    2013-01-01

    AIMS: Although the focus of therapeutic intervention has been on neurohormonal pathways thought to be harmful in heart failure (HF), such as the renin-angiotensin-aldosterone system (RAAS), potentially beneficial counter-regulatory systems are also active in HF. These promote vasodilatation and...... natriuresis, inhibit abnormal growth, suppress the RAAS and sympathetic nervous system, and augment parasympathetic activity. The best understood of these mediators are the natriuretic peptides which are metabolized by the enzyme neprilysin. LCZ696 belongs to a new class of drugs, the angiotensin receptor...

  7. Bioactivity comparison of extracts from various parts of common and tartary buckwheats: evaluation of the antioxidant- and angiotensin-converting enzyme inhibitory activities

    Tsai Hweiyan

    2012-08-01

    Full Text Available Abstract Background Buckwheat flour and buckwheat sprouts possess antioxidant properties, and previous studies have reported on buckwheat flour displaying an inhibitory activity for angiotensin-I converting enzyme (ACE. Information is lacking on the bioactivity of other parts of the buckwheat, such as the seed hulls and plant stalks. This study investigates the ACE inhibitory activity and antioxidant activity of various parts of 2 types of buckwheat, namely, common buckwheat (Fagopyrum esculentum Moench and tartary buckwheat (Fagopyrum tataricum Gaertn. Results The extract of common hulls extracted using 50% (v/v-ethanol solvent presented a remarkable inhibitory activity. The value of IC50 is 30 μg ml-1. The extracts of both common and tartary hulls extracted using 50% (v/v-ethanol solvent demonstrated an antioxidant activity that is superior to that of other extracts. Conclusion This study determined that the ethanolic extract of the hulls of common buckwheat presented more favorable antioxidant and ACE inhibitory abilities. However, the correlation of antioxidant activity and ACE inhibitory activity for all 18 types of extracts is low. The ACE inhibitory activity could have been caused by a synergistic effect of flavonoids or from other unidentified components in the extracts. The ethanolic extract of common hulls demonstrated remarkable ACE inhibitory activity and is worthy of further animal study.

  8. Sex differences in renal angiotensin converting enzyme 2 (ACE2 activity are 17β-oestradiol-dependent and sex chromosome-independent

    Liu Jun

    2010-11-01

    Full Text Available Abstract Background Angotensin converting enzyme 2 (ACE2 is a newly discovered monocarboxypeptidase that counteracts the vasoconstrictor effects of angiotensin II (Ang II by converting Ang II to Ang-(1-7 in the kidney and other tissues. Methods ACE2 activity from renal homogenates was investigated by using the fluorogenic peptide substrate Mca-YVADAPK(Dnp-OH, where Mca is (7-methoxycoumarin-4-yl-acetyl and Dnp is 2,4-dinitrophenyl. Results We found that ACE2 activity expressed in relative fluorescence units (RFU in the MF1 mouse is higher in the male (M compared to the female (F kidney [ACE2 (RFU/min/μg protein: M 18.1 ± 1.0 versus F 11.1 ± 0.39; P n = 6]. Substrate concentration curves revealed that the higher ACE2 activity in the male was due to increased ACE2 enzyme velocity (Vmax rather than increased substrate affinity (Km. We used the four core genotypes mouse model in which gonadal sex (ovaries versus testes is separated from the sex chromosome complement enabling comparisons among XX and XY gonadal females and XX and XY gonadal males. Renal ACE2 activity was greater in the male than the female kidney, regardless of the sex chromosome complement [ACE2 (RFU/min/μg protein: intact-XX-F, 7.59 ± 0.37; intact-XY-F, 7.43 ± 0.53; intact-XX-M, 12.1 ± 0.62; intact-XY-M, 12.7 ± 1.5; n = 4-6/group; P n = 6/group]. 17β-oestradiol (E2 treatment of GDX mice resulted in ACE2 activity that was only 40% of the activity found in the GDX mice, regardless of their being male or female, and was independent of the sex chromosome complement [ACE2 (RFU/min/μg protein: GDX+E2-XX-F, 5.56 ± 1.0; GDX+E2-XY-F, 4.60 ± 0.52; GDX+E2-XX-M, 5.35 ± 0.70; GDX+E2-XY-M, 5.12 ± 0.47; n = 6/group]. Conclusions Our findings suggest sex differences in renal ACE2 activity in intact mice are due, at least in part, to the presence of E2 in the ovarian hormone milieu and not to the testicular milieu or to differences in sex chromosome dosage (2X versus 1X; 0Y versus 1Y

  9. The Interaction Between Angiotensin Converting Enzyme Inhibitor (Captopril and Heat Stress in The Male Albino rats. 2-Tissue Analysis

    Talaat E.I. Abd-Rabo

    2000-12-01

    Full Text Available Daily exposure to heat stress causes sustained elevation of blood pressure in rats. It is known that the renin-angiotensin system is activated during episodes of behavioral stress, and the purpose of this work was to assess the action of captopril in the development of stress induced hypertension in rats. Animals were divided into four groups. The first group served as a control, while the other groups were subjected to heat stress of 40C and high hamidity of 80% for 10 successive days. The second group was served as heat stress, while the third and the fourth groups were received low and high doses of captopril (0.7 & 1.4 mg/kg. b.wt., respectively. After 10 days of treatment, half of animals from each group were decapitated and brain, liver, muscle, heart and kidney were separated and analysed. The other half of animals were left for another 10 days without any additional treatment for recovery.The results revealed a significant decrease in total protein of liver, heart, kidney, total lipids of heart, muscle and brain and total cholesterol of liver. On the other hand, insignificant change was noticed in muscle and brain total protein. Similarly, AST and ALT activities were also within the normal values for all the organs examined.Results exhibited that renin-angiotensin system may be important in the development of stress-induced hypertension in rats.

  10. Combination of the angiotensin-converting enzyme inhibitor perindopril and the diuretic indapamide activate postnatal vasculogenesis in spontaneously hypertensive rats

    D. You (Dong); C. Cochain (Clément); C. Loinard (Céline); J. Vilar (Jose Manuel); B.M.E. Mees (Barend); M. Duriez (Micheline); B.I. Levy (Bernard); J.S. Silvestre (Jean Sebastien)

    2008-01-01

    textabstractCardiovascular risk factors are associated with reduction in both the number and function of vascular progenitor cells. We hypothesized that 1) hypertension abrogates postnatal vasculogenesis, and 2) antihypertensive treatment based on the combination of perindopril (angiotensin-converti

  11. Cognitive enhancing effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on learning and memory

    V S Nade

    2015-01-01

    Conclusion: The results suggest that the cognitive enhancing effect of ACEI and ARBs may be due to inhibition of AChE or by regulation of antioxidant system or increase in formation of angiotensin IV.

  12. Antidiabetic mechanisms of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists: beyond the renin-angiotensin system

    Kurtz, T. W.; Pravenec, Michal

    2004-01-01

    Roč. 22, č. 12 (2004), s. 2253-2261. ISSN 0263-6352 R&D Projects: GA ČR GA301/03/0751 Grant ostatní: HHMI(US) HHMI55000331 Institutional research plan: CEZ:AV0Z5011922 Keywords : angiotensin II receptors * metabolic syndrome * peroxisome proliferator activated receptors Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.871, year: 2004

  13. Clopidogrel Bioactivation and Risk of Bleeding in Patients Cotreated With Angiotensin-Converting Enzyme Inhibitors After Myocardial Infarction

    Kristensen, Karl E.; Zhu, Hao-Jie; Wang, Xinwen;

    2014-01-01

    clinically significant bleeding in ACEI-treated patients cotreated with or without clopidogrel were 1.10 (95% confidence interval (CI): 0.97-1.25, P = 0.124) and 0.90 (95% CI: 0.81-0.99, P = 0.025), respectively, as compared with patients who did not receive ACEIs. This difference was statistically...

  14. Role of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in hypertension of chronic kidney disease and renoprotection. Study results

    Baltatzi, M; Savopoulos, Ch; Hatzitolios, A

    2011-01-01

    Chronic kidney disease (CKD) is a global health problem associated with considerable morbidity and mortality and despite advances in the treatment of end stage renal disease (ESRD) mechanisms to prevent and delay its progression are still being sought. The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in many of the pathophysiologic changes that lead to progression of renal disease. Traditionally RAAS was considered as an endocrine system and its principal role was to maint...

  15. Value of Angiotensin-Converting Enzyme and Monoxide Nitrogen in Pathogenesis of Myocardium Remodeling Depending on Genes' Polymorphism of Асе (I/D and eNOS (894T>G in Patients with Arterial Hypertension

    Sydorchuk L.P.

    2013-03-01

    Full Text Available Introduction: Humans genes mutations in altered social conditions through interaction with environmental factors and harmful habits become an individual risk factor. Objectives: To evaluate Angiotensin-Converting Enzyme (ACE and nitrogen monoxide metabolites (NO/NO2-/NO3- blood levels depending on I/D polymorphism of ACE gene (dbSNP id:rs4646994, 894T>G of Endothelial Nitric Oxide Synthase (eNOS, dbSNP id:rs1799983 in pathogenesis of left ventricular hypertrophy (LVH in patients with Essential Arterial Hypertension (EAH. Methods: 120 screened patients with EAH I-III stages (48.3% – women, 51.7% – men, average age 52.9±9.24 years and 40 healthy persons participated in prospective study. Alleles of polymorphic locus were studied by PCR method. Serum ACE level was detected by ELISA. Plasma NO metabolites levels were determined by colorimetric method. Structural myocardium changes – by EchoCG, ECG. Results analyzed according to the European guidelines ESC/ESH (2009.Results: D-allele presence (ACE associated with high risk of LVH geometric patterns and higher level of ACE. Presence of TT-genotype of eNOS gene (ID/TT-haplotype associated with lower levels of NO metabolites by 14.5% (р<0.05. Homozygous D-allele carriers (regardless of genotypes combination of eNOS gene – DD/TG, DD/GG haplotypes have ACE concentration increased by 18.1% and 17.5%, accordingly (р<0.05. The absence of mutations in haplotypes (II/GG is a protective factor against LVH (OR=0.13, p=0.047, with the lowest level of ACE, followed by higher concentration of NO metabolites (p<0.05. The combination of D+T allele in haplotypes (ID/TG, DD/TG increases the relative risk of LVH and EAH II and III in 1.19-2.25 times (OR=4.75-13.5, p≤0.021-0.001, which is confirmed by severity of clinical course, and increased ACE serum level (DD/TG carriers.Conclusion: Risk groups for eccentric or concentric LVH models are D-allele carriers (ACE gene with highest ACE level and T-allele of e

  16. The effect of CCR2 inhibitor CCX140-B on residual albuminuria in patients with type 2 diabetes and nephropathy : a randomised trial

    de Zeeuw, Dick; Bekker, Pirow; Henkel, Elena; Hasslacher, Christopher; Gouni-Berthold, Ioanna; Mehling, Heidrun; Potarca, Antonia; Tesar, Vladimir; Lambers Heerspink, Hiddo J.; Schall, Thomas J.

    2015-01-01

    Background Patients with type 2 diabetes and nephropathy have high cardiorenal morbidity and mortality despite optimum treatment including angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Residual risk is related to residual albuminuria. We assessed whether CCX

  17. Icatibant er en ny behandlingsmulighed ved livstruende angiotensinkonverterende enzym-inhibitor-udløst angioødem

    Fast, Søren; Henningsen, Emil; Bygum, Anette

    2011-01-01

    A 78 year-old woman with life-threatening angiotensin-converting enzyme inhibitor (ACE-i) induced angioedema was unresponsive to conventional treatment with corticosteroids, antihistamines and epinephrine. She was successfully treated with icatibant licensed for treatment of hereditary angioedema...... knowing that both conditions involve bradykinin induced activation of bradykinin B2 receptors. Randomised, controlled trials are warranted to document the efficacy of icatibant in ACE-i angioedema....

  18. Influência do uso crônico dos inibidores da enzima conversora da angiotensina na hipotensão arterial após indução anestésica: é necessário suspender esse fármaco no pré-operatório? Influencia del uso crónico de los inhibidores de la enzima conversora de la angiotensina en la hipotensión arterial después de la inducción anestésica: ¿es necesario suspender ese fármaco en el preoperatorio? Influence of angiotensin-converting enzyme inhibitors on hypotension after anesthetic induction: is the preoperative discontinuation of this drug necessary?

    Verônica Vieira da Costa

    2009-12-01

    anestesia. Como controles fueron seleccionados pacientes de la misma franja etaria y sexo, sometidos a la intervención quirúrgica en el mismo período de los casos y que no presentaron hipotensión arterial. Las variables de interés fueron las siguientes: edad, sexo, porte quirúrgico, diagnóstico previo de hipertensión arterial sistémica (HAS, uso de IECA, estado físico (ASA, sangramiento en el intraoperatorio, técnica anestésica y tiempo quirúrgico. RESULTADOS: Cuarenta pacientes presentaron hipotensión arterial, en un total de 2.179 operaciones. De ellos, 20 usaron IECA el día de la operación. El grupo control estuvo compuesto por 171 pacientes, de los cuales 11 usaron IECA. En el análisis univariado, se encontró una asociación entre la hipotensión arterial y la edad avanzada (p BACKGROUND AND OBJECTIVES: The discontinuation of drugs such as angiotensin-converting enzyme inhibitors (ACE inhibitors has been suggested based on reports of hypotension during anesthesia. This may imply on a higher risk of intraoperative hypertensive peaks with deleterious consequences for the patient. The objective of the present study was to evaluate the influence of the preoperative use of ACE inhibitors on the development of hypotension during anesthesia. METHODS: This is a case-controlled study of patients who developed hypotension after anesthetic induction. The control group was composed of patients of the same age and gender who underwent surgeries during the same period and who did not develop hypotension. Parameters of interest included: age, gender, size of the surgery, prior diagnosis of hypertension, use of ACE inhibitors, physical status (ASA, intraoperative bleeding, anesthetic technique, and duration of the surgery. RESULTS: In 2,179 surgeries, 40 patients developed hypotension. Twenty of those patients used ACEIs on the day of the surgery. The control group was composed by 171 patients, 11 of which used ACE inhibitors. Univariate analysis showed an association

  19. 高效液相色谱法测定霉茶成分及其对血管紧张肽转化酶的抑制作用%Determination of Components from Ampelopsis Grossedentata by HPLC and Inhibitory Effect of Its on Angiotensin Converting Enzyme

    吴勇; 罗弘; 王瑞; 谭永霞; 胡俊杰; 张宝徽; 田先翔; 郑国华; 张筱祎

    2015-01-01

    目的 利用高效液相色谱法测定霉茶成分对血管紧张肽转化酶( ACE)的抑制作用. 方法 以马尿酰-组氨酰-亮氨酸( HHL)为反应底物,经ACE催化生成的马尿酸为测定指标,分别考察霉茶总黄酮、二氢杨梅素、杨梅素对ACE的抑制作用. 采用Welchrom C18色谱柱(4.6 mm×250 mm,5 μm),流动相为水(含0.1%甲酸,0.1%三乙胺):乙腈(含0.1%甲酸,0.1%三乙胺)=78:22,柱温30 ℃,流速1.0 mL·min-1 ,检测波长228 nm,进样量10 μL. 结果 马尿酸在0.05~5.00 μg范围内其进样量与峰面积呈良好的线性关系(r=0.999 9),霉茶总黄酮、二氢杨梅素对ACE抑制率>75%. 结论 经该法检测,霉茶总黄酮、二氢杨梅素对ACE均有较强抑制作用. 该方法简单、灵敏、重复性好,可用于ACE抑制药的体外活性筛选.%Objective To measure the inhibition of components from Ampelopsis grossedentata on angiotensin converting enzyme ( ACE) by high performance liquid chromatograph. Methods By quantitative determination of hippuric acid, the ACE-catalyzed product from the substrate HIPPURYL-HIS-LEU ( HHL) , the inhibitory effect of the total flavonoids of Ampelopsis grossedentata, dihydromyricetin and myricetin were evaluated respectively. High performance liquid chromatograph analysis was conducted on a Welchrom C18 column (4.6 mm×250 mm, 5μm), eluting with water:acetonitrile (each containing 0.1% formic acid and 0.1% triethylamine)=78:22, at flow rate of 1.0 mL·min-1 under temperature of 30℃, and the detection wavelength was set at 228 nm and the injection volume was 10 μL. Results The injection amount of hippuric acid showed good linearity with peak area within the range of 0.05-5.00 μg (r = 0.999 9), and the inhibitory rate of the total flavonoids of Ampelopsis grossedentata and dihydromyricetin reached more than 75% against ACE. Conclusion As the method exhibited, the total flavonoids of Ampelopsis grossedentata and dihydromyricetin have potent inhibition against

  20. Angioneurotisk ødem i forbindelse med behandling med angiotensinkonverterende enzym-haemmer

    Johansen, E C; Johansen, J B; Døssing, H

    1996-01-01

    Angioneurotic oedema secondary to angiotensin-converting enzyme (ACE) inhibitors is a rare condition, but it is a side effect which is likely to be seen more frequently because of the increased use of these drugs in the treatment of heart failure and hypertension. We report two cases which...... illustrate problems in the diagnosis and management of this life-threatening condition, and also demonstrate that angioedema re-occurs if the ACE inhibitor is not discontinued. If angioedema is suspected, therapy with any angiotensin converting-enzyme inhibitor should be discontinued promptly, respiratory...

  1. Dosing of ACE inhibitors in left ventricular dysfunction : Does current clinical dosing provide optimal benefit?

    Pinto, YM; van Geel, PP; Alkfaji, H; van Veldhuisen, DJ; van Gilst, WH

    1999-01-01

    In the present review, we discuss the role of clinical dosing of angiotensin converting enzyme (ACE) inhibitors in the treatment of left ventricular dysfunction. Although the precise mechanism of action of ACE inhibitors is still unresolved, the clinical efficacy of ACE inhibitors in the treatment o

  2. Angiotensin AT1-receptor blockers and cerebrovascular protection: do they actually have a cutting edge over angiotensin-converting enzyme inhibitors?

    Oprisiu-Fournier, Roxana; Faure, Sébastien; Mazouz, Hakim;

    2009-01-01

    is presented to support the hypothesis that antihypertensive drugs that increase angiotensin II formation, such as diuretics, AT1-receptor blockers and dihydropyridines, may have greater brain anti-ischemic effects than antihypertensive drugs that decrease angiotensin II formation, such as beta-blockers...

  3. Separation of angiotensin converting enzyme inhibitor peptides%血管紧张素转换酶抑制肽的分离

    曾庆祝; 许庆陵; 黄儒强; 邱礼平

    2007-01-01

    采用截留分子量分别为30 ku、10 ku、6 ku、3 ku的中空纤维超滤膜对扇贝酶解产物进行分级分离,并结合凝胶柱层析分离技术测定了各分离组分的分子量分布,同时还测定了各分离组分对血管紧张素转换酶(ACE)的抑制活性.实验结果表明,不同截留分子量超滤膜可以实现酶解产物按其分子量大小的分级分离,不同分离组分的ACE抑制力活性差异较大,总趋势是截留分子量相对较小的超滤膜透过液的ACE抑制活性较强.其中,截留分子量为3 ku超滤膜的透过液具有最强的ACE抑制活性,其ACE抑制率I(%)=96.17%,半抑制浓度IC50=0.078 mg · mL-1.通过对截留分子量为3 ku超滤膜的透过液依次经过Sephadex G-25及Sephadex G-15凝胶柱层析分离纯化后,分离出了ACE抑制活性最强的2个组分活性肽,其平均分子量分别为1 300 u和900 u左右,其IC50分别为0.026 mg · mL-1和0.012 mg · mL-1.

  4. 一种新的转换酶抑制剂--福辛普利%A Novel Angiotensin-Converting Enzyme (ACE) Inhibitor: Fosinopril

    康建华

    2000-01-01

    福辛普利(蒙诺)是其活性二价酸福辛普利拉的酯类前体药物,也是新的磷酸类血管紧张素转换酶(ACE)抑制剂家族中的第一个成员.与其它ACE抑制剂一样,福辛普利主要通过阻断血管紧张素II的形成而降低血压,该药物在原发性高血压和心力衰竭等患者中已显示其临床效果.在ACE抑制剂中,福辛普利的特点是具有肝脏、肾脏双重清除途径,两者之间能保持平衡.研究表明,对于患慢性心力衰竭,并同时患有肾脏功能不全的患者来说,福辛普利可能是一种可与其它ACE抑制剂相替换的有价值的药物.

  5. 血管紧张素转换酶抑制剂的合理选用%The rational use of angiotensin converting enzyme inhibitors

    余自成

    2001-01-01

    @@ 自1965年发现腹蛇的多肽类毒素能抑制血管紧张素转换酶(ACE)后,ACE抑制剂的研究工作进展迅速.现在国外已批准上市的ACE抑制剂有20种以上,正在研究的已超过80种.临床试验结果已显示,某些ACE抑制剂除具有降压作用外,还具有与降低血压无关的其它益处,如改善心衰症状、降低心衰病人死亡率,在急性心肌梗死后用药对不论是否有心衰的病人所产生的益处,另外,有些ACE抑制剂还具有血管保护和肾保护作用.不同ACE抑制剂在作用上既有共性,又有各自不同的特点.ACE抑制剂发展速度快,品种多,作用各有其不同的特点,这就要求临床医生对此类药物有比较全面的了解,才能比较合理地选用此类药物,使其在临床治疗中更好地发挥作用.

  6. Data of the natural and pharmaceutical angiotensin-converting enzyme inhibitor isoleucine-tryptophan as a potent blocker of matrix metalloproteinase-2 expression in rat aorta.

    Kopaliani, Irakli; Martin, Melanie; Zatschler, Birgit; Müller, Bianca; Deussen, Andreas

    2016-09-01

    The present data are related to the research article entitled "Whey peptide isoleucine-tryptophan inhibits expression and activity of matrix metalloproteinase-2 in rat aorta" [1]. Here we present data on removal of endothelium from aorta, endothelium dependent aortic relaxation and inhibition of expression of pro-MMP2 by di-peptide isoleucine-tryptophan (IW). Experiments were performed in rat aortic endothelial cells (EC) and smooth muscle cells (SMC) in vitro, along with isolated rat aorta ex vivo. The cells and isolated aorta were stimulated with angiotensin II (ANGII) or angiotensin I (ANGI). ACE activity was inhibited by treatment with either IW or captopril (CA). Losartan was used as a blocker of angiotensin type-1 receptor. IW inhibited MMP2 protein expression induced with ANGI in a dose-dependent manner. IW was effective both in ECs and SMCs, as well as in isolated aorta. Similarly, captopril (CA) inhibited ANGI-induced MMP2 protein expression in both in vitro and ex vivo. Neither IW nor CA inhibited ANGII-induced MMP2 protein expression in contrast to losartan. The data also displays that removal of endothelium in isolated rat aorta abolished the endothelium-dependent relaxation induced with acetylcholine. However, SMC-dependent relaxation induced with sodium nitroprusside remained intact. Finally, the data provides histological evidence of selective removal of endothelial cells from aorta. PMID:27508250

  7. Compliance, Persistence, and Switching Patterns for ACE Inhibitors and ARBs

    Vegter, S.; Nguyen, N.H.; Visser, S.T.; de Jong-van den Berg, LTW; Postma, M.J.; Boersma, C.

    2011-01-01

    Objectives: To investigate compliance, persistence, and switching patterns for angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). Study Design: Drug-utilization analysis using a large prescription database. Methods: Prescription data for more than 50,000 inciden

  8. Expression of apical Na(+)-L-glutamine co-transport activity, B(0)-system neutral amino acid co-transporter (B(0)AT1) and angiotensin-converting enzyme 2 along the jejunal crypt-villus axis in young pigs fed a liquid formula.

    Yang, Chengbo; Yang, Xiaojian; Lackeyram, Dale; Rideout, Todd C; Wang, Zirong; Stoll, Barbara; Yin, Yulong; Burrin, Douglas G; Fan, Ming Z

    2016-06-01

    Gut apical amino acid (AA) transport activity is high at birth and during suckling, thus being essential to maintain luminal nutrient-dependent mucosal growth through providing AA as essential metabolic fuel, substrates and nutrient stimuli for cellular growth. Because system-B(0) Na(+)-neutral AA co-transporter (B(0)AT1, encoded by the SLC6A19 gene) plays a dominant role for apical uptake of large neutral AA including L-Gln, we hypothesized that high apical Na(+)-Gln co-transport activity, and B(0)AT1 (SLC6A19) in co-expression with angiotensin-converting enzyme 2 (ACE2) were expressed along the entire small intestinal crypt-villus axis in young animals via unique control mechanisms. Kinetics of Na(+)-Gln co-transport activity in the apical membrane vesicles, prepared from epithelial cells sequentially isolated along the jejunal crypt-villus axis from liquid formula-fed young pigs, were measured with the membrane potential being clamped to zero using thiocyanate. Apical maximal Na(+)-Gln co-transport activity was much higher (p < 0.05) in the upper villus cells than in the middle villus (by 29 %) and the crypt (by 30 %) cells, whereas Na(+)-Gln co-transport affinity was lower (p < 0.05) in the upper villus cells than in the middle villus and the crypt cells. The B(0)AT1 (SLC6A19) mRNA abundance was lower (p < 0.05) in the crypt (by 40-47 %) than in the villus cells. There were no significant differences in B(0)AT1 and ACE2 protein abundances on the apical membrane among the upper villus, the middle villus and the crypt cells. Our study suggests that piglet fast growth is associated with very high intestinal apical Na(+)-neutral AA uptake activities via abundantly co-expressing B(0)AT1 and ACE2 proteins in the apical membrane and by transcribing the B(0)AT1 (SLC6A19) gene in the epithelia along the entire crypt-villus axis. PMID:26984322

  9. 血管紧张素转换酶基因rs1799752位点插入或缺失多态性与糖尿病视网膜病变的相关性研究%Relationship of angiotensin converting enzyme gene polymorphism with diabetic retinopathy

    李娜; 杨秀芬; 顾虹; 邓禹; 徐军; 马凯; 刘宁朴

    2013-01-01

    目的 探讨血管紧张素转换酶(ACE)基因rs1799752位点插入或缺失(I/D)多态性与糖尿病视网膜病变(DR)的相关性.方法 病例对照研究.选择2型糖尿病患者412例,其中DR组207例,糖尿病无视网膜病变(DWR)组205例;DR组中筛选出增生性DR (PDR)患者53例,作为PDR组;收集同源非糖尿病志愿者97例作为对照人群.采用PCR和琼脂糖凝胶电泳技术检测ACE基因rs1799752位点I/D多态性基因型.组间基因型及等位基因频率比较采用x2检验.符合正态分布的连续变量组间比较采用t检验或方差分析,不符合正态分布的连续变量组间比较采用秩和检验.对疾病发生相关因素进行logistic回归分析.结果 ACE基因rs1799752位点的I和D等位基因频率:DR组分别为54.1%和45.9%,PDR组分别为52.8%和47.2%,DWR组分别为48.0%和52.0%;DR组与DWR组、PDR组与DWR组的等位基因频率比较,差异均无统计学意义(x2 =3.02,0.77;P>0.05).I/D基因型分布:DR组分别为Ⅱ 25.1%,ID 58.0%,DD 16.9%;DWR组分别为Ⅱ 22.0%,ID52.2%,DD 25.9%,PDR组分别为Ⅱ 20.7%,ID 64.2%,DD 15.1%;DR组与DWR组和PDR组的I/D基因型分布差异均无统计学意义(x2 =4.92,3.19;P >0.05).糖尿病组与非糖尿病组之间的I和D等位基因频率及I/D基因型分布差异均无统计学意义(x2 =0.25,4.98;P >0.05).在多因素回归分析模型中,纳入患者确诊糖尿病时的年龄、尿微量白蛋白定量检测结果、胰岛素应用情况,肌酐、糖化血红蛋白、血糖检测结果,ACE抑制剂使用情况等作为变量进行分析,显示I/D位点基因多态性与DR(OR=0.80,95% CI:0.59~ 1.09)和PDR(OR=1.23,95% CI:0.78~1.93)发病无相关性.结论 ACE基因I/D多态性与2型糖尿病患者DR的发病无明显相关性.%Objective To investigate the association between angiotensin converting enzyme (ACE) gene locus rs1799752 insertion/deletion (I/D) polymorphism and diabetic retinopathy

  10. EFFECT OF CURCUMIN LIPOSOMAL FORM ON ANGIOTENSIN CONVERTING ACTIVITY, CYTOKINES AND COGNITIVE CHARACTERISTICS OF THE RATS WITH ALZHEIMER’S DISEASE MODEL

    V. V. SOKOLIK; S. M. SHULGA

    2015-01-01

    The purpose of the study was the investigation of curcumin liposome form effect on angiotensinconverting enzyme activity, cytokines and mnestic features of rats with experimental model of Alzheimer’s disease. In the animals with intrahippocampal injection of А42_Human, nasal therapy with curcumin liposome form was used. Cytokine concentration and angiotensin converting enzyme activity in brain regions (cerebral cortex and hippocampus) and in blood serum as well as indicators of conditioned a...

  11. Misdiagnosis and mistreatment of ace-inhibitor induced cough decreases therapy compliance

    Vegter, S.; de Boer, P.; van Dijk, K. W.; Visser, S. T.; de Jong-van den Berg, L. T.

    2012-01-01

    OBJECTIVES: A common adverse effect of angiotensin-converting enzyme inhibitors (ACEi) is a persistent dry cough. Physicians and pharmacists who fail to recognise dry cough to be ACEi related may prescribe cough suppressants (antitussives), instead of recommended ACEi substitution. The aim of this s

  12. Ace inhibitors and cardiovascular regulation : the importance of autocrine and paracrine mechanisms

    Wijngaarden, Jan van

    1992-01-01

    As demonstrated in a large number of clinical studies, angiotensin converting enzyme (ACE) inhibitors are of great value for the treatment of cardiovascular disorders. Although the clinical merits of these drugs are now well recognized, their mechanism of action is not yet completely understood. The

  13. Does angiotensin (1-7) contribute to the anti-proteinuric effect of ACE-inhibitors

    van der Wouden, Els A; Henning, Robert H; Deelman, Leo E; Roks, Anton J M; Boomsma, Frans; de Zeeuw, Dick

    2005-01-01

    Angiotensin-converting enzyme inhibitors (ACE-I) reduce proteinuria and protect the kidney in proteinuric renal disease. During ACE-I therapy, circulating levels of angiotensin (1-7) [Ang (1-7)] are increased. As cardiac and renal protective effects of Ang (1-7) have been reported, we questioned whe

  14. Positron emitter labeled enzyme inhibitors

    This invention involves a new strategy for imagining and mapping enzyme activity in the living human and animal body using positron emitter-labeled suicide enzyme inactivators or inhibitors which become covalently bound to the enzyme as a result of enzymatic catalysis. Two such suicide inactivators for monoamine oxidase have been labeled with carbon-11 and used to map the enzyme subtypes in the living human and animal body using PET. By using positron emission tomography to image the distribution of radioactivity produced by the body penetrating radiation emitted by carbon-11, a map of functionally active monoamine oxidase activity is obtained. Clorgyline and L-deprenyl are suicide enzyme inhibitors and irreversibly inhibit monoamine oxidase. When these inhibitors are labeled with carbon-11 they provide selective probes for monoamine oxidase localization and reactivity in vivo using positron emission tomography

  15. Nutrition Evaluation of Silkworm Pupal Proteins with Various Solubility and Inhibitory Activity of Their Enzymatic Digested Products to Angiotensin-converting Enzyme%蚕蛹不同溶解性蛋白的营养学评价及酶解物对血管紧张素转换酶的抑制活性

    吴琼英; 徐金玲; 贾俊强; 桂仲争; 谭广秀

    2011-01-01

    分别对缫丝蚕蛹中的水溶性和碱溶性蛋白组分进行营养学评价,为高效开发蚕蛹食品提供依据;通过蚕蛹蛋白酶解产物对血管紧张素转换酶(ACE)的体外抑制活性试验,探讨蚕蛹蛋白作为天然降压药品原料的利用潜力.营养学分析表明:蚕蛹蛋白水溶性和碱溶性组分中的氨基酸种类齐全,且必需氨基酸占总氨基酸的质量分数分别为41.2%和39.2%,明显高于WHO推荐的氨基酸组成模式(>36%);蚕蛹水溶性蛋白有第1~第4限制性氨基酸(依次为亮氨酸、异亮氨酸、缬氨酸和苏氨酸),而蚕蛹碱溶性蛋白仅有第1和第2限制性氧基酸(依次为蛋氨酸+胱氨酸、畀亮氨酸),2种溶解性蛋白的生物效价均较低,在开发利用中,应补充限制性氨基酸或与其它蛋白搭配使用,以提高产品的营养价值.体外ACE抑制活性试验表明,蚕蛹的水溶性蛋白和碱溶性蛋白的碱性蛋白酶酶解产物均具有较强的ACE抑制活性,IC50值分别为0.121、0.113 mg/mL,2种蛋白有可能成为降血压肽生产原料.%In order to provide reference for efficient development of food with silkworm pupae, the water-soluble and alkalisoluble protein fractions from silkworm pupae of reeled cocoons were evaluated on their nutritional quality. Their utilization potential as protein resources for preparing natural blood pressure reducing medicine was investigated through assaying the in vitro inhibition activity of their alcalase hydrolysates to angiotensin-converting enzyme (ACE). Nutrition analysis showed that both water-soluble and alkali-soluble protein fractions had complete composition of amino acids with mass fractions of essential amino acids to total amino acids as high as 41.2% and 39. 2% respectively, being obviously higher over the amino acid composition standard recommended by WHO ( >36% ). Leucine, isoleucine, valine and threonine were the 1 st, 2nd, 3rd and 4th limiting amino acids respectively in water

  16. 鳄鱼血蛋白酶解产物抗氧化特性和血管紧张素转化酶抑制活性研究%Study on the antioxidant properties and angiotensin-converting enzyme inhibitory activity of crocodile blood protein enzymatic hydrolysate

    黄和平; 陈孙福; 罗永康

    2014-01-01

    研究了鳄鱼血蛋白酶解产物的抗氧化特性和对血管紧张素转化酶( ACE)的抑制活性。利用木瓜蛋白酶酶解鳄鱼血浆蛋白和血球蛋白,用分光光度法测定了酶解产物的抗氧化能力和用高效液相色谱( HPLC)测定其ACE的抑制率。结果显示:鳄鱼血浆和血球蛋白酶解产物的亚铁离子螯合能力差异性不显著( P>0.05);在0~5 mg/mL的浓度范围内,血球蛋白酶解产物清除ABTS自由基的能力大于血浆蛋白酶解产物,且在浓度为1 mg/mL时,两者清除ABTS自由基的能力差异性极显著( P<0.01);血浆蛋白酶解产物清除DPPH自由基的能力在0~5 mg/mL的浓度范围内随着蛋白浓度的增加而升高,血球蛋白酶解产物在蛋白浓度为4 mg/mL处达到最大清除率,之后下降;在0~20 mg/mL的浓度范围内,两种酶解产物的还原力随着蛋白浓度的提高显著升高,但两者还原力的差异性不显著( P>0.05);鳄鱼血浆和血球蛋白酶解产物对ACE具有良好的抑制力,其最大抑制率可分别达到75.56%和86.42%。研究表明,鳄鱼血蛋白酶解产物在体外具有抗氧化和抑制ACE的活性。%The antioxidant properties and angiotensin-converting enzyme ( ACE) inhibitory activity of enzymatic hydrolysate from crocodile blood protein were analyzed. The crocodile plasma and blood cell protein were hydrolyzed by papain, and then antioxidant properties and ACE inhibition rate of enzymatic hydrolysate were measured by spectrophotometer and HPLC. Results showed that there were no statistical significance ( P>0.05) between the enzymatic hydrolysate of crocodile plasma and blood cell protein; the ABTS radical-scavenging ability of enzymatic hydrolysate from blood cell protein was higher than that from crocodile plasma protein from 0 to 5 mg/mL of protein concentration, and there were statistical significance at P0.05) between them ; crocodile plasma

  17. A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough

    Mosley, J D; Shaffer, C M; Van Driest, S L;

    2016-01-01

    The most common side effect of angiotensin-converting enzyme inhibitor (ACEi) drugs is cough. We conducted a genome-wide association study (GWAS) of ACEi-induced cough among 7080 subjects of diverse ancestries in the Electronic Medical Records and Genomics (eMERGE) network. Cases were subjects...

  18. Relationship of polymorphism of angiotensin-converting enzyme gene and insulin resistance and blood lipid in Mongolian hypertensives%蒙古族高血压者血管紧张素转换酶基因多态性与胰岛素抵抗及血脂的关系

    刘丽娟; 叶宏; 佟伟军; 刘国玉; 李永山; 黄桂蓉; 王健; 张永红

    2004-01-01

    BACKGROUND: Angiotensin-converting enzyme(ACE) gene is considered one of the candidate genes of hypertension. Moreover, insulin resistance and high blood lipid are considered to be related to hypertension. Because of the genetic heterogeneity, it is necessary to study the association between ACE gene polymorphism and insulin resistance and blood lipid in hypertensives of different nationalities.OBJECTIVE: To investigate the association between insertion/deficiency (I/D) polymorphism of ACE gene and insulin resistance and blood lipid in Mongolian hypertensives.DESIGN: A study of epidemiological prevalence.SETTING: Department of Epidemiology, Public Health College of Harbin Medical University; Department of Epidemiology, Radiation Medicine and Public Health College of Suzhou University; Department of Clinical Laboratory, Center of Prevention and Control of Diseases in Tongliao City; Department of Epidemiology, Public Health Station and Epidemic Prevention of Kezuohouqi.PARTICIPANTS: The present study was conducted with inhabitants lived in Chaolutusumu Country, Kezuohouqi in Tongliao City, Inner Mongolia. Totally 115 hypertensives were selected.INTERVENTIONS: I/D polymorphism of ACE gene was measured by polymerase chain reaction, and blood lipid, blood glucose and insulin were tested with kit.MAIN OUTCOME MEASURES: Blood lipid, blood sugar, insulin and insulin sensitivity index.RESULTS: Among the 115 hypertensives, 33 were with Ⅱ genotype, 62 with ID genotype and 20 with DD genotype. In the three groups, total cholesterol (TC) was(5.1 ± 1.4), (5.2 ±1.5) and(4.9 ± 1.1) mmoL/L respectively;trioleate glyceryl was(3.4±2.5), (3.4±3.0) and(2.9±1. 8) mmoL/L respectively; High density lipoprotein(HDL) was(1.3 ±0. 7), (1.2 ±0. 6)and ( 1.3 ± 0.9) mmoL/L respectively; Low density lipoprotein (LDL) was (3.1 ± 1.4), (3.4 ± 1.4) and(3.0 ± 1.2) mmoL/L respectively. There was no significant difference among groups( P > 0. 05) . Blood glucose was (5.5±1.1), (5.9±2

  19. Genetic variation and gender determine bradykinin type 1 receptor responses in human tissue: Implications for the ACE-inhibitor-induced effects in patients with coronary artery disease

    H. Wu (Haiyan); A.J.M. Roks (Anton); F.P.J. Leijten (Frank); I.M. Garrelds (Ingrid); U. Musterd-Bhaggoe (Usha); A. van den Bogaerdt (Antoon); M.P.M. de Maat (Moniek); M.L. Simoons (Maarten); A.H.J. Danser (Jan); H. Oeseburg (Hisko)

    2014-01-01

    textabstractThe efficacy of the ACE (angiotensin-converting enzyme) inhibitor perindopril in coronary artery disease [EUROPA (European trial on reduction of cardiac events with perindopril in stable coronary artery disease) study] is associated with the rs12050217 A/G single nucleotide polymorphism

  20. 先心病心脏重构患者血清血管紧张素转化酶2水平研究%The Serum Levels of Angiotensin-converting Enzyme2 in Patients of Congenital Heart Disease with Cardiac Remodeling

    郭玥; 吕宁; 尹小龙

    2013-01-01

    目的 观察先心病(congenital heart disease,CHD)伴心脏重构(Cardiac remodeling)患者血管紧张素转化酶2 (angiotensin-convertirg enzyrre 2,ACE2)含量和活性的变化,探讨它们与心脏重构的关系.方法 收集被确诊为先心病的患者104例, (其中无心脏重构组80例,合并心脏重构组24例),正常对照组33例.抽取受试者静脉血,应用酶联免疫吸附法(ELISA)检测血清ACE2酶含量,用比色法检测ACE2酶活性的水平,所得实验数据使用SPSS统计软件进行分析.结果 (1)正常对照组、先心病无心脏重构组、先心病心脏重构组ACE2酶含量测定值分别为(15.79± 5.03) U/L、(18.85±6.46) U/L、(14.80±4.58) U/L.正常对照组与先心病无心脏重构组比较,ACE2含量差异有统计学意义(P<0.05);正常对照组与先心病心脏重构组比较,ACE2含量无差异(P>0.05);先心病无心脏重构组与心脏重构组比较,ACE2含量差异有统计学意义(P<0.01); (2)正常对照组、先心病无心脏重构组、先心病心脏重构组ACE2酶活性测定值分别为(1.75±0.82) U/L、(1.85±0.62) U/L、(158±0.52) U/L,3组间比较差异无统计学意义(P>0.05).结论 (1)先心病无心脏重构患者血清中的ACE2酶含量显著升高; (2)先心病无心脏重构患者与心脏重构患者血清中ACE2酶活性无变化.%Objective To observe the Angiotensin-converting enzyme2 (ACE2) protein contents and activity in the serum of patients with Congenital Heart Disease (CHD) combined with cardiac remodeling (CR) , and investigate the correlation of those with cardiac remodeling. Methods 104 patients with Congenital Heart Disease and 33 normal control patients were collected. The patients with congenital heart disease were divided into 80 cases of non-cardiac remodeling group, and 24 cases of cardiac remodeling group. The serum levels of ACE2 protein were detected by enzyme-linked immunosorbent assay ( ELISA) , ACE2 activity was detected by colorimetric

  1. ANGIOTENSIN-CONVERTING ENZYME GENE POLYMORPHISM IN UNTREATED ESSENTIAL HYPERTENSION AND RESPONSE TO ANGIOTENSIN CONVERTING ENZYME INHIBITORS%血管紧张素转换酶基因多态性与血管紧张素转换酶抑制剂的降压作用

    曹文; 凌树森; 张启高; 陈亚利

    1999-01-01

    目的:从基因多态性研究药效的差异.方法:选择健康志愿者99例,未治疗的原发性高血压病人40例,用PCR方法检测血管紧张素转换酶(ACE)基因的插入与缺失(I/D)多态性, 用血管紧张素转换酶抑制剂(ACEI)卡托普利治疗高血压病人.结果:正常人与原发性高血压患者的ACE等位基因频率及基因型频率无显著差异(P>0.05).卡托普利降压有效病人与无效病人ACE基因的I/D等位基因频率及基因型频率,基因缺失型纯合子(DD)或/和杂合子(ID)与非缺失型(II)也均无显著差异(P>0.05).结论:ACE基因的I/D多态性与原发性高血压的发病无关,ACEI降压作用的个体差异与ACE基因的I/D多态性无关.

  2. 血管紧张素转换酶抑制剂所致咳嗽与血管紧张素转换酶基因多态性的相关性%Relationship Between Polymorphism of Angiotensin Converting Enzyme Gene and Cough Caused by Angiotensin Converting Enzyme Inhibitors

    施美君; 刘丹; 胡克; 陈国忠; 杨炯

    2008-01-01

    目的:探讨原发性高血压患者在口服血管紧张素转换酶抑制剂(ACEI)后发生的咳嗽与血管紧张素转换酶(ACE)基因多态性之间的相关性.方法:应用多聚酶链反应(PCR)对口服ACEI 的原发性高血压患者(包括发生咳嗽与不发生咳嗽者)ACE 基因多态性进行检测,并比较两组患者服药前血清 ACE 水平. 结果:130 例患者中有51例(39.2%) 发生咳嗽.咳嗽组 ACE 的 I 型等位基因及 II 型基因型频率分别为 62.7%和 54.8%,非咳嗽组分别为 39.2% 和 21.5%,两组比较差异有显著性(P<0.05).咳嗽组服药前血清ACE 水平 [(27.37±11.43) U/ L] 明显低于非咳嗽组 [(45.21±12.56)U/ L],两组血清ACE水平比较差异有显著性(P<0.001).服药前血清ACE水平在DD基因型最高 [(36.65±12.78)U/L],ID型次之 [(27.84±7.11)U/ L],II 型最低 [(23.02±8.31)U/L],3 个基因型间比较差异有显著性(P<0.01).结论:血清 ACE 水平及 ACE 基因多态性与高血压患者口服 ACEI 后所致的咳嗽有关.

  3. The relationship between polymorphism of angiotensin converting enzyme gene and cough caused by angiotensin converting enzyme inhibitors%血管紧张素转化酶抑制剂所致咳嗽与血管紧张素转化酶基因型相关性的研究

    杨素敏; 何权瀛; 苗懿德

    2003-01-01

    目的探讨老年原发性高血压患者口服血管紧张素转换酶抑制剂(ACEI )后发生咳嗽的机制. 方法应用聚合酶链反应(PCR),检测老年原发性高血压患者口服ACEI后发生咳嗽与无咳嗽者的血管紧张素转化酶(ACE)基因多态性,检测并比较两组患者血清ACE水平及ACE水平预测高血压患者口服ACEI引起咳嗽的敏感性和特异性. 结果 ACEI所致咳嗽组ACE基因Ⅱ型的频率为40%,显著高于无咳嗽组(20%,P<0.05) ,Ⅰ等位基因频率为60%,显著高于无咳嗽组(41%,P<0.01) .两组患者血清ACE水平在DD型、ID型、Ⅱ型依次减低.咳嗽组血清ACE水平显著低于无咳嗽组(P<0.001),血清ACE水平预测ACEI引起咳嗽的敏感性和特异性分别为81%和78%. 结论老年高血压患者口服ACEI所致咳嗽与血清ACE水平及ACE基因多态性有关.

  4. 老年抑郁症患者血管紧张素转换酶基因多态性与认知功能关系研究%The relationships of the angiotensin converting enzyme gene polymorphism and cognitive function in senile depressive patients

    王小泉; 王祖森; 袁勇贵

    2013-01-01

    目的 探讨老年抑郁症患者血管紧张素转换酶(ACE)基因第16内含子插入/缺失(Insertion/Deletion,I/D)多态性分布特征和认知功能及其之间的关系.方法 采用病例对照研究,病例组为97例符合美国精神障碍诊断统计手册第4版(Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition,DSM-Ⅳ)抑郁症诊断标准的住院患者,其中男性33例,女性64例,年龄60~78岁,平均年龄(68±5)岁;健康对照组103例,其中男性30例,女性73例,平均年龄(66±6)岁.所有的患者及44例健康对照者完成了汉密尔顿抑郁量表(HAMD)评估及神经心理学测试.用聚合酶链式反应(PCR)法进行ACE基因扩增和Ⅰ/D多态性分型.结果 患者组的神经认知测试成绩除连线测试B成绩外,其余的成绩都显著低于正常对照组(P<0.001);相关性分析显示患者组的数字广度测试(顺背)成绩与HAMD总分成负相关(r=-0.213,P=0.040).患者组和对照组间基因型及等位基因频率分布差异无统计学意义(x2=1.745,P=0.418;x2 =0.700,P=0.403);进一步按性别分层分布差异无统计学意义(P>0.05).患者组各基因型间在认知功能方面的差异无统计学意义(P>0.05).结论 老年抑郁症患者存在广泛的认知功能受损,抑郁严重程度与工作记忆成绩密切相关,ACE基因I/D多态性与老年抑郁症的发病及认知功能无显著关联性.%Objective To explore the relationships between angiotensin converting enzyme (ACE) gene polymorphism of insertion/deletion(I/D) and cognition function in senile depressive patients in Chinese Han population.Methods 97 patients with major depression were recruited according to the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition criteria,and 103 healthy persons were used as controls.The Hamilton Depression Scale (HAMD) and neuropsychological tests were used to assess depressive severity and cognitive function in all patients and 44 healthy

  5. Effect of overexpresssion of angiotensin converting enzyme 2 on ventricular remodeling in rats after myocardial infarction%血管紧张素转换酶2过表达对大鼠急性心肌梗死后心室重构的影响及其分子机制

    张全军; 殷跃辉; 吕瑾; 范晋奇; 邹立力; 张波

    2013-01-01

    目的 探讨血管紧张素转换酶2(angiotensin converting enzyme 2,ACE2)过表达对大鼠急性心肌梗死(acute myocardial infarction,AMI)后心室重构的影响及其可能的分子机制.方法 采用开胸结扎冠状动脉法建立SD大鼠AMI模型,将模型大鼠随机分为MI、MI+(NS)、MI+ AdEGFP、MI+ AdACE2组,另设SHAM(假手术)组,每组15只,MI+ NS、MI+ AdEGFP和MI+ AdACE2组沿心肌梗死周边区选取5个点,通过直接心肌内注射方式分别注射NS、AdEGFP和AdACE2,SHAM和MI组不注射.术后4周末,采用Western blot法检测大鼠心肌梗死周边区心肌组织中ACE2、α-SMA、MKP-1、ERK1/2、p-ERK1/2、P38、TGF-β1蛋白的表达;HE染色后于普通显微镜下观察心肌组织结构及细胞炎症变化,天狼猩红-饱和苦味酸染色后于普通显微镜及偏振光显微镜下分别观察心肌胶原表达分布情况;SP免疫组化染色法检测大鼠心肌梗死周边区心肌组织中AngⅡ、Ang(1-7)、α-SMA蛋白的表达,同时采用ELISA法检测Ang(1-7)蛋白的表达;使用羟脯氨酸试剂盒检测大鼠心肌梗死周边区心肌组织中羟脯氨酸含量.结果 术后4周末,MI+ AdACE2组大鼠心肌梗死周边区心肌组织中ACE2蛋白的表达量显著高于其他各组,同时Ang(1-7)蛋白的表达量也显著升高(P<0.05);与SHAM组相比,MI、MI+ NS、MI+ AdEGFP组大鼠心肌梗死周边区心肌组织中AngⅡ、Ang(1-7)、α-SMA蛋白的表达量显著升高(P<0.05),MI+AdACE2组与MI、MI+NS、MI+AdEGFP组相比,AngⅡ、α-SMA蛋白表达水平降低,Ang(1-7)蛋白表达水平升高更显著;与MI、MI+ NS、MI+ AdEGFP各组相比,MI+ AdACE2组大鼠心肌梗死周边区心肌组织中MKP-1蛋白的表达水平明显增加(P<0.05),p-ERK、P38、TGF-β1蛋白的表达水平降低,羟脯氨酸含量显著降低(P<0.05);HE染色和天狼猩红-饱和苦味酸染色证实,ACE2对AMI后梗死周边区的炎症反应和胶原重塑均有明显的改善作用.结论 ACE2在心肌

  6. ACE and platelet aggregation inhibitors from Tamarix hohenackeri Bunge (host plant of Herba Cistanches) growing in Xinjiang

    Xing, Yachao; Liao, Jing; Tang, Yingzhan; Peng ZHANG; Tan, Chengyu; Ni, Hui; Wu, Xueqin; Li, Ning; Jia, Xiaoguang

    2014-01-01

    Background: Tamarix hohenackeri Bunge is a salt cedar that grows widespread in the desert mountains in Xinjiang. T. hohenackeri has not been investigated earlier, although there are many reports of phytochemical work on other Tamarix species. Materials and Methods: To find out natural angiotensin-converting enzyme (ACE) inhibitor and platelet aggregation inhibitors, the bioactive extract (ethyl acetate [EtOAc] fraction) from the dried aerial parts of T. hohenackeri were investigated. The acti...

  7. ACE inhibitors can induce circulating antibodies directed to antigens of the superficial epidermal cells.

    Cozzani, Emanuele; Rosa, Gian Marco; Drosera, Massimo; Intra, Chiara; Barsotti, Antonio; Parodi, Aurora

    2011-07-01

    Drug-induced pemphigus has been reported in patients receiving angiotensin-converting enzyme inhibitors. The aim of this work was to study a group of hypertensive patients without skin diseases treated with angiotensin-converting enzyme (ACE) Inhibitors (I), to verify the presence of serum circulating anti-antibodies. The indirect immunofluorescence showed that 33 sera (52.38%) presented autoantibodies directed to an antigen of the cytoplasm of the superficial epidermal keratinocytes. Two of the 33 positive sera had antibodies to Dsg1 and/or 3 in ELISA. Immunoblot analyses were negative. All the 48 control sera were found to have no circulating antibodies using the three assays. Our results would confirm that ACEI drugs may trigger the production of circulating autoantibodies also in patients without clinical manifestations of pemphigus. PMID:20563876

  8. A Meta-analysis of angitensin-converting enzyme inhibitors on normotensive early diabetic renal diseases

    GENG Li; GU Ming-jun; LIU Zhi-min; FAN Cheng-hui

    2001-01-01

    To make a systematic assessment on whether the progression of early diabetic renal disease with normotension may be slowed down by angiotensin-converting enzyme (ACE) inhibitors. Methods: Randomized clinical experiments published on MEDLINE from January 1990 to April 1999 and on China Biological Medicine were reviewed for studying the effects of ACE-inhibitors on normotensive patients with early diabetic renal diseases. Based on the inclusion criteria, 10 studies were selected. Their results were combined and analyzed with RevMan3.1 software.Results: The pooled effect of urinary microalbumin excretion rate, systolic blood pressure, diastolic blood pressure and mean arterial blood pressure were -77.502 mg/24 h [-100.748 to-54.256], -5.002 mmHg [-9.630 to 0.685], -2.949mmHg [-4.005 to 1.892], -4.284 mmHg [-5.444 to 3.123] respectively. Using clinical albuminuria as the end-point. The pooled odd ratio was 0.27 [95% CI 0.18 0.40]. The sub-group analysis showed that those results had no difference between type 1 and type 2 diabetes. There was no significant correlation between the pooled effects of urinary micro-albuminuria excretion rate and systolic blood pressure, diastolic blood pressure or mean arterial blood pressure. Conclusion:ACE inhibitors can decline urinary micro-albuminuria excretion rate in normotensive patients with early diabetic renal disease and delay the progression of early diabetic renal disease to clinical albuminuria. These effects may not be dependent on its blood pressure-reduction effect.

  9. Purification and characterization of an angiotensin converting enzyme inhibitor from agkistrodon acutus%蕲蛇毒中抑制ACE活性组分的分离纯化与表征

    宴会根

    2000-01-01

    蕲蛇粗毒流经强阴离子交换色谱POROS 20 HQ 柱, 经毛细管电泳仪检测, 5个蛋白峰具有ACE抑制活性, 对最强的活性峰进行PAGE切割电泳的分离, 得到3条带, 经检测只有第三条带(AI-3)具有ACE抑制活性. 该组分的分子量为20 200 (非还原), 加DTT处理后, 分子量为25 900. 其IC50为0.10 mmol/L.

  10. Effect of Captopril, An Angiotensin-Converting Enzyme Inhibitor, on Experimental Pulmonary Fibrosis%卡托普利对实验性肺间质纤维化的干预作用

    夏蕾; 徐启勇; 叶燕青

    2003-01-01

    目的:观察血管紧张素转换酶(ACE)活性在博莱霉素(BLM)所致大鼠肺间质纤维化过程中的动态变化,了解ACE抑制剂卡托普利(CPT)对大鼠肺纤维化模型的影响.方法:45只SD大鼠随机分为3组:对照组、模型组和用药组.模型组和用药组经气管内注入BLM诱导肺纤维化,随即分别每日胃管内灌注生理盐水和CPT(60 mg*kg-1*d-1)进行干预;对照组气管和胃管内灌注均以生理盐水代替.各组动物均于气管内灌药后7,14,28 d 分别处死5只,测动物体重及肺湿重,取肺组织做HE染色,Ⅰ、Ⅲ型胶原的免疫组化,并行图像分析;心腔内取血测ACE的活性.结果:血清ACE活性在气管内灌注BLM后迅速上升,第7 d 达到高峰(与对照组比P<0.01),随后下降,到第28 d 基本恢复正常.CPT能显著降低血清中ACE的活性,减少肺内胶原的表达,减轻肺泡炎和肺纤维化的程度.结论:CPT能减轻BLM诱导的大鼠肺泡炎和肺纤维化.

  11. Pharmacological mechanism and clinic application of angiotensin-converting enzyme inhibitor%血管紧张素转换酶抑制剂的药理机制及其临床应用

    黄文奕

    2005-01-01

    目的:对血管紧张素转换酶抑制剂(ACEI)从药物结构与特征、药动学、药理机制及临床应用等几个方面进行评价,为临床合理使用此类药物提供参考资料.方法:收集并查阅各种与ACEI有关的国内外文献进行归纳总结.结果:ACEI主要通过与血管紧张素转换酶(ACE)结合来抑制ACE的活性,从而降低血管紧张素Ⅱ(AⅡ)的合成,减少其对靶血管的作用;ACEI应用广泛,现已大量应用于高血压、动脉粥样硬化、慢性心力衰竭、慢性肾功能不全等疾病的治疗.结论:ACEI是一类性能优异的药物,正确合理的使用是临床科学用药的关键.

  12. 血管紧张素转换酶抑制剂特性及其分类比较%THE CHARACTER AND COMPARISON OF ANGIOTENSIN CONVERTING ENZYME INHIBITORS

    曾惠琴; 周存山; 金辉

    2006-01-01

    讨论了ACE酶在血压调节中的生理意义,ACEI的不良反应和ACEIP的特点,不同食物蛋白来源的ACEIP,及这些肽在开发防治高血压的新型功能型食品方面的应用前景.

  13. 两种血管紧张素转换酶抑制剂对冠状动脉侧支循环的影响%Effect of different angiotensin converting enzyme inhibitors on coronary collateral circulation

    张兴华; 马晓静; 罗集; 邵建华; 耿庆信; 朱兴雷; 唐元升; 许法运

    2004-01-01

    目的建立狗急性心肌缺血模型,观察不同血管紧张素转换酶抑制剂(ACEI)对血管紧张素转换酶(ACE)活性、冠状动脉侧支循环形成的影响.方法选健康杂种犬24条随机分为卡托普利组、苯那普利组、对照组.结扎前降支近端,测量冠状动脉舒张压(DCP)、侧支返流量(Qret)及主动脉舒张压(DAP).术后给予不同药物干预,采血测定血浆ACE活性.第2次手术后,将狗处死,提取标本,观察冠状动脉侧支循环形成情况以及组织ACE活性.结果 (1)卡托普利、苯那普利组用药前、用药后10 d及用药后25 d血浆ACE活性分别为(57.6±0.8) U/L、(24.1±0.6) U/L、(24.3±0.6) U/L及(59.5±1.3) U/L 、(24.4±0.4) U/L、(24.0±0.5) U/L,用药后两组血浆ACE活性均明显降低(P<0.01),但两组间差异无显著意义.对照组、卡托普利组、苯那普利组心脏组织ACE活性分别为 (13.0±2.9) U·L-1·g-1、(7. 9±1.6) U·L-1·g-1及(1.83±0.74) U·L-1·g-1.卡托普利、苯那普利组ACE活性均明显低于对照组(P<0.01),而苯那普利组ACE活性明显低于卡托普利组(P<0.01).(2)对照组、卡托普利组用药后DCP明显升高[(3.45±0.63) kPa及(3.42±0.59) kPa,P<0.05].苯那普利组用药后DCP与用药前比较有降低趋势,但差异无显著意义.(3)3组用药后侧支循环血流量(Qcol)均明显增加,分别为(2.01±0.31) ml/min、(2.24±0.46) ml/min及(3.18±0.27) ml/min,P<0.05,苯那普利组Qcol明显高于卡托普利组和对照组(P<0.05).(4)苯那普利组、卡托普利组、对照组缺血区心肌微血管密度分别为(3656±178)条/mm2、(2819±175)条/mm2、(2740±185)条/mm2,高于非缺血区(P<0.01), 苯那普利组明显高于卡托普利组、对照组(P<0.01),卡托普利组、对照组间差异无显著意义.结论苯那普利能促进缺血区冠状动脉侧支循环的建立,改善缺血区的血液供应,而卡托普利无此作用.

  14. Use of Ophiocordyceps sinensis (syn. Cordyceps sinensis) combined with angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) versus ACEI/ARB alone in the treatment of diabetic kidney disease: a meta-analysis.

    Luo, Ying; Yang, Shi-kun; Zhou, Xun; Wang, Ming; Tang, Dan; Liu, Fu-you; Sun, Lin; Xiao, Li

    2015-05-01

    Ophiocordyceps sinensis (O. sinensis; syn. Cordyceps sinensis) has been used in clinical therapy for diabetic kidney disease (DKD) for more than 15 years. O. sinensis is a household name in china and it is available even in supermarket. However, the precise role of O. sinensis has not been fully elucidated with meta-analysis. The aim of this study was to review existing evidence on the effectiveness of O. sinensis for the treatment of DKD. We identified 60 trials involving 4288 participants. Overall, O. sinensis combined with ACEI/ARB had a better effect when compared to ACEI/ARB alone on 24 h UP (MD = -0.23 g/d, 95% CI: - 0.28 to -0.19, p sinensis combined with ACEI/ARB may have a more beneficial effect on the proteinuria, inflammatory, dyslipidemia status as compared to ACEI/ARB alone in DKD III-IV stage patients, while there is no evidence that O. sinensis could improve the hyperglycemia status. However, with regard to low-quality and significant heterogeneity of included trials, to further verify the current results from this meta-analysis, long-term and well-designed RCTs with high-quality study are warranted to ascertain the long-term efficacy of O. sinensis. PMID:25682973

  15. 高血压患者用血管紧张素转换酶抑制剂治疗时的骨密度%Bone mineral density in hypertensive patients under treatment with angiotensin-converting enzyme inhibitor

    阎德文; 王建平; 吴清平; 王月菊

    1999-01-01

    目的探讨血管紧张素转换酶抑制剂(ACEI)对人体中轴骨骨量的影响.方法我们将128例绝经后妇女分为4组:A组:正常血压组46例;B组:高血压ACEI短程(<5年,中位数为3年)治疗组18例;C组:高血压ACEI长程(≥5年,中位数7.5年)治疗组30例;D组:高血压心痛定治疗组34例.采用双能X线吸收法测量其腰椎正侧位(APL2-4、LatL2-4)和左股骨近端各区(包括Neck、Troch、Inter、Total和Wards)的骨密度,并检测了部分患者血清BGP和晨尿羟脯氨酸(Hop/Cr)等生化指标.结果 B组和C组APL2-4骨密度分别明显高于D组;B组和C组股骨近端除Troch外其他各区骨密度均分别明显高于D组,且C组尚显著高于A组,有显著差异(P<0.05);同A组和D组相比,B组和C组Troch和LatL2-4骨密度亦有增加趋势.此外,C组骨密度比B组有增高趋势,但差异无显著意义.B组和C组血清BGP和晨尿HOP水平分别明显低于A组或D组(P<0.05),但B、C二组间无显著差异;各组间血清钙、磷、ALP水平无显著差异.结论 ACEI对骨量具有一定的保持作用,特别适用于老年女性高血压患者.

  16. Protection of Angiotensin converting enzyme Inhibitor and receptor antagonist in cardiovascular system%血管紧张素转换酶抑制剂及受体拮抗剂的心血管系统保护作用

    黄元伟

    2002-01-01

    @@ 1血管紧张素转换酶抑制剂(ACEI)作用广泛,主要用于心血管疾病的防治 目前在我国上市的已有卡托普利(Captopril)、依那普利(enalapril)、西拉普利(Cilazapril)、培哚普利(Perindopril)、赖诺普利(Lisinopril)、苯那普利(benazepril)、福辛普利(Fosinopril)、雷米普利(rimipri).

  17. The effect of esmolol on corrected-QT interval, corrected-QT interval dispersion changes seen during anesthesia induction in hypertensive patients taking an angiotensin-converting enzyme inhibitor

    Zahit Çeker; Suna Akin Takmaz; Bülent Baltaci; Hülya Basar

    2015-01-01

    BACKGROUND AND OBJECTIVES: The importance of minimizing the exaggerated sympatho-adrenergic responses and QT interval and QT interval dispersion changes that may develop due to laryngoscopy and tracheal intubation during anesthesia induction in the hypertensive patients is clear. Esmolol decreases the hemodynamic response to laryngoscopy and intubation. However, the effect of esmolol in decreasing the prol...

  18. Inhibitors of alanine racemase enzyme: a review.

    Azam, Mohammed Afzal; Jayaram, Unni

    2016-08-01

    Alanine racemase is a fold type III PLP-dependent amino acid racemase enzyme catalysing the conversion of l-alanine to d-alanine utilised by bacterial cell wall for peptidoglycan synthesis. As there are no known homologs in humans, it is considered as an excellent antibacterial drug target. The standard inhibitors of this enzyme include O-carbamyl-d-serine, d-cycloserine, chlorovinyl glycine, alaphosphin, etc. d-Cycloserine is indicated for pulmonary and extra pulmonary tuberculosis but therapeutic use of drug is limited due to its severe toxic effects. Toxic effects due to off-target affinities of cycloserine and other substrate analogs have prompted new research efforts to identify alanine racemase inhibitors that are not substrate analogs. In this review, an updated status of known inhibitors of alanine racemase enzyme has been provided which will serve as a rich source of structural information and will be helpful in generating selective and potent inhibitor of alanine racemase. PMID:26024289

  19. Differential associations between actual and expected GP practice prescribing rates for statins, ACE inhibitors, and beta-blockers: a cross-sectional study in England

    Ward, Paul R; Noyce, Peter R; St Leger, Antony S

    2005-01-01

    Aim To explore the relationship between actual and expected general medical practitioner (GP) practice prescribing rates for statins, angiotensin converting enzyme (ACE) inhibitors, and beta-blockers. Background There is a growing body of literature highlighting inequities in GP practice prescribing rates for many drug therapies. The equity of prescribing is of central importance in the area of therapeutics since it explores the interface between those patients who should and those who actual...

  20. Direct renin inhibition in addition to or as an alternative to angiotensin converting enzyme inhibition in patients with chronic systolic heart failure: rationale and design of the Aliskiren Trial to Minimize OutcomeS in Patients with HEart failuRE (ATMOSPHERE) study

    Krum, Henry; Massie, Barry; Abraham, William T;

    2011-01-01

    AIMS: The renin-angiotensin-aldosterone system (RAAS) represents a key therapeutic target in heart failure (HF) management. However, conventional agents that block this system induce a reflex increase in plasma renin activity (PRA), which may lead to RAAS 'escape'. Direct renin inhibitors (DRIs......) have been developed that decrease PRA and thus may provide a greater RAAS blockade. Aliskiren is the first orally active DRI. Plasma levels of B-type natriuretic peptide (BNP) have been observed to be reduced with aliskiren compared with placebo. The aim of the Aliskiren Trial of Minimizing Outcome...... plasma levels of BNP. Methods Patients tolerant to at least 10 mg or equivalent of enalapril will undergo an open-label run-in period where they receive enalapril then aliskiren. Approximately 7000 patients tolerating this run-in period will then be randomized 1:1:1 to aliskiren monotherapy, enalapril...

  1. 长期服用苯那普利的高血压患者左室肥厚逆转与血管紧张素转换酶基因和Chymase基因多态性的相关性研究%Association between angiotensin converting enzyme gene, chymase gene and regression of left ventricular hypertrophy in patients treated with angiotensin converting enzyme inhibitors

    和红; 李立明; 曹卫华; 刘美贞; 孙宁玲; 吕筠; 胡永华

    2004-01-01

    目的探讨长期服用苯那普利的原发性高血压患者左室肥厚逆转与血管紧张素转换酶(ACE)基因插入/缺失(I/D)多态性和Chymase(CMA)基因A/B多态性的关系.方法收集157例原发性高血压伴左室肥厚患者24个月的随访资料;应用聚合酶链反应和限制性片段长度多态性方法检测ACE基因I/D多态性以及CMA基因A/B多态性;超声心动测量左室舒张末期内径(LVDd)、舒张期室间隔厚度(IVST)及左室后壁厚度(LVPWT).结果 (1)治疗后血压明显下降而心率改变不明显;(2)能明显逆转LVH;(3)ACE基因型间除左室质量(LVM)下降值及左室质量指数(LVMI)下降值在DD基因型明显大于II型和ID型以外,其余各临床指标下降值在ACE基因型间的差异均无统计学意义;(4)CMA基因型间各临床指标下降值的差异均无统计学意义;(5)ACE基因中各基因型与CMA基因中各基因型间不存在交互作用;(6)多元线性逐步回归分析表明,仅ACE基因型与LVMI下降值有关.结论长期服用苯那普利可以明显降低血压、逆转LVH;其中ACE基因为DD型的患者较其他基因型患者更易于LVH逆转,而CMA基因多态性与LVH逆转不相关;两种基因间不存在交互作用.

  2. Relationship of gene polymorphisms of angiotensin convertion enzyme, aldosterone synthase and α-adducin with subclinical renal lesion%血管紧张素转换酶醛固酮合酶α-内收蛋白基因多态性与肾损害的关系

    陈慧; 林慧中; 陈燕; 骆杰伟; 吴小盈; 李德育; 伍延安; 沈晓丽

    2008-01-01

    Objective To investigate the relationship of gene polymorphisms of angiotensin eonvertion enzyme (ACE), aldosterone synthase (CYP11B2)and α-adducin with subclinical renal lesion. Methods I/D polymorphism of ACE gene, -344T/C polymorphism of CYP11B2 gene and 460G/T polymorphism of α-adduein gene were detected by polymerase chain reaction (PCR) and restrictive fragment length polymorphism(RFLP) in 604 normotensive subjects and 1081 primary hypertensive patients whose creatinine (Cr) were less than 2mg/L. The primary hypertensive and normotensive subjects were divided respectively into normal group (Ccr≥60ml/min) and subclinical renal lesion (Ccr<60 ml/min) group, according to creatinine clearance rate (Ccr) calculated by Cockcroft-Gault equation. Results ANOVA, contingency X2 and partition of chi-square were selected. The frequencies of different genotypes of ACE, CYP11B2, and α-adducin were in agreement with Hardy-Weinberg equilibrium in our study. Normal renal function group (A group, n=512) and subclinical renal lesion group (B group, n=92) in normotensive subjects, and normal renal function group (C group, n=828) and subclinical renal lesion group (D group, n=252) in hypertensive patients were compared. The patients in B and D groups were older than those in A and C groups (P0.05).ACE-DD基因型分布频率在高血压肾损害组最高为22.6%(57/252),α-adducin-TT基因型分布频率在血压肾功能正常组最低为13.3%(68/512),分别与其他3组比较,差异有统计学意义(均为P0.05).CYP11B2各基因型的分布频率4组比较,差异无统计学意义(均为P>0.05). 结论 随增龄,肾功能异常增加,ACE-DD基因型与高血压肾损害相关,α-adducin-TT基因型与高血压和肾损害均相关,但未发现CYP11B2基因多态性与肾损害的关系.

  3. Autonomic dysregulation in ob/ob mice is improved by inhibition of angiotensin-converting enzyme

    Hilzendeger, A.M.; da Costa Goncalves, A.C.; Plehm, R.; Diedrich, A.; Gross, V; J.B. Pesquero; Bader, M

    2010-01-01

    The leptin-deficient ob/ob mice are insulin resistant and obese. However, the control of blood pressure in this model is not well defined. The goal of this study was to evaluate the role of leptin and of the renin-angiotensin system in the cardiovascular abnormalities observed in obesity using a model lacking leptin. To this purpose, we measured blood pressure in ob/ob and control animals by radiotelemetry combined with fast Fourier transformation before and after both leptin and enalapril tr...

  4. Angiotensin-converting enzyme inhibition increases glucose-induced insulin secretion in response to acute restraint.

    Schweizer, Júnia R O L; Miranda, Paulo A C; Fóscolo, Rodrigo B; Lemos, Joao P M; Paula, Luciano F; Silveira, Warley C; Santos, Robson A S; Pinheiro, Sérgio V B; Coimbra, Candido C; Ribeiro-Oliveira, Antônio

    2012-12-01

    There is increasing evidence suggesting involvement of the renin-angiotensin system (RAS) in carbohydrate metabolism and its response to stress. Thus, the aim of the present study was to evaluate the effects of chronic inhibition of the RAS on glucose and insulin levels during acute restraint stress. Male Holtzman rats were treated with 10 mg/kg per day enalapril solution or vehicle for 14 days. After 14 days, rats were divided into three experimental groups: enalapril + restraint (ER), vehicle + restraint (VR) and enalapril + saline (ES). Rats in the restraint groups were subjected to 30 min restraint stress, whereas rats in the ES groups were given saline infusion instead. Blood samples were collected at baseline and after 5, 10, 20 and 30 min restraint stress or saline infusion. After restraint, a hyperglycaemic response was observed in the ER and VR groups that peaked at 20 and 10 min, respectively (P inhibition with enalapril may increase glucose-induced insulin secretion in response to acute restraint. PMID:23734984

  5. Serum angiotensin converting enzyme activity and serum copper levels in covert silicosis

    Tiwari R

    2005-01-01

    Full Text Available The present case report describes asymptomatic worker working in quartz crushing unit and having crepitations on ausculation in the middle zone of right lung, diagnosed as grade 1/1 silicotic according to ILO Classification of Pneumoconiosis. The patient had elevated levels of SACE and serum Copper. This is the first time that SACE and serum copper levels were measured in a covert case of silicosis particularly in India.

  6. Serum Levels of Copper, Ceruloplasmin and Angiotensin Converting Enzyme among Silicotic and Non-Silicotic Workers

    Safia Beshir

    2015-06-01

    CONCLUSION: Since respirable dust exposure-linked lung fibrosis disease is non-curable, the biochemical parameters (Cu, ACE and Cp can be used as exposure biomarkers to silica dust, providing a better way for early diagnosis of this deadly disease. Down regulating the inflammatory responses could potentially reduce the adverse clinical pulmonary effects of air pollution.

  7. Radiolabeled enzyme inhibitors as pancreatic scanning agents

    Radiolabeled inhibitors of the pancreatic protease enzymes trypsin and chymotrypsin: I-125-soybean inhibitor (SBI), I-125-human antitrypsin (HAT), and 3H-diisopropylfluorophosphate (DFP) were studied in rats for their uptake in the pancreas. The protease enzyme inhibitor, SBI, was found to retain its enzymatic activity after radio-iodine labeling by iodine-monochloride method. Assay of tissues radioactivity at 5, 15, 30, 60 min and 24 hr after iv injection in rats showed pancreas:liver (P:L) ratios of < 1.4 and pancreas:blood (P:B) ratios of < 1 at all time intervals for each compound. However, ip injection of I-125 SBI showed preferential uptake in pancreas, P:L mean ratios [anti x (range)] of 6.0 (5.5 to 6.3) and P:B mean ratios of [anti x (range)] 2.60 (1.8 to 3.4), up to 60 minutes. These ratios resemble those of Se-75-selenomethionine except that kidney values are higher. Our data suggest that radiolabeled proteins can also show similar good early pancreatic uptake when given ip by escaping immediate liver metabolism. Proteins can readily be tagged with desirable gamma-emitting radionuclides (viz. I-131, I-123, Tc-99m) compared to amino acids and may potentially be suitable for imaging the pancreas. It may be important to study both iv and ip routes of administration in evaluating the specificity/affinity of potential pancreatic radiopharmaceuticals

  8. The Synthetic Strategy toward of ACE-Inhibitors

    CHANG; ChingYao

    2001-01-01

    Angiotensin II is an important octapeptide which is responsible for the increase in blood pressure in three major mechanisms. It acts as a hormone to attack the receptor on the blood vessels, which cause strong vasoconstriction. It is also the major stimulus for release another hormone, aldolsterone, which promote the excretion of potassium ion and retention of sodium and waster. Both of the above effects increase the blood pressure. On the other hand, ACE (Angiotensin Converting Enzyme) catalyzes the hydrolysis of bradykinin that is a potent vasodilator. Therefore, the inhibitor of ACE can act as an efficient anti-hypertensive agent through multiple routes.  ……

  9. The Synthetic Strategy toward of ACE-Inhibitors

    2001-01-01

    @@ Angiotensin II is an important octapeptide which is responsible for the increase in blood pressure in three major mechanisms. It acts as a hormone to attack the receptor on the blood vessels, which cause strong vasoconstriction. It is also the major stimulus for release another hormone, aldolsterone, which promote the excretion of potassium ion and retention of sodium and waster. Both of the above effects increase the blood pressure. On the other hand, ACE (Angiotensin Converting Enzyme) catalyzes the hydrolysis of bradykinin that is a potent vasodilator. Therefore, the inhibitor of ACE can act as an efficient anti-hypertensive agent through multiple routes.

  10. Angiotensin-I-converting enzyme and gallium scan in noninvasive evaluation of sarcoidosis

    Nosal, A. (Harbor General Hospital, Torrance, CA); Schleissner, L.A.; Mishkin, F.S.; Lieberman, J.

    1979-03-01

    Angiotensin-converting enzyme assays and gallium-scan results were obtained from 27 patients with biopsy-proven, clinically active sarcoidosis. Twenty-three of these patients had elevated converting enzyme levels, and 22 had positive gallium-scan results. Three of four patients with normal or borderline-elevated levels of angiotensin-converting enzyme also had positive gallium-scan results. Of 156 nonsarcoid patients (pulmonary and other diseases), 27 were found to have elevated serum converting enzyme levels, and 25 of these had negative gallium-scan results. These results indicate that the combination of an assay of angiotensin-converting enzyme and gallium scan increases diagnostic specificity from 83% to 99% without sacrificing sensitivity. It was concluded that the concurrent use of angiotensin-converting enzyme assay and gallium scan is of value in the diagnosis of sarcoidosis.

  11. Angiotensin-I-converting enzyme and gallium scan in noninvasive evaluation of sarcoidosis

    Angiotensin-converting enzyme assays and gallium-scan results were obtained from 27 patients with biopsy-proven, clinically active sarcoidosis. Twenty-three of these patients had elevated converting enzyme levels, and 22 had positive gallium-scan results. Three of four patients with normal or borderline-elevated levels of angiotensin-converting enzyme also had positive gallium-scan results. Of 156 nonsarcoid patients (pulmonary and other diseases), 27 were found to have elevated serum converting enzyme levels, and 25 of these had negative gallium-scan results. These results indicate that the combination of an assay of angiotensin-converting enzyme and gallium scan increases diagnostic specificity from 83% to 99% without sacrificing sensitivity. It was concluded that the concurrent use of angiotensin-converting enzyme assay and gallium scan is of value in the diagnosis of sarcoidosis

  12. Effect of ACE inhibitor trandolapril on life expectancy of patients with reduced left-ventricular function after acute myocardial infarction. TRACE Study Group. Trandolapril Cardiac Evaluation

    Torp-Pedersen, C; Køber, L

    1999-01-01

    BACKGROUND: The survival benefit from the use of inhibitors of angiotensin-converting enzyme (ACE) in patients with acute myocardial infarction is usually presented in terms of risk ratios and lives saved per 1000 people treated. A more relevant way to present the extent of benefit would......-blind treatment; continued use of trandolapril was recommended at study closure. INTERPRETATION: In patients with severely reduced left-ventricular function, long-term treatment with an ACE inhibitor during the critical period after myocardial infarction is associated with a substantial increase in life...

  13. Benazepril and Hydrochlorothiazide

    ... a class of medications called angiotensin-converting enzyme (ACE) inhibitors. It works by decreasing certain chemicals that tighten ... Lotensin); hydrochlorothiazide (HCTZ, Microzide, Oretic); angiotensin-converting enzyme (ACE) inhibitors such as captopril (Capoten), enalapril (Vasotec, in Vaseretic), ...

  14. Captopril and Hydrochlorothiazide

    ... a class of medications called angiotensin-converting enzyme (ACE) inhibitors. It works by decreasing certain chemicals that tighten ... Capoten); hydrochlorothiazide (HCTZ; Microzide, Oretic); angiotensin-converting enzyme (ACE) inhibitors such as benazepril (Lotensin, in Lotrel), enalapril (Vasotec, ...

  15. Perindopril

    ... a class of medications called angiotensin-converting enzyme (ACE) inhibitors. It makes blood flow more smoothly by preventing ... you are allergic to perindopril, angiotensin-converting enzyme (ACE) inhibitors such as benazepril (Lotensin, in Lotrel), captopril (Capoten), ...

  16. Enalapril and Hydrochlorothiazide

    ... a class of medications called angiotensin-converting enzyme (ACE) inhibitors. It works by decreasing certain chemicals that tighten ... Vaseretic); hydrochlorothiazide (HCTZ, Microzide, Oretic); angiotensin-converting enzyme (ACE) inhibitors such as benazepril (Lotensin, in Lotrel), captopril (Capoten), ...

  17. Cough Syncope due to ACE Inhibitor

    Filiz Koc

    2015-09-01

    Full Text Available Syncope is defined as a transient loss of consciousness due to sudden temporary decline in cerebral perfusion. Cough syncope is classically seen in middle aged obese men with obstructive pulmonary disease. In patients that use Angiotensin converting enzyme (ACE inhibitors, a dry persistent cough can emerge due to the side effects of this medication. Seventy years old male patient that use ACE inhibitor for hypertension accepted to the clinic with the complaint of syncope. A bout of coughing has developed during electroencephalography recording and 10 seconds in duration of subcortical like epileptiform discharges were viewed. The ACE inhibitor the patient was receiving was replaced with calcium channel blocker and no complaint was observed during the follow up period. [Cukurova Med J 2015; 40(3.000: 619-622

  18. Essential fatty acids and their metabolites could function as endogenous HMG-CoA reductase and ACE enzyme inhibitors, anti-arrhythmic, anti-hypertensive, anti-atherosclerotic, anti-inflammatory, cytoprotective, and cardioprotective molecules

    Das Undurti N

    2008-10-01

    Full Text Available Abstract Lowering plasma low density lipoprotein-cholesterol (LDL-C, blood pressure, homocysteine, and preventing platelet aggregation using a combination of a statin, three blood pressure lowering drugs such as a thiazide, a β blocker, and an angiotensin converting enzyme (ACE inhibitor each at half standard dose; folic acid; and aspirin-called as polypill- was estimated to reduce cardiovascular events by ~80%. Essential fatty acids (EFAs and their long-chain metabolites: γ-linolenic acid (GLA, dihomo-GLA (DGLA, arachidonic acid, eicosapentaenoic acid (EPA, and docosahexaenoic acid (DHA and other products such as prostaglandins E1 (PGE1, prostacyclin (PGI2, PGI3, lipoxins (LXs, resolvins, protectins including neuroprotectin D1 (NPD1 prevent platelet aggregation, lower blood pressure, have anti-arrhythmic action, reduce LDL-C, ameliorate the adverse actions of homocysteine, show anti-inflammatory actions, activate telomerase, and have cytoprotective properties. Thus, EFAs and their metabolites show all the classic actions expected of the "polypill". Unlike the proposed "polypill", EFAs are endogenous molecules present in almost all tissues, have no significant or few side effects, can be taken orally for long periods of time even by pregnant women, lactating mothers, and infants, children, and adults; and have been known to reduce the incidence cardiovascular diseases including stroke. In addition, various EFAs and their long-chain metabolites not only enhance nitric oxide generation but also react with nitric oxide to yield their respective nitroalkene derivatives that produce vascular relaxation, inhibit neutrophil degranulation and superoxide formation, inhibit platelet activation, and possess PPAR-γ ligand activity and release NO, thus prevent platelet aggregation, thrombus formation, atherosclerosis, and cardiovascular diseases. Based on these evidences, I propose that a rational combination of ω-3 and ω-6 fatty acids and the co

  19. Angioedema Due to use of ACE-Inhibitor

    Hulya Eyigor

    2014-03-01

    Full Text Available       Angioedema; which may be hereditary or non-hereditary, is defined as a sudden, severe, often in awkward, temporary swelling of skin, subcutaneous and mucous membranes of the face, tongue, lip, larynx, and gastrointestinal areas. Angiotensin Converting Enzyme (ACE inhibitor drugs are widely used in essential hypertension and congestive heart diseases and effective and safe drugs. Angioedema is quite rare due to the use of ACE inhibitors, the rate changes from 0.1 to 0.7% reported in the literature. The pathophysiology of angioedema induced by ACE inhibitors are not completely understood, this situation has been tought to be associated with an increased activity of bradykinin related vasodilatation, increased vascular permeability and interstitial edema. In this study, a case of 65-year-old male patient presented angioedema induced by lisinopril was presented and a very rare side effect of ACE inhibitor drugs was reviewed with the relevant literature.

  20. Procedure to Determine Enzyme Inhibitors Activity in Cereal Seeds

    Fernanda Arnhold Pagnussatt; Silvia Letícia Rivero Meza; Jaqueline Garda-Buffon; Eliana Badiale-Furlong

    2012-01-01

    This work established a procedure for commercial fungal amylase usage as indicator of enzyme inhibitors presence in cereals, intending to screening antifungal resistance properties in cereals. Firstly, the inhibitive effects of oat, wheat and rice protein extracts were assessed against different amylase sources. It was found that the fungal amylase (Fungamyl®) was the most affected by the inhibition property of the extracts. The best conditions for inhibitor-extract-enzyme interaction were es...

  1. The effect of chemical anti-inhibitors on fibrinolytic enzymes and inhibitors

    Sidelmann, Johannes Jakobsen; Jespersen, J; Kluft, C;

    1997-01-01

    proteases. We studied the influence of chemical anti-inhibitors (chloramine T, flufenamate, sodium lauryl sulfate, and methylamine) on fibrinolytic serine proteases and fibrinolytic enzyme inhibitors using the physiological substrate fibrin as plasmin substrate. Low concentrations of chloramine T (0.01 mmol...... plasminogen activators (apparent recovery > 200%). Sodium lauryl sulfate eliminates the major fibrinolytic enzyme inhibitors, but increases the activity of plasmin (apparent recovery > 200%) and plasminogen activator, urokinase type (apparent recovery 130%). Methylamine affects only plasmin inhibition. We...

  2. ACE INHIBITORS: A COMPREHENSIVE REVIEW

    Pradeep Kumar Arora* and Ashish Chauhan

    2013-02-01

    Full Text Available Hypertension is a chronic increase in blood pressure, characterized as primary and secondary hypertension. The disorder is associated with various risk factors like obesity, diabetes, age, lack of exercise etc. Hypertension is being treated since ancient times by Ayurvedic, Chinese and Unani medicine. Now various allopathic drugs are available which include diuretics, calcium channel blockers, α-blockers, β-blockers, vasodilators, central sympatholytics and ACE-inhibitors. Non-pharmacological treatments include weight reduction, dietary sodium reduction, increased potassium intake and reduction in alcohol consumption. ACE-inhibitors are widely used in the treatment of hypertension by inhibiting the angiotensin converting enzyme responsible for the conversion of angiotensin I to angiotensin II (responsible for vasoconstriction. Various structure activity relationship studies led to the synthesis of ACE-inhibitors, some are under clinical development. This comprehensive review gives various guidelines on classification of hypertension, hypertension therapy including ancient, pharmacological, non-pharmacological therapies, pharmacoeconomics, historical perspectives of ACE, renin, renin angiotensin system (circulating vs local RAS, mechanism of ACE inhibitors, and development of ACE inhibitors. Review also emphasizes on the recent advancements on ACE inhibitors including drugs in clinical trials, computational studies on ACE-inhibitors, peptidomimetics, dual, natural, multi-functional ACE inhibitors, and conformational requirements for ACE-inhibitors.

  3. Ace Inhibitors and Angioedema

    Vleeming W; van Amsterdam JGC; de Wildt DJ; Stricker B; TOX

    1995-01-01

    Dit rapport beschrijft de risico's die verbonden zijn aan het gebruik van angiotensine converting enzym (ACE) remmers. Hierbij staat de bijwerking angio-oedeem centraal. De benodigde literatuur is verzameld aan de hand van een zoekaktie middels MEDLINE. ACE-remmers zijn in gebruik ter behand

  4. Analysis of slow-binding enzyme inhibitors at elevated enzyme concentrations.

    Perdicakis, Basil; Montgomery, Heather J; Guillemette, J Guy; Jervis, Eric

    2005-02-15

    The improvement in the characterization of slow-binding inhibitors achieved by performing experiments at elevated enzyme concentrations is presented. In particular, the characterization of slow-binding inhibitors conforming to a two-step mode of inhibition with a steady-state dissociation constant that is much lower than the initial dissociation constant with enzyme is discussed. For these systems, inhibition is rapid and low steady-state product concentrations are produced at saturating inhibitor concentrations. By working at elevated enzyme concentrations, improved signal-to-noise ratios are achieved and data may be collected at saturating inhibitor levels. Numerical simulations confirmed that improved parameter estimates are obtained and useful data to discern the mechanism of slow-binding inhibition are produced by working at elevated enzyme concentrations. The saturation kinetics that were unobservable in two previous studies of an enzyme inhibitor system were measured by performing experiments at an elevated enzyme concentration. These results indicate that consideration of the quality of the data acquired using a particular assay is an important factor when selecting the enzyme concentration at which to perform experiments used to characterize the class of enzyme inhibitors examined herein. PMID:15691501

  5. Biosensors for the determination of environmental inhibitors of enzymes

    Characteristic features of functioning and practical application of enzyme-based biosensors for the determination of environmental pollutants as enzyme inhibitors are considered with special emphasis on the influence of the methods used for the measurement of the rates of enzymic reactions, of enzyme immobilisation procedure and of the composition of the reaction medium on the analytical characteristics of inhibitor assays. The published data on the development of biosensors for detecting pesticides and heavy metals are surveyed. Special attention is given to the use of cholinesterase-based biosensors in environmental and analytical monitoring. The approaches to the estimation of kinetic parameters of inhibition are reviewed and the factors determining the selectivity and sensitivity of inhibitor assays in environmental objects are analysed. The bibliography includes 195 references.

  6. PREVENTION OF ANTRACYCLIN ANTIBIOTIC DOXORUBICIN СARDIOTOXICITY: A ROLE OF ACE-INHIBITOR PERINDOPRIL

    E. V. Pravdivtseva

    2014-07-01

    Full Text Available Aim – to study how anthracyclines influence on cardiovascular system in patients with lymphomas and whether angiotensin-converting enzyme inhibitor Perindopril is cardioprotective in these patients.Subjects and methods. 26 patients with Hodgkin’s disease and non-Hodgkin’s lymphomas were followed before and after treatment withdoxorubicin. 12 of these patients with arterial hypertension received angiotensin-converting enzyme inhibitor Рerindopril, 10 mg/d, duringtreatment with doxorubicin. Cardiological evaluation was performed before and the next day after chemotherapy. Average dose of Doxorubicin was 34,99 ± 13,23 mg/m2.Results. In patients receiving anthracyclines deceleration time DT increased significantly, a significant reduction in heart rate (HR, cardiacoutput (CO and cardiac index (CI were observed also (рDT = 0,037, pHR = 0,048, рСО = 0,007, рCI = 0,007. In patients simultaneouslytreated with Perindopril these parameters were not statistically different (рDT = 0,92, pHR = 0,22, рCO = 0,35, рCI = 0,39.Conclusion. Administration of anthracyclines (average dose of Doxorubicin 34,99 ± 13,23 mg/m2 leads to DT of the left ventricle andreduction in HR, CJ and CI. Simultaneous treatment with Perindopril in patients receiving anthracyclines preserves DF and prevents heart hemodynamics abnormalities.

  7. PREVENTION OF ANTRACYCLIN ANTIBIOTIC DOXORUBICIN СARDIOTOXICITY: A ROLE OF ACE-INHIBITOR PERINDOPRIL

    E. V. Pravdivtseva

    2011-01-01

    Full Text Available Aim – to study how anthracyclines influence on cardiovascular system in patients with lymphomas and whether angiotensin-converting enzyme inhibitor Perindopril is cardioprotective in these patients.Subjects and methods. 26 patients with Hodgkin’s disease and non-Hodgkin’s lymphomas were followed before and after treatment withdoxorubicin. 12 of these patients with arterial hypertension received angiotensin-converting enzyme inhibitor Рerindopril, 10 mg/d, duringtreatment with doxorubicin. Cardiological evaluation was performed before and the next day after chemotherapy. Average dose of Doxorubicin was 34,99 ± 13,23 mg/m2.Results. In patients receiving anthracyclines deceleration time DT increased significantly, a significant reduction in heart rate (HR, cardiacoutput (CO and cardiac index (CI were observed also (рDT = 0,037, pHR = 0,048, рСО = 0,007, рCI = 0,007. In patients simultaneouslytreated with Perindopril these parameters were not statistically different (рDT = 0,92, pHR = 0,22, рCO = 0,35, рCI = 0,39.Conclusion. Administration of anthracyclines (average dose of Doxorubicin 34,99 ± 13,23 mg/m2 leads to DT of the left ventricle andreduction in HR, CJ and CI. Simultaneous treatment with Perindopril in patients receiving anthracyclines preserves DF and prevents heart hemodynamics abnormalities.

  8. Lisinopril and Hydrochlorothiazide

    ... a class of medications called angiotensin-converting enzyme (ACE) inhibitors. It works by decreasing certain chemicals that tighten ... lisinopril; hydrochlorothiazide (HCTZ, Microzide, Oretic); angiotensin-converting ... such as benazepril (Lotensin), captopril (Capoten), enalapril (Vasotec , ...

  9. Angiotensin I-Converting Enzyme Inhibitor Derived from Cross-Linked Oyster Protein

    Cheng-Liang Xie

    2014-01-01

    Full Text Available Following cross-linking by microbial transglutaminase, modified oyster proteins were hydrolyzed to improve inhibitory activity against angiotensin-converting enzyme (ACE inhibitory activity with the use of a single protease, or a combination of six proteases. The oyster hydrolysate with the lowest 50% ACE inhibitory concentration (IC50 of 0.40 mg/mL was obtained by two-step hydrolysis of the cross-linked oyster protein using Protamex and Neutrase. Five ACE inhibitory peptides were purified from the oyster hydrolysate using a multistep chromatographic procedure comprised of ion-exchange, size exclusion, and reversed-phase liquid chromatography. Their sequences were identified as TAY, VK, KY, FYN, and YA, using automated Edman degradation and mass spectrometry. These peptides were synthesized, and their IC50 values were measured to be 16.7, 29.0, 51.5, 68.2, and 93.9 μM, respectively. Toxicity of the peptides on the HepG2 cell line was not detected. The oyster hydrolysate also significantly decreased the systolic blood pressure of spontaneously hypertensive rats (SHR. The antihypertensive effect of the oyster hydrolysate on SHR was rapid and long-lasting, compared to commercially obtained sardine hydrolysate. These results suggest that the oyster hydrolysate could be a source of effective nutraceuticals against hypertension.

  10. Interaction and Relationship Between Angiotensin Converting Enzyme Gene and Environmental Factors Predisposing to Essential Hypertension in Mongolian Population of China

    QUN XU; HUA FENG; SHUANG-LIAN BAI; HAI-HUA PANG; GUI-RONG HUANG; MING-WU FANG; YONG-HONG ZHANG; ZHENG-LAI WU; CHANG-CHUN QIU; YAN-HUA WANG; WEI-JUN TONG; MING-LIANG GU; GANG WU; BATU BUREN; YONG-YUE LIU; JIAN WANG; YONG-SHAN LI

    2004-01-01

    Objective To investigate the association of specific functional gene ACE (I/D) variants of the renin-angiotensin system with essential hypertension (EH) and interaction between ACE (I/D) gene and risk factors for EH in a genetically homogenous Mongolia rural population of China. Methods Individuals (n=1099) were recruited from general population of Kezuohouqi Banner in Inner Mongolian Autonomous Region. Results The association was found between ACE genotype DD plus ID and EH, with an interaction between ACE genotype DD plus ID and cigarette smoking in an additive model. Cigarette smoking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 7.10 to 1.16. Interaction between ACE genotype DD plus ID and alcohol drinking on EH appeared an additive model. Alcohol drinking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 1.66 to 1.09. BMI and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 6.15 to 2.49. Interactions between ACE genotype and WHR on EH showed a multiplicative model. In a short, there was an interaction between ACE gene and cigarette smoking, alcohol drinking and BMI on EH, especially in a low dose-exposure effect. Conclusion It is important for individuals who carry ACE D allele gene to prevent EH, and furthermore, to prevent and control coronary heart disease, in a view of population-based prevention.

  11. Hypotensive Effects and Angiotensin-Converting Enzyme Inhibitory Peptides of Reishi (Ganoderma lingzhi Auto-Digested Extract

    Hai-Bang Tran

    2014-08-01

    Full Text Available Reishi (Ganoderma lingzhi has been used as a traditional medicine for millennia. However, relatively little is known about this mushroom’s proteins and their bioactivities. In this study, we used reishi’s own proteases to hydrolyze its protein and obtained auto-digested reishi (ADR extract. The extract was subjected to in vitro assays and administered to spontaneous hypertensive rats (SHRs to determine its potential for use as a hypotensive medication. Bioassay-guided fractionation and de novo sequencing were used for identifying the active compounds. After 4 h administration of ADR, the systolic pressure of SHRs significantly decreased to 34.3 mmHg (19.5% change and the effect was maintained up to 8 h of administration, with the decrease reaching as low as 26.8 mmHg (15% reduction–compare to base line a decrease of 26.8 mmHg is less than a decrease of 34.3 mmHg so it should give a smaller % reduction. Eleven peptides were identified and four of them showed potent inhibition against ACE with IC50 values ranging from 73.1 μM to 162.7 μM. The results showed that ADR could be a good source of hypotensive peptides that could be used for antihypertensive medication or incorporation into functional foods.

  12. Bradykinin Type 2 Receptor BE1 Genotype Influences Bradykinin-Dependent Vasodilation During Angiotensin-Converting Enzyme Inhibition

    Van Guilder, Gary P.; Pretorius, Mias; Luther, James M.; Byrd, J. Brian; Hill, Kevin; Gainer, James V.; Brown, Nancy J.

    2008-01-01

    To test the hypothesis that the bradykinin receptor 2 (BDKRB2) BE1 +9/−9 polymorphism affects vascular responses to bradykinin, we measured the effect of intra-arterial bradykinin on forearm blood flow and tissue-type plasminogen activator (t-PA) release in 89 normotensive, nonsmoking, white American subjects in whom degradation of bradykinin was blocked by enalaprilat. BE1 genotype frequencies were +9/+9:+9/−9:−9/−9=19:42:28. BE1 genotype was associated with systolic blood pressure (121.4±2....

  13. Short-term hemodynamic effect of angiotensin-converting enzyme inhibition in patients with severe aortic stenosis

    Dalsgaard, Morten; Iversen, Kasper; Kjaergaard, Jesper;

    2014-01-01

    of 8 weeks, when exercise echocardiography was repeated. RESULTS: Compared with placebo, systolic blood pressure and systemic arterial compliance significantly changed at day 3 (-14 ± 11 vs -5 ± 13 mm Hg, P = .02, and 0.08 ± 0.16 vs -0.05 ± 0.86 mL/m(2) per mm Hg, P = .03, respectively). Changes in...

  14. Genetic variation in angiotensin-converting enzyme 2 gene is associated with extent of left ventricular hypertrophy in hypertrophic cardiomyopathy

    van der Merwe, Lize; Cloete, Ruben; Revera, Miriam; Heradien, Marshall; Goosen, Althea; Corfield, Valerie A.; Paul A Brink; Moolman-Smook, Johanna C

    2008-01-01

    Hypertrophic cardiomyopathy, a common, inherited cardiac muscle disease, is primarily caused by mutations in sarcomeric protein-encoding genes and is characterized by overgrowth of ventricular muscle that is highly variable in extent and location. This variability has been partially attributed to locus and allelic heterogeneity of the disease-causing gene, but other factors, including unknown genetic factors, also modulate the extent of hypertrophy that develops in response to the defective s...

  15. ROLE OF ANGIOTENSIN-CONVERTING ENZYME AND VITAMIN D RECEPTOR GENE POLYMORPHISMS IN CANCER ANOREXIA-CACHEXIA SYNDROME

    Ariele Fabris; Paolo Biagioni; Tiziana Punzi; Gabriele Morucci; Massimo Gulisano; Stefania Pacini; Marco Ruggiero

    2012-01-01

    The ubiquitin-proteasome pathway is a crucial connection between aberrant immune system activation, systemic inflammation and Cancer Anorexia-Cachexia Syndrome (CACS), a syndrome that culminates in hyper-activation of the ubiquitin-proteasome pathway. Angiotensin directly up-regulates this pathway, while vitamin D down-regulates it indirectly through the insulin-like growth factor-1 pathway. We investigated the genetic predisposition towards CACS in a cancer population, examining Insertion/De...

  16. 降血压肽的研究进展%Research progress of angiotensin converting enzyme inhibitory peptides

    高沛; 吴靖娜; 许永安

    2012-01-01

    本文主要从降血压肽的作用机理、制备方法、分离纯化技术及活性测定手段等方面,结合国内外的相关研究,综述了降血压肽领域的研究进展。并在此基础上,展望了食源性降血压肽于医疗保健方面的发展前景。旨在为降血压肽的进一步深入研究提供依据,为其产业化生产及市场推广提供参考,为降血压治疗提供新的选择。%In this article, combining with domestic and foreign researches, we reviews the research progress of antihypertensive peptides including the mechanism, preparation method, separation and purification tech- nology, and activity determination means. On this basis, we also gives prospect of the foodborne antihyper- tensive peptides in medical care development. The paper will provide a basis for further studies of the food- borne antihypertensive peptides. It will be an useful reference for antihypertensive peptide industrial produc- tion and marketing, and provide new options for hypertension treatment.

  17. Plasminogen activator inhibitor-1: physiologic role, regulation, and the influence of common pharmacologic agents.

    Tsikouris, James P; Suarez, Jose A; Meyerrose, Gary E

    2002-11-01

    Plasminogen activator inhibitor-1 (PAI-1) is the major inhibitor of endogenous thrombolysis, thereby promoting thrombosis. PAI-1 is also a primary contributor to the development and recurrence of acute myocardial infarction. The renin angiotensin system, hypertriglyceridemia, hyperglycemia and hyperinsulinemia, and estrogen all influence the fibrinolytic system and PAI-1 in particular. Available data strongly suggest that angiotensin-converting enzyme (ACE) inhibitors and hormone replacement therapy with estrogen beneficially reduce PAI-1 production. Metformin, an agent commonly used for non-insulin-dependent diabetes mellitus (NIDDM), appears to favorably decrease PAI-1 production in NIDDM patients but not nondiabetic patients. Among the cholesterol-lowering statins, clinical literature evaluating pravastatin provides the most compelling data to support this agent's favorable effect on PAI-1. Other available statins either have not displayed an effect on PAI-1 or do not have clear data to conclusively define their effects on the fibrinolytic system. PMID:12412817

  18. A metal-based inhibitor of NEDD8-activating enzyme.

    Hai-Jing Zhong

    Full Text Available A cyclometallated rhodium(III complex [Rh(ppy(2(dppz](+ (1 (where ppy=2-phenylpyridine and dppz=dipyrido[3,2-a:2',3'-c]phenazine dipyridophenazine has been prepared and identified as an inhibitor of NEDD8-activating enzyme (NAE. The complex inhibited NAE activity in cell-free and cell-based assays, and suppressed the CRL-regulated substrate degradation and NF-κB activation in human cancer cells with potency comparable to known NAE inhibitor MLN4924. Molecular modeling analysis suggested that the overall binding mode of 1 within the binding pocket of the APPBP1/UBA3 heterodimer resembled that for MLN4924. Complex 1 is the first metal complex reported to suppress the NEDDylation pathway via inhibition of the NEDD8-activating enzyme.

  19. Nutritional significance of lectins and enzyme inhibitors from legumes.

    Lajolo, Franco M; Genovese, Maria Inés

    2002-10-23

    Legumes have natural components, such as lectins, amylase, and trypsin inhibitors, that may adversely affect their nutritional properties. Much information has already been obtained on their antinutritional significance and how to inactivate them by proper processing. Chronic ingestion of residual levels is unlikely to pose risks to human health. On the other hand, the ability of these molecules to inhibit some enzymes such as trypsin, chymotrypsin, disaccharidases, and alpha-amylases, to selectively bind to glycoconjugates, and to enter the circulatory system may be a useful tool in nutrition and pharmacology. Trypsin inhibitors have also been studied as cancer risk reducing factors. These components seem to act as plant defense substances. However, increased contents may represent an impairment of the nutritional quality of legumes because these glycoproteins and the sulfur-rich protease inhibitors have been shown to be poorly digested and to participate in chemical reactions during processing reducing protein digestibility, a still unsolved question. PMID:12381157

  20. ACE抑制剂与A Ⅱ受体阻滞剂治疗慢性心力衰竭的临床试验%Clinical Trials of Effects of Angiotensin Converting Enzyme Inhibitors and Angiotensin Ⅱ Receptor Blockers in Chronic Heart Failure

    季闽春; 耿晓芳; 殷民德

    2001-01-01

    许多临床试验证明ACE抑制剂和AⅡ受体阻滞剂是治疗慢性心力衰竭的有效药物,它们的作用存在明显的剂量效应,大剂量的作用优于小剂量.两药合用有协同作用.临床实践中应根据病人的耐受情况选用推荐剂量或靶剂量.

  1. 高血压患者服用血管紧张素转换酶抑制剂后咳嗽机制的前瞻性研究%A prospective study on the cough mechanism induced by angiotensin-converting enzyme inhibitors in patients with hypertension

    叶阮健; 何权瀛; 改军; 尚颖

    2004-01-01

    目的观察原发性高血压患者的性别、服药种类、吸烟习惯、血管紧张素转换酶(ACE)基因多态性及其服药前、后血清ACE水平变化与咳嗽的关系及研究服用ACE抑制剂(ACEI)类药物后发生咳嗽的机制.方法入选高血压患者127例,依据服用ACEI(97例口服西拉普利、30例口服盐酸贝那普利)8周后是否出现咳嗽分为咳嗽组(48例)和不咳嗽组(79例).比较两组ACE基因多态性(II型、ID型、DD型)及服药前、后血清ACE水平的差异,并将相关因素进行Logistic回归分析,预测出是否咳嗽的方程式.结果 127例患者中有48例 (37.8%)出现咳嗽.咳嗽组ACE的I等位基因及II基因型频率分布分别为0.70%和56.3%,不咳嗽组分别为0.42%和23.3%,两组比较差异有显著性(P<0.05).咳嗽组服药前、后血清ACE水平分别为 (26±6)U/L、(4±4)U/L,不咳嗽组分别为(33±8)U/L、(8±8)U/L,两组服药前、后血清ACE水平比较差异有显著性﹙ P 均<0.01).咳嗽组和不咳嗽组服药前、后血清ACE水平变化幅度分别为 (22±7)U/L、 (25±9) U/L,两组血清ACE水平变化幅度比较差异无显著性﹙ P=0.077).服药前血清ACE水平DD型最高[(36±8) U/L], ID型次之[(29±6)U/L],II型最低[(26±7)U/L],服药前3个基因型间比较差异有显著性(P<0.01).全部病例中咳嗽与否与性别、吸烟、服药种类无关.得到判断是否咳嗽的概率值的回归方程.结论 (1)血清ACE水平与ACE基因多态性相关,ACE基因II型和I等位基因与服用ACEI药物引起的咳嗽相关,服药前患者血清ACE水平与服药后咳嗽相关;(2)公式预测服药后不咳嗽的正确率高.

  2. Correlation Analysis of Polymorphisms of Angiotensin Converting Enzyme Gene,Plasminogen Activator Inhibitor-1 Gene and Nephropathy in Type 2 Diabetes%血管紧张素Ⅰ转换酶、血浆纤溶酶原激活物抑制剂基因多态性与2型糖尿病肾病相关性分析

    颜晓芳; 潘时中; 杨立勇; 黄凌宁; 赵淑好

    2008-01-01

    目的 探讨血管紧张素Ⅰ转换酶(ACE)、血浆纤溶酶原激活物抑制剂(PAI-1)基因多态性与2型糖尿病肾病的相关性.方法 58例健康者为对照组、92例糖尿病非肾病患者为糖尿病非肾病组、125例糖尿病肾病患者为糖尿病肾病组,聚合酶链反应确定ACE、PAI-1基因型.酶联免疫吸附法检测血浆PAI-1.结果 糖尿病肾病组ACE基因中D等位基因频率、PAI-1基因中4G等位基因频率明显高于糖尿病非肾病组、对照组.Logistic回归分析表明ACE、PAI-1基因是2型糖尿病肾病的危险因素.结论 ACE基因中D等位基因、PAI-1基因中4G等位基因可能涉及2型糖尿病肾病发病.

  3. Characterization of inhibitor(s) of β-glucuronidase enzyme activity in GUS-transgenic wheat

    Ramadan, Ahmed M Ali

    2011-06-26

    The uidA gene, encoding for β-glucuronidase (GUS), is the most frequently used reporter gene in plants. As a reporter enzyme, GUS can be assayed both qualitatively and quantitatively. In wheat, there are numerous reports of failure in detecting GUS enzyme activity in tissues of transgenic plants, while other reports have suggested presence of β-glucuronidase inhibitor(s) in wheat tissues. In the present study, we show that the β-glucuronidase enzyme activity is not only tissue-specific but also genotype-dependent. Our data demonstrate that the glucuronic acid could be the candidate inhibitor for β-glucuronidase enzyme activity in wheat leaves and roots. It should be noted that the assays to detect β-glucuronidase enzyme activity in wheat should be interpreted carefully. Based on the data of our present study, we recommend studying the chemical pathways, the unintended effects and the possible loss-of-function of any candidate transgene prior to transformation experiments. © 2011 Springer Science+Business Media B.V.

  4. A New Sucrase Enzyme Inhibitor from Azadirachta indica

    Abdelhady, Mohamed I. S.; Shaheen, Usama; Bader, Ammar; Youns, Mahmoud A.

    2016-01-01

    Background: Sucrase enzyme inhibitor considered as an oral anti-diabetic therapy that delays the absorption of eaten carbohydrates, reducing the postprandial glucose and insulin peaks to reach normoglycemia. Materials and Methods: Chromatographic fractionation of the hydroalcoholic extract of leaves of Azadirachta indica growing in KSA, followed by in-vitro assay of sucrase enzyme inhibition activity. Results: This investigation led to the isolation of a new remarkable sucrase enzyme inhibitor; 4’-methyl Quercetin-7-O-β-D-glucuronopyranoside (1) alongside with four known compounds; 2,3-hexahydroxydiphenoyl-(α/β)-D-4C1-glucopyranose (2), Avicularin (3), Castalagin (4) and Quercetin-3-O-glucoside (5). The structure of the new compound (1) was elucidated on the basis of its spectral data, including ESI-MS, UV, 1H NMR, 13C NMR, 1H-1H COSY, HSQC, NOESY and HMBC. Conclusion: Under the assay conditions, hydroalcoholic extract of A. indica and compounds 1-5 exhibited significant sucrase enzyme inhibitory activity. SUMMARY Chromatographic fractionation of the hydroalcoholic extract of leaves of Azadirachta indica, led to the Isolation of a new flavonoid glycoside named 4’-methyl Quercetin-7-O-β-D-glucuronopyranoside, alongside to other 4 known polyphenols. The hydroalcoholic extract as well as the isolated compounds exhibited significant sucrase enzyme inhibitory activity. Abbreviations used: ESI-MS; electrospray ionization-mass spectrometry, UV; ultraviolet, NMR; nuclear magnetic resonance, 1H-1H COSY; 1H-1H correlation spectroscopy, NOESY; nuclear overhauser effect spectroscopy, and HSQC; heteronuclear multiple bond correlation. A. indica; Azadirachta indica.

  5. 脂多糖对大鼠肺微血管内皮细胞ACE和ACE2表达的影响及血管紧张素转换酶抑制剂的干预作用%Effects of lipolysaccharide on expression of ACE and ACE2 in rat pulmonary microvascular endothelial cells and intervention effects of angiotensinconverting enzyme inhibitor

    李亚春; 李颖川; 周明; 江伟

    2012-01-01

    目的 观察脂多糖(LPS)对大鼠肺微血管内皮细胞(PMVECs)血管紧张素转换酶(ACE)和血管紧张素转换酶2(ACE2)表达的影响及血管紧张素转换酶抑制剂( ACEI) Captopril的干预作用.方法 组织块法体外培养大鼠PMVECs,观察LPS对PMVECs作用的时间和浓度相关毒性以及Captopril的干预作用;再将PMVECs随机分为4组:对照组(n=6),不加干预措施;Captopril组(n=6),10-5mol/L Captopril孵育细胞8 h;LPS组(n=6),1 mg/mL LPS孵育细胞8 h;Captoril+ LPS组(n=6),10-5 moL/L Captopril孵育细胞30 min后再加入1 mg/mL LPS孵育8h.CCK8检测细胞活性;Western blotting法检测各组细胞ACE和ACE2的表达.结果 LPS可对大鼠PMECs产生明显的毒性作用,并可使细胞ACE表达上调及ACE2表达下降;经Captopril干预后,可明显抑制LPS的细胞毒性作用,并逆转LPS对PMVECs中ACE及ACE2表达的影响,使ACE和ACE2表达水平回调至对照组水平.结论ACEI能减轻LPS所致的PMVECs毒性作用,而ACE及ACE2表达的变化可能在这一过程中起重要作用.%Objective To investigate the effects of lipolysaccharide (LPS) on expression of angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) in rat pulmonary microvaeculai endothelial cells (PMVECs) and the intervention effects of angiotensin-converting enzyme inhibitor (ACEI) Captopril. Methods Rat PMVECs were cultured in vitro with tissue explants adherant method, the toxic effects of LPS on PMVECs were investigated by treatment of PMVECs with different concentrations of LPS for different time, and the intervention effects of Captopril were observed. PMVECs were randomly divided into control group (without intervention, n = 6), Captopril group (treatment with 10 -5 mol/L Captopril for 8 h, n =6), LPS group (treatment with 1 mg/mL LPS for 8 h, n =6) and Captoril + LPS group (treatment with 10 -5 mol/L Captopril for 30 min and 1 mg/mL LPS for 8 h, n =6) . Cell viability was determined by CCK8, and the

  6. Sarcoidosis patient: an unexpected reaction to carbonic anhydrase enzyme inhibitor

    Khedr, Yahya A H; Khedr, Abdulla H

    2013-01-01

    Ocular diseases are very common in many of the systemic diseases such as sarcoidosis, and may sometimes be the presenting symptom of the disease. In this case report, we present an unusual reaction of the sarcoid granuloma to carbonic anhydrase enzyme inhibitors (CAIs), which was encountered in a patient with ocular sarcoidosis. This observation was taken after a 2-week interval between a CT scan orbits and an MRI orbits which showed a decrease in size from 4×3×4 cm to 2.5×2.5×2 cm, respectiv...

  7. Future prospects of antibacterial metal nanoparticles as enzyme inhibitor.

    Ahmed, Khan Behlol Ayaz; Raman, Thiagarajan; Veerappan, Anbazhagan

    2016-11-01

    Nanoparticles are being widely used as antibacterial agents with metal nanoparticles emerging as the most efficient antibacterial agents. There have been many studies which have reported the mechanism of antibacterial activity of nanoparticles on bacteria. In this review we aim to emphasize on all the possible mechanisms which are involved in the antibacterial activity of nanoparticles and also to understand their mode of action and role as bacterial enzyme inhibitor by comparing their antibacterial mechanism to that of antibiotics with enzyme inhibition as a major mechanism. With the emergence of widespread antibiotic resistance, nanoparticles offer a better alternative to our conventional arsenal of antibiotics. Once the biological safety of these nanoparticles is addressed, these nanoparticles can be of great medical importance in our fight against bacterial infections. PMID:27524096

  8. Identification of selective enzyme inhibitors by fragment library screening.

    Gao, Geng; Liu, Xuying; Pavlovsky, Alexander; Viola, Ronald E

    2010-10-01

    The microbial threat to human health is growing due to the dramatic increase in the number of multidrug-resistant organisms. The decline in effective antibiotics available to treat these growing threats has provided greater urgency to the search for new antibiotics. Clearly, new approaches must be developed against novel targets to control these resistant infectious organisms. The screening of low molecular weight compounds against new protein targets provides an opportunity to identify novel inhibitors as starting points for the development of new antibiotics. Custom fragment libraries have been assembled and screened against 3 representative forms of a key enzyme in an essential microbial biosynthetic pathway. Although each of these aspartate semialdehyde dehydrogenases (ASADHs) catalyzes the same reaction and each shares identical active site functional groups, subtle differences in enzyme structures have led to different binding selectivity among the initial hits from these fragment libraries. Amino acid analogues have been identified that show selectivity for either the gram-negative or gram-positive bacterial enzyme forms. A series of benzophenone analogues selectively inhibit the gram-negative ASADH, whereas some haloacids and substituted aromatic acids have been found to inhibit only the fungal form of ASADH. Each of these low molecular weight compounds possesses high ligand binding efficiency for their target enzyme forms. These results support the goal of designing lead compounds that will selectively target ASADHs from different microbial species. PMID:20855558

  9. Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group

    Flather, M D; Yusuf, S; Køber, L;

    2000-01-01

    BACKGROUND: We undertook a prospective systematic overview based on data from individual patients from five long-term randomised trials that assessed inhibitors of angiotensin-converting enzyme (ACE) in patients with left-ventricular dysfunction or heart failure. METHODS: Three of the trials...... was lower with ACE inhibitors than with placebo (702/2995 [23.4%] vs 866/2971 [29.1%]; odds ratio 0.74 [95% CI 0.66-0-83]), as were the rates of readmission for heart failure (355 [11.9%] vs 460 [15.5%]; 0.73 [0.63-0.85]), reinfarction (324 [10.8%] vs 391 [13.2%]; 0.80 [0.69-0.94]), or the composite...

  10. Using Trypsin & Soybean Trypsin Inhibitor to Teach Principles of Enzyme Kinetics

    Howard, David R.; Herr, Julie; Hollister, Rhiannon

    2006-01-01

    Trypsin and soybean trypsin inhibitor (Kunitz inhibitor) can be used in a relatively simple and inexpensive student exercise to demonstrate the usefulness of enzyme kinetics. The study of enzyme kinetics is essential to biology because enzymes play such a crucial role in the biochemical pathways of all living organisms. The data from enzyme…

  11. Cardiovascular risk reduction by reversing endothelial dysfunction: ARBs, ACE inhibitors,  or both? Expectations from The ONTARGET  Trial Programme

    Luis Miguel  Ruilope

    2007-03-01

    Full Text Available Luis Miguel  Ruilope1, Josep Redón2, Roland Schmieder31Servicio de Nefrologia, Unidad de Hipertension Hospital, 12 de Octubre, Madrid, Spain; 2Department of Internal Medicine, Hospital Clinico University of Valencia, Valencia, Spain; 3Department of Nephrology and Hypertension, Friedrich-Alexander-Universitat, Erlangen-Nurnberg, GermanyAbstract: Endothelial dysfunction is the initial pathophysiological step in a progression of vascular damage that leads to overt cardiovascular and chronic kidney disease. Angiotensin II, the primary agent of the renin–angiotensin system (RAS, has a central role in endothelial dysfunction. Therefore, RAS blockade with an angiotensin receptor blocker (ARB and/or angiotensin-converting enzyme (ACE inhibitor provides a rational approach to reverse endothelial dysfunction, reduce microalbuminuria, and, thus, improves cardiovascular and renal prognosis. ARBs and ACE inhibitors act at different points in the RAS pathway and recent evidence suggests that there are differences regarding their effects on endothelial dysfunction. In addition to blood pressure lowering, studies have shown that ARBs reduce target-organ damage, including improvements in endothelial dysfunction, arterial stiffness, the progression of renal dysfunction in patients with type 2 diabetes, proteinuria, and left ventricular hypertrophy. The ONgoing Telmisartan Alone in combination with Ramipril Global Endpoint Trial (ONTARGET Programme is expected to provide the ultimate evidence of whether improved endothelial func tion translates into reduced cardiovascular and renal events in high-risk patients, and to assess possible differential outcomes with telmisartan, the ACE inhibitor ramipril, or a combination of both (dual RAS blockade. Completion of ONTARGET is expected in 2008. Keywords: angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, endothelial dysfunction, ONTARGET, renin–angiotensin system, telmisartan

  12. Plant Protein Inhibitors of Enzymes: Their Role in Animal Nutrition and Plant Defence.

    Richardson, Michael

    1981-01-01

    Current information and research related to plant protein inhibitors of enzymes are reviewed, including potential uses of the inhibitors for medical treatment and for breeding plant varieties with greater resistance to insects. (DC)

  13. Are the angiotensin-converting enzime gene and acticity risk factors for stroke? São fatores de risco para acidente vascular cerebral o gene e a atividade da enzima conversora de angiotensina ?

    Miris Dikmen

    2006-06-01

    Full Text Available Stroke is a multifactorial disease in which genetic factors play an important role. This study was carried out to determine angiotensin-converting enzyme (ACE gene polymorphism in Turkish acute stroke patients and to establish whether there is an association of angiotensin-converting enzyme gene I/D polymorphism with clinical parameters. In this study 185 patients and 50 controls were recruited. We have investigated the association among the allelic distribution of the insertion/deletion (I/D polymorphism of the ACE gene identified by polymerase chain reaction. Distribution of ACE gene I/D genotypes and allele frequencies in patients were not significantly different from controls. D allele frequencies were 57.8% in patients versus 53.0% in controls and I allele 42.2% versus 47% respectively. History of hypertension, stroke, renal, heart and vessel diseases incidence and age, gender, systolic-diastolic blood pressures and creatinine levels were significantly high in patients. But these results and ACE activities had no significant differences among the ACE genotypes in patients and controls. Our results suggest that the ACE gene polymorphism is not associated with the pathogenesis of stroke in Turkish stroke patients.O acidente vascular cerebral (AVC é doença multifatorial em que fatores genéticos desempenham papel importante. Este estudo foi desenvolvido para verificar o polimorfismo do gene da enzima conversora da angiotensina (ECA em pacientes turcos com AVC agudo e estabelecer se existe associação do gene I/D da ECA com parâmetros clínicos. O estudo foi realizado com 185 pacientes e 50 controles. A associação entre a distribuição alélica da inserção / deleção (I/D do polimorfismo do gene da ECA foi estudada pela reação em cadeia da polimerase. A distribuição dos genótipos I/D do gene da ECA e suas freqüências não apresentaram significância estatística quando comparados os pacientes e controles. As freqüências dos

  14. Chronic ACE inhibitor treatment increases angiotensin type 1 receptor binding in vivo in the dog kidney

    PET imaging has been recently introduced for investigating the type 1 angiotensin II receptor (AT1R) in vivo. The goal of the present study was to investigate the effects of acute and chronic exposure to angiotensin converting enzyme inhibitors (ACEI) on the AT1R in the dog kidney. Animals were imaged at baseline, after acute intravenous ACEI treatment and after a chronic 2-week exposure to an oral ACEI. Control animals were imaged at identical time points in the absence of ACEI treatment. In vivo AT1R binding expressed by Ki was increased in the renal cortex by chronic ACEI treatment (p 1R density (Bmax) also revealed significant increases in AT1R in isolated glomeruli (p 1R binding in vivo in the dog renal cortex. (orig.)

  15. Blocking the RAAS at different levels: an update on the use of the direct renin inhibitors alone and in combination

    Francesca Cagnoni

    2010-06-01

    Full Text Available Francesca Cagnoni1, Christian Achiri Ngu Njwe1, Augusto Zaninelli4, Alessandra Rossi Ricci1, Diletta Daffra2, Antonio D’Ospina1, Paola Preti3, Maurizio Destro11Internal Medicine, Ospedale Unificato Broni-Stradella, Stradella (PV, Italy; 2Internal Medicine, S.S. Annunziata Hospital, Varzi (PV, Italy; 3Internal Medicine, University of Pavia, Pavia, Italy; 4School of Medicine, University of Florence, Florence, ItalyAbstract: The renin–angiotensin–aldosterone system (RAAS, an important regulator of blood pressure and mediator of hypertension-related complications, is a prime target for cardiovascular drug therapy. Angiotensin-converting enzyme inhibitors (ACEIs were the first drugs to be used to block the RAAS. Angiotensin II receptor blockers (ARBs have also been shown to be equally effective for treatment. Although these drugs are highly effective and are widely used in the management of hypertension, current treatment regimens with ACEIs and ARBs are unable to completely suppress the RAAS. Combinations of ACEIs and ARBs have been shown to be superior than to either agent alone for some, but certainly not all, composite cardiovascular and kidney outcomes, but dual RAAS blockade with the combination of an ACEI and an ARB is sometimes associated with an increase in the risk for adverse events, primarily hyperkalemia and worsening renal function. The recent introduction of the direct renin inhibitor, aliskiren, has made available new combination strategies to obtain a more complete blockade of the RAAS with fewer adverse events. Renin system blockade with aliskiren and another RAAS agent has been, and still is, the subject of many large-scale clinical trials and furthermore, is already available in some countries as a fixed combination. Keywords: angiotensin II receptor blockers, renin–angiotensin–aldosterone system, hypertension, angiotensin-converting enzyme inhibitors

  16. Screening for Enzyme Inhibitors by Surface Plasmon Resonance Combined with Mass Spectrometry

    Borch, Jonas; Roepstorff, Peter

    2004-01-01

    substrate and mass spectrometric analysis. If the bound compound inhibits the enzyme, the inhibitor is eluted from the enzyme and characterized by mass spectrometry. To test the strategy, it has been applied to the well-characterized interaction between trypsin and pure bovine pancreas trypsin inhibitor...

  17. Unraveling the Pivotal Role of Bradykinin in ACE Inhibitor Activity.

    Taddei, Stefano; Bortolotto, L

    2016-10-01

    Historically, the first described effect of an angiotensin converting enzyme (ACE) inhibitor was an increased activity of bradykinin, one of the substrates of ACE. However, in the subsequent years, molecular models describing the mechanism of action of ACE inhibitors in decreasing blood pressure and cardiovascular risk have focused mostly on the renin-angiotensin system. Nonetheless, over the last 20 years, the importance of bradykinin in regulating vasodilation, natriuresis, oxidative stress, fibrinolysis, inflammation, and apoptosis has become clearer. The affinity of ACE appears to be higher for bradykinin than for angiotensin I, thereby suggesting that ACE inhibitors may be more effective inhibitors of bradykinin degradation than of angiotensin II production. Data describing the effect of ACE inhibition on bradykinin signaling support the hypothesis that the most cardioprotective benefits attributed to ACE inhibition may be due to increased bradykinin signaling rather than to decreased angiotensin II signaling, especially when high dosages of ACE inhibitors are considered. In particular, modulation of bradykinin in the endothelium appears to be a major target of ACE inhibition. These new mechanistic concepts may lead to further development of strategies enhancing the bradykinin signaling. PMID:27260014

  18. Identification and Characterization of New Inhibitors of the Escherichia coli MurA Enzyme

    Baum, Ellen Z.; Montenegro, Deborah A.; Licata, Lisa; Turchi, Ignatius; Webb, Glenda C.; Foleno, Barbara D.; Bush, Karen

    2001-01-01

    The bacterial enzyme MurA catalyzes the transfer of enolpyruvate from phosphoenolpyruvate (PEP) to uridine diphospho-N-acetylglucosamine (UNAG), which is the first committed step of bacterial cell wall biosynthesis. From high-throughput screening of a chemical library, three novel inhibitors of the Escherichia coli MurA enzyme were identified: the cyclic disulfide RWJ-3981, the purine analog RWJ-140998, and the pyrazolopyrimidine RWJ-110192. When MurA was preincubated with inhibitor, followed...

  19. Action of plant proteinase inhibitors on enzymes of physiopathological importance

    Oliva, Maria Luiza V.; Sampaio, Misako U.

    2009-01-01

    Obtained from leguminous seeds, various plant proteins inhibit animal proteinases, including human, and can be considered for the development of compounds with biological activity. Inhibitors from the Bowman-Birk and plant Kunitz-type family have been characterized by proteinase specificity, primary structure and reactive site. Our group mostly studies the genus Bauhinia, mainly the species bauhinioides, rufa, ungulata and variegata. In some species, more than one inhibitor was characterized,...

  20. Enzyme inhibitor studies reveal complex control of methyl-D-erythritol 4-phosphate (MEP pathway enzyme expression in Catharanthus roseus.

    Mei Han

    Full Text Available In Catharanthus roseus, the monoterpene moiety exerts a strong flux control for monoterpene indole alkaloid (MIA formation. Monoterpene synthesis depends on the methyl-D-erythritol 4-phosphate (MEP pathway. Here, we have explored the regulation of this pathway in response to developmental and environmental cues and in response to specific enzyme inhibitors. For the MEP pathway entry enzyme 1-deoxy-D-xylulose 5-phosphate synthase (DXS, a new (type I DXS isoform, CrDXS1, has been cloned, which, in contrast to previous reports on type II CrDXS, was not transcriptionally activated by the transcription factor ORCA3. Regulation of the MEP pathway in response to metabolic perturbations has been explored using the enzyme inhibitors clomazone (precursor of 5-ketochlomazone, inhibitor of DXS and fosmidomycin (inhibitor of deoxyxylulose 5-phosphate reductoisomerase (DXR, respectively. Young leaves of non-flowering plants were exposed to both inhibitors, adopting a non-invasive in vivo technique. Transcripts and proteins of DXS (3 isoforms, DXR, and hydroxymethylbutenyl diphosphate synthase (HDS were monitored, and protein stability was followed in isolated chloroplasts. Transcripts for DXS1 were repressed by both inhibitors, whereas transcripts for DXS2A&B, DXR and HDS increased after clomazone treatment but were barely affected by fosmidomycin treatment. DXS protein accumulated in response to both inhibitors, whereas DXR and HDS proteins were less affected. Fosmidomycin-induced accumulation of DXS protein indicated substantial posttranscriptional regulation. Furthermore, fosmidomycin effectively protected DXR against degradation in planta and in isolated chloroplasts. Thus our results suggest that DXR protein stability may be affected by substrate binding. In summary, the present results provide novel insight into the regulation of DXS expression in C. roseus in response to MEP-pathway perturbation.

  1. Enzyme Inhibitor Studies Reveal Complex Control of Methyl-D-Erythritol 4-Phosphate (MEP) Pathway Enzyme Expression in Catharanthus roseus

    Han, Mei; Heppel, Simon C.; Su, Tao; Bogs, Jochen; Zu, Yuangang; An, Zhigang; Rausch, Thomas

    2013-01-01

    In Catharanthus roseus, the monoterpene moiety exerts a strong flux control for monoterpene indole alkaloid (MIA) formation. Monoterpene synthesis depends on the methyl-D-erythritol 4-phosphate (MEP) pathway. Here, we have explored the regulation of this pathway in response to developmental and environmental cues and in response to specific enzyme inhibitors. For the MEP pathway entry enzyme 1-deoxy-D-xylulose 5-phosphate synthase (DXS), a new (type I) DXS isoform, CrDXS1, has been cloned, which, in contrast to previous reports on type II CrDXS, was not transcriptionally activated by the transcription factor ORCA3. Regulation of the MEP pathway in response to metabolic perturbations has been explored using the enzyme inhibitors clomazone (precursor of 5-ketochlomazone, inhibitor of DXS) and fosmidomycin (inhibitor of deoxyxylulose 5-phosphate reductoisomerase (DXR)), respectively. Young leaves of non-flowering plants were exposed to both inhibitors, adopting a non-invasive in vivo technique. Transcripts and proteins of DXS (3 isoforms), DXR, and hydroxymethylbutenyl diphosphate synthase (HDS) were monitored, and protein stability was followed in isolated chloroplasts. Transcripts for DXS1 were repressed by both inhibitors, whereas transcripts for DXS2A&B, DXR and HDS increased after clomazone treatment but were barely affected by fosmidomycin treatment. DXS protein accumulated in response to both inhibitors, whereas DXR and HDS proteins were less affected. Fosmidomycin-induced accumulation of DXS protein indicated substantial posttranscriptional regulation. Furthermore, fosmidomycin effectively protected DXR against degradation in planta and in isolated chloroplasts. Thus our results suggest that DXR protein stability may be affected by substrate binding. In summary, the present results provide novel insight into the regulation of DXS expression in C. roseus in response to MEP-pathway perturbation. PMID:23650515

  2. Characterization, biomedical and agricultural applications of protease inhibitors: A review.

    Shamsi, Tooba Naz; Parveen, Romana; Fatima, Sadaf

    2016-10-01

    This review describes Protease Inhibitors (PIs) which target or inhibit proteases, protein digesting enzymes. These proteases play a crucial task in many biological events including digestion, blood coagulation, apoptosis etc. Regardless of their crucial roles, they need to be checked regularly by PIs as their excess may possibly damage host organism. On basis of amino acid composition of PIs where Protease-PI enzymatic reactions occur i.e. serine, cysteine, and aspartic acid, they are classified. Nowadays, various PIs are being worked upon to fight various parasitic or viral diseases including malaria, schistosomiasis, colds, flu', dengue etc. They prevent an ongoing process begun by carcinogen exposure by keeping a check on metastasis. They also possess potential to reduce carcinogen-induced, increased levels of gene amplification to almost normal levels. Some PIs can principally be used for treatment of hypertension and congestive heart failure by blocking conversion of angiotensin I to angiotensin II for example Angiotensin-converting enzyme inhibitors (ACEIs). Also PIs target amyloid β-peptide (Aβ) level in brain which is prime responsible for development of Alzheimer's Disease (AD). Also, PIs inhibit enzymatic activity of HIV-1 Protease Receptor (PR) by preventing cleavage events in Gag and Gag-Pol that result in production of non-virulent virus particles. PMID:26955746

  3. RAMIPRIL IN THERAPY OF PATIENTS AFTER MYOCARDIAL INFARCTION

    I. V. Szirov; E. V. Malichenko

    2015-01-01

    Angiotensin converting enzyme inhibitors are the first line medicine for the treatment of the most of cardiovascular diseases. There is no class-effect for these drugs in myocardial infarction therapy. Moreover in myocardial infarction angiotensin converting enzyme inhibitors have significant intra-group differences. Ramipril is the one of the most studied drug of this group recommended for patients after acute myocardial infarction.

  4. Action of plant proteinase inhibitors on enzymes of physiopathological importance.

    Oliva, Maria Luiza V; Sampaio, Misako U

    2009-09-01

    Obtained from leguminous seeds, various plant proteins inhibit animal proteinases, including human, and can be considered for the development of compounds with biological activity. Inhibitors from the Bowman-Birk and plant Kunitz-type family have been characterized by proteinase specificity, primary structure and reactive site. Our group mostly studies the genus Bauhinia, mainly the species bauhinioides, rufa, ungulata and variegata. In some species, more than one inhibitor was characterized, exhibiting different properties. Although proteins from this group share high structural similarity, they present differences in proteinase inhibition, explored in studies using diverse biological models. PMID:19722028

  5. Improved Peak Capacity for Capillary Electrophoretic Separations of Enzyme Inhibitors with Activity-Based Detection Using Magnetic Bead Microreactors

    Yan, Xiaoyan; Gilman, S. Douglass

    2010-01-01

    A technique for separating and detecting enzyme inhibitors was developed using capillary electrophoresis with an enzyme microreactor. The on-column enzyme microreactor was constructed using NdFeB magnet(s) to immobilize alkaline phosphatase-coated superparamagnetic beads (2.8 μm diameter) inside a capillary before the detection window. Enzyme inhibition assays were performed by injecting a plug of inhibitor into a capillary filled with the substrate, AttoPhos. Product generated in the enzyme ...

  6. Structure-Based Inhibitor Design for an Enzyme That Binds Different Steriods

    Qiu,W.; Zhou, M.; Mazumdar, M.; Azzi, A.; Ghanmi, D.; Luu-The, V.; Labrie, F.; Lin, S.

    2007-01-01

    Human type 5 17{beta}-hydroxysteroid dehydrogenase plays a crucial role in local androgen formation in prostate tissue. Several chemicals were synthesized and tested for their ability to inhibit this enzyme, and a series of estradiol derivatives bearing a lactone on the D-ring were found to inhibit its activity efficiently. The crystal structure of the type 5 enzyme in complex with NADP and such a novel inhibitor, EM1404, was determined to a resolution of 1.30 {angstrom}. Significantly more hydrogen bonding and hydrophobic interactions were defined between EM1404 and the enzyme than in the substrate ternary complex. The lactone ring of EM1404 accounts for important interactions with the enzyme, whereas the amide group at the opposite end of the inhibitor contributes to the stability of three protein loops involved in the construction of the substrate binding site. EM1404 has a strong competitive inhibition, with a K{sub i} of 6.9 {+-} 1.4 nM, demonstrating 40 times higher affinity than that of the best inhibitor previously reported. This is observed despite the fact that the inhibitor occupies only part of the binding cavity. Attempts to soak the inhibitor into crystals of the binary complex with NADP were unsuccessful, yielding a structure with a polyethylene glycol fragment occupying the substrate binding site. The relative crystal packing is discussed. Combined studies of small molecule inhibitor synthesis, x-ray crystallography, enzyme inhibition, and molecular modeling make it possible to analyze the plasticity of the substrate binding site of the enzyme, which is essential for developing more potent and specific inhibitors for hormone-dependent cancer therapy.

  7. Binding of ACE-inhibitors to in vitro and patient-derived amyloid-β fibril models

    Bhavaraju, Manikanthan; Phillips, Malachi; Bowman, Deborah; Aceves-Hernandez, Juan M.; Hansmann, Ulrich H. E.

    2016-01-01

    Currently, no drugs exist that can prevent or reverse Alzheimer's disease, a neurodegenerative disease associated with the presence, in the brain, of plaques that are composed of β-amyloid (Aβ) peptides. Recent studies suggest that angiotensin-converting enzyme (ACE) inhibitors, a set of drugs used to treat hypertension, may inhibit amyloid formation in vitro. In the present study, we investigate through computer simulations the binding of ACE inhibitors to patient-derived Aβ fibrils and contrast it with that of ACE inhibitors binding to in vitro generated fibrils. The binding affinities of the ACE inhibitors are compared with that of Congo red, a dye that is used to identify amyloid structures and that is known to be a weak inhibitor of Aβ aggregation. We find that ACE inhibitors have a lower binding affinity to the patient-derived fibrils than to in vitro generated ones. For patient-derived fibrils, their binding affinities are even lower than that of Congo red. Our observations raise doubts on the hypothesis that these drugs inhibit fibril formation in Alzheimer patients by interacting directly with the amyloids.

  8. Inhibitors of Testosterone Biosynthetic and Metabolic Activation Enzymes

    Leping Ye

    2011-12-01

    Full Text Available The Leydig cells of the testis have the capacity to biosynthesize testosterone from cholesterol. Testosterone and its metabolically activated product dihydrotestosterone are critical for the development of male reproductive system and spermatogenesis. At least four steroidogenic enzymes are involved in testosterone biosynthesis: Cholesterol side chain cleavage enzyme (CYP11A1 for the conversion of cholesterol into pregnenolone within the mitochondria, 3β-hydroxysteroid dehydrogenase (HSD3B, for the conversion of pregnenolone into progesterone, 17α-hydroxylase/17,20-lyase (CYP17A1 for the conversion of progesterone into androstenedione and 17β-hydroxysteroid dehydrogenase (HSD17B3 for the formation of testosterone from androstenedione. Testosterone is also metabolically activated into more potent androgen dihydrotestosterone by two isoforms 5α-reductase 1 (SRD5A1 and 2 (SRD5A2 in Leydig cells and peripheral tissues. Many endocrine disruptors act as antiandrogens via directly inhibiting one or more enzymes for testosterone biosynthesis and metabolic activation. These chemicals include industrial materials (perfluoroalkyl compounds, phthalates, bisphenol A and benzophenone and pesticides/biocides (methoxychlor, organotins, 1,2-dibromo-3-chloropropane and prochloraz and plant constituents (genistein and gossypol. This paper reviews these endocrine disruptors targeting steroidogenic enzymes.

  9. Screening of marine actinobacteria for amylase enzymes inhibitors

    Raja, S.; Ganesan, S.; Sivakumar, K.; Thangaradjou, T.

    2010-01-01

    Amylase inhibitor producing actinobacteria were isolated and characterized from terrestrial environment and there is no much report found from marine environment, hence in the present study, 17 strains isolated from the rhizosphere sediments of mangroves were tested for their amylase inhibition ability. Seawater requirement test for the growth of actinobacteria found that the strains SSR-3, SSR-12 and SSR-16 requires at least 50% and SSR-6 requires at least 25% seawater for their growth. The ...

  10. Angiotensin converting enzyme inhibition patially prevents defecits in water maze performance, hippocampal synaptic plasticity and cerebral blood flow in streptozotocin-induced-diabetic rats

    Gispen, W.H.; Manschot, S.M.; Biessels, G.J.; Cameron, N.E.; Cotter, M.A.; Kamal, A.; Kappelle, L.J.

    2003-01-01

    Vascular dysfunction is important in the pathogenesis of peripheral complications of diabetes. However, the effects of diabetes on cerebral blood flow and the role of vascular deficits in the pathogenesis of diabetic encephalopathy are still unknown. The present study examined whether experimental d

  11. Association of Angiotensin Converting Enzyme I/D and α-actinin-3 R577X Genotypes with Growth Factors and Physical Fitness in Korean Children.

    Kim, Kijin; Ahn, Nayoung; Cheun, Wookwang; Byun, Jayoung; Joo, Youngsik

    2015-03-01

    This study analyzed the differences in aerobic and anaerobic exercise ability and growth-related indicators, depending on the polymorphism of the ACE and the ACTN3 genes, to understand the genetic influence of exercise ability in the growth process of children. The subjects of the study consisted of elementary school students (n=856, age 10.32±0.07 yr). The anthropometric parameters, physical fitness and growth factors were compared among groups of the ACE I/D or the ACTN3 R577X polymorphisms. There were no significant differences between the anthropometric parameters, physical fitness and growth factors for the ACE gene ID or the ACTN3 gene R577X polymorphism. However, the DD type of ACE gene was highest in the side step test (pACTN3 gene XX type significantly showed lower early bone age (pACTN3 R577X polymorphisms on the anthropometric parameters, physical fitness and growth factors of Korean children. However, the exercise experience and the DD type of the ACE gene may affect the early maturity of the bones. PMID:25729275

  12. Association of Angiotensin Converting Enzyme I/D and α-actinin-3 R577X Genotypes with Growth Factors and Physical Fitness in Korean Children

    Kim, Kijin; Ahn, Nayoung; Cheun, Wookwang; Byun, Jayoung; Joo, Youngsik

    2015-01-01

    This study analyzed the differences in aerobic and anaerobic exercise ability and growth-related indicators, depending on the polymorphism of the ACE and the ACTN3 genes, to understand the genetic influence of exercise ability in the growth process of children. The subjects of the study consisted of elementary school students (n=856, age 10.32±0.07 yr). The anthropometric parameters, physical fitness and growth factors were compared among groups of the ACE I/D or the ACTN3 R577X polymorphisms...

  13. High-Pressure-Assisted Enzymatic Release of Peptides and Phenolics Increases Angiotensin Converting Enzyme I Inhibitory and Antioxidant Activities of Pinto Bean Hydrolysates.

    Garcia-Mora, Patricia; Peñas, Elena; Frias, Juana; Zieliński, Henryk; Wiczkowski, Wiesław; Zielińska, Danuta; Martínez-Villaluenga, Cristina

    2016-03-01

    Pinto bean protein concentrate was hydrolyzed by subtilisins at 0.1, 100, and 200 MPa and 50 °C for 15 min. Alcalase hydrolysis at 100 MPa led to higher ACE inhibition, reducing power, and free radical scavenging activity of hydrolysates. However, hydrolysate obtained by Savinase at 200 MPa showed the best ACE-inhibitory and radical scavenging activities. Proteolysis by Savinase at 200 MPa was considered the most effective treatment to increase small peptides (benefits in the production of functional hydrolysates providing higher functionality and added value to the resulting hydrolysate due to synergistic effects of bioactive peptides and soluble phenolics. PMID:26857428

  14. Prevalence of angiotensin converting enzyme (ACE gene insertion/deletion polymorphism in South Indian population with hypertension and chronic kidney disease

    R Shanmuganathan

    2015-01-01

    Full Text Available Context: Chronic Kidney Disease (CKD is associated with a high risk of developing further severe complications such as, cardiovascular disease and eventually End Stage Renal Disease (ESRD leading to death. Hypertension plays a key role in the progression of renal failure and is also a chief risk factor for the occurrence of End Stage Renal Disease (ESRD. Aim: This study investigates the possible association of insertion (I and deletion (D polymorphism of ACE gene in patients of Chronic Kidney Disease (CKD with and without hypertension (HT. Settings and Design: Total 120 participants with 30 members in each group (Control, HT, CKD and CKD-HT were chosen followed by informed consent. Materials and Methods: Blood samples were collected and subjected to biochemical analyses and nested PCR amplification was performed to genotype the DNA, for ACE I/D using specific primers. Statistical Analysis: Statistical analyses were performed using SPSS version 13. Allele and genotypic frequency was calculated by direct gene counting method. Comparison of the different genotypes was done by using Chi square test. Odd′s ratios were calculated with a 95% confidence interval limit. Results: The ACE genotype were distributed as II, 27 (90%; DD, 2 (6.67% and ID, 1 (3.33% in control, II, 1 (3.33%; DD, 5 (16.67% and ID, 24 (80% in HT, II, 4 (13.33%; DD, 24 (80% and ID, 2 (6.67% in CKD and II, 0 (0%; DD, 2 (6.67% and ID, 28 (93.33% in CKD-HT group. Conclusions: D allele of ACE gene confers a greater role in genetic variations underlying CKD and hypertension. This result suggest that CKD patients should be offered analysis for defects in ACE I/D polymorphisms, especially if they are hypertensive.

  15. Relationship between Angiotensin-Converting Enzyme Insertion/Deletion Gene Polymorphism and Susceptibility of Minimal Change Nephrotic Syndrome: A Meta-Analysis

    Tian-Biao Zhou

    2011-01-01

    Africans: D: =.81, DD: =.49. Furthermore, the II genotype seemed not to play a protective role against MCNS risk for Asians, Caucasians and Africans (=.12, =.09, =.76, resp.. Interestingly, there was also significant association between ACE I/D gene polymorphism and MCNS susceptibility in overall populations (D: =.007, DD: =.04, II: =.03. Conclusion. D allele or DD genotype might be a significant genetic molecular marker for MCNS susceptibility in Asians and overall populations, but not for Caucasians and Africans. More larger and rigorous genetic epidemiological investigations are required to further explore this association.

  16. The angiotensin-converting enzyme (ACE) gene insertion/ deletion dimorphism tracks with higher serum ace activities in both younger and older subjects

    The absence of a 287 base pair alu sequence in the ACE gene (D allele) is associated with higher ACE levels than its presence (I allele) in adults. We carried out a case control study of thr ACE*I/D dimorphism in relation to circulating ACE activities to evaluate associations between the two variables in adults, compared to younger (18 years or less) individuals. Genotypes of the ACE*I/D dimorphism were determined on DNA samples from a population of 164 random (unrelated) Emirtaes nationals, composed of groups: 112 subjects above 18 years of age (range=20-77), and 52 subjects of 18 years or less (range=1-18) and analyzed for putative associations with serum ACE activities. ACE*I/D genotypes of the 164 individualds were determined by assays based on polymerase chain reaction. ACE activities were determined on serum samples of these subjects bu colorimetric assays. The D allele was associared with increasd ACE values in both adult and younger individuals. Mean ACE activity levels associated with II, ID and DD genotypes, however, were 42%-61% higher in the 18 years and under group of subjects. The ACE*I/D marker accounted for 28% of the variance of the phenomenon determining ACE levels in adults, and for 30% among youngsters. The ACE*I/D dimorphism is correlated strongly with circulating ACE activities in both and young Emirati, subjects and the corresponding mean ACE activities were significantly higher among the youngsters. (author)

  17. Plant-Derived Substances and Cardiovascular Diseases : Effects of Flavonoids, Terpenes and Sterols on Angiotensin-Converting Enzyme and Nitric Oxide

    Persson, Ingrid

    2009-01-01

    Diet has for many years been known to play a key role in the development of chronic diseases. There are clear associations between consumption of vegetables, fruits and berries, and risk of cardiovascular diseases, the number one cause of death in the world. To maintain homeostasis of the vascular wall the balance between angiotensin II, nitric oxide and reactive oxygen species is of great importance in order to affect the development of cardiovascular diseases. Angiotensin II, a potent vasoc...

  18. Angiotensin I-Converting Enzyme Inhibitor Activity on Egg Albumen Fermentation

    Nahariah, N.; A M Legowo; Abustam, E.; Hintono, A.

    2015-01-01

    Lactobacillus plantarum is used for fermentation of fish products, meat and milk. However, the utilization of these bacteria in egg processing has not been done. This study was designed to evaluate the potential of fermented egg albumen as a functional food that is rich in angiotensin I-converting enzyme inhibitors activity (ACE-inhibitor activity) and is antihypertensive. A completely randomized design was used in this study with six durations of fermentation (6, 12, 18, 24, 30, and 36 h) as...

  19. Action of plant proteinase inhibitors on enzymes of physiopathological importance

    Maria Luiza V. Oliva

    2009-09-01

    Full Text Available Obtained from leguminous seeds, various plant proteins inhibit animal proteinases, including human, and can be considered for the development of compounds with biological activity. Inhibitors from the Bowman-Birk and plant Kunitz-type family have been characterized by proteinase specificity, primary structure and reactive site. Our group mostly studies the genus Bauhinia, mainly the species bauhinioides, rufa, ungulata and variegata. In some species, more than one inhibitor was characterized, exhibiting different properties. Although proteins from this group share high structural similarity, they present differences in proteinase inhibition, explored in studies using diverse biological models.Obtidas de sementes leguminosas, várias proteínas inibem proteinases de origem animal, incluindo humanas, e podem ser consideradas para o desenvolvimento de compostos com atividade biológica. Inibidores da família Bowman-Birk e da família Kunitz vegetal tem sido caracterizados em relação a especificidade para proteinase, estrutura primária e sitio reativo. O nosso grupo majoritariamente vem estudando o gênero Bauhinia, principalmente as espécies bauhinioides, rufa, ungulatae variegata. Em algumas espécies, mais de um inibidor com propriedades diferentes foi caracterizado. Embora tais proteínas apresentem alta similaridade estrutural, diferem quanto à inibição de proteinases, e foram exploradas em estudos utilizando diversos modelos biológicos.

  20. A theoretical study of the molecular mechanism of the GAPDH Trypanosoma cruzi enzyme involving iodoacetate inhibitor

    Carneiro, Agnaldo Silva; Lameira, Jerônimo; Alves, Cláudio Nahum

    2011-10-01

    The glyceraldehyde-3-phosphate dehydrogenase enzyme (GAPDH) is an important biological target for the development of new chemotherapeutic agents against Chagas disease. In this Letter, the inhibition mechanism of GAPDH involving iodoacetate (IAA) inhibitor was studied using the hybrid quantum mechanical/molecular mechanical (QM/MM) approach and molecular dynamic simulations. Analysis of the potential energy surface and potential of mean force show that the covalent attachment of IAA inhibitor to the active site of the enzyme occurs as a concerted process. In addition, the energy terms decomposition shows that NAD+ plays an important role in stabilization of the reagents and transition state.

  1. Structural Characterization of Inhibitors with Selectivity against Members of a Homologous Enzyme Family

    Pavlovsky, Alexander G.; Liu, Xuying; Faehnle, Christopher R.; Potente, Nina; Viola, Ronald E. (Toledo)

    2013-01-31

    The aspartate biosynthetic pathway provides essential metabolites for many important biological functions, including the production of four essential amino acids. As this critical pathway is only present in plants and microbes, any disruptions will be fatal to these organisms. An early pathway enzyme, L-aspartate-{beta}-semialdehyde dehydrogenase, produces a key intermediate at the first branch point of this pathway. Developing potent and selective inhibitors against several orthologs in the L-aspartate-{beta}-semialdehyde dehydrogenase family can serve as lead compounds for antibiotic development. Kinetic studies of two small molecule fragment libraries have identified inhibitors that show good selectivity against L-aspartate-{beta}-semialdehyde dehydrogenases from two different bacterial species, Streptococcus pneumoniae and Vibrio cholerae, despite the presence of an identical constellation of active site amino acids in this homologous enzyme family. Structural characterization of enzyme-inhibitor complexes have elucidated different modes of binding between these structurally related enzymes. This information provides the basis for a structure-guided approach to the development of more potent and more selective inhibitors.

  2. Structural characterization of inhibitors with selectivity against members of a homologous enzyme family.

    Pavlovsky, Alexander G; Liu, Xuying; Faehnle, Christopher R; Potente, Nina; Viola, Ronald E

    2012-01-01

    The aspartate biosynthetic pathway provides essential metabolites for many important biological functions, including the production of four essential amino acids. As this critical pathway is only present in plants and microbes, any disruptions will be fatal to these organisms. An early pathway enzyme, l-aspartate-β-semialdehyde dehydrogenase, produces a key intermediate at the first branch point of this pathway. Developing potent and selective inhibitors against several orthologs in the l-aspartate-β-semialdehyde dehydrogenase family can serve as lead compounds for antibiotic development. Kinetic studies of two small molecule fragment libraries have identified inhibitors that show good selectivity against l-aspartate-β-semialdehyde dehydrogenases from two different bacterial species, Streptococcus pneumoniae and Vibrio cholerae, despite the presence of an identical constellation of active site amino acids in this homologous enzyme family. Structural characterization of enzyme-inhibitor complexes have elucidated different modes of binding between these structurally related enzymes. This information provides the basis for a structure-guided approach to the development of more potent and more selective inhibitors. PMID:22039970

  3. A Trypsin Inhibitor from Clitoria fairchildiana Cotyledons is Active Against Digestive Enzymes of Aedes aegypti Larvae.

    de Oliveira, Lucilene O; Fernandes, Kátia V S; Pádua, Dayanni de Souza; Carvalho, André de O; Lemos, Francisco J A; Gomes, Valdirene M; Oliveira, Antônia E A; Ferreira, André T da Silva; Perales, Jonas

    2015-01-01

    Aedes aegypti, the principal mosquito vector of yellow fever, dengue fever and chikungunya fever virus-transmitted diseases, is an insect closely associated with humans and their housing habitats. As there is no commercially available vaccine, prevention is the most suggested form of avoiding disease spreading and a number of studies are being developed in order to give support to vector control operations. The present study reports on the identification of a trypsin inhibitor isolated from cotyledons of the Clitoria fairchildiana amazonic tree seeds, which was able to reduce by 87.93 % the activity of digestive enzymes of fourth instar A. aegypti larva. A partial amino acid sequence showed strong similarity with sequences from several trypsin inhibitors already reported in the literature. The 13,000 Da isolated inhibitor was seen to be active solely against trypsin-like enzymes, neither acting on papain, α-amylase nor on other serine proteases, such as elastase, chymotrypsin or subtilisin. At least six from seven active digestive proteases from A. aegypti larvae, visualized by zymography, were severely affected soon after exposed to the inhibitor. The strong and specific action of the isolated inhibitor against trypsin digestive enzymes of this insect vector led us to believe that this protein may be a good candidate for a prospective alternative biocontrol method. PMID:26156641

  4. Polymorphism of angiotensin I/D-converting enzyme gene in the Chinese people%中国人血管紧张素转换酶基因I/D多态性的研究

    王育平; 刘国树

    2005-01-01

    目的 :探讨中国人血管紧张素转换酶( angiotensin converting enzyme, ACE)基因多态性分布. 方法:利用聚合酶链反应( polymerase chain reaction, PCR)方法检测 141例正常人和 200例高血压患者的 ACE基因型 ,同时检测其血清 ACE水平,并对 55例未服用过降压药物的高血压患者分别于治疗前及口服卡托普利 25 mg 1 h后测定其血清 ACE活性的变化. 结果:高血压组的 I等位基因频率( 0.65)显著高于正常对照组( 0.57) (P< 0.05). DD型患者 ACE活性最高,临床合并症多,预后差.未发现基因型与血管紧张素转换酶抑制剂( angiotensin converting enzyme inhibitor,ACEI)疗效有关. 结论:① ACEI等位基因可能为中国人原发性高血压的危险因子.② ACE基因缺失多态性与血清 ACE活性有关,并增加高血压合并靶器官损害的危险.③ ACE基因多态性与 ACEI疗效无关.

  5. Activity-based chemical proteomics accelerates inhibitor development for deubiquitylating enzymes.

    Altun, Mikael; Kramer, Holger B; Willems, Lianne I; McDermott, Jeffrey L; Leach, Craig A; Goldenberg, Seth J; Kumar, K G Suresh; Konietzny, Rebecca; Fischer, Roman; Kogan, Edward; Mackeen, Mukram M; McGouran, Joanna; Khoronenkova, Svetlana V; Parsons, Jason L; Dianov, Grigory L; Nicholson, Benjamin; Kessler, Benedikt M

    2011-11-23

    Converting lead compounds into drug candidates is a crucial step in drug development, requiring early assessment of potency, selectivity, and off-target effects. We have utilized activity-based chemical proteomics to determine the potency and selectivity of deubiquitylating enzyme (DUB) inhibitors in cell culture models. Importantly, we characterized the small molecule PR-619 as a broad-range DUB inhibitor, and P22077 as a USP7 inhibitor with potential for further development as a chemotherapeutic agent in cancer therapy. A striking accumulation of polyubiquitylated proteins was observed after both selective and general inhibition of cellular DUB activity without direct impairment of proteasomal proteolysis. The repertoire of ubiquitylated substrates was analyzed by tandem mass spectrometry, identifying distinct subsets for general or specific inhibition of DUBs. This enabled identification of previously unknown functional links between USP7 and enzymes involved in DNA repair. PMID:22118674

  6. Insights on Cytochrome P450 Enzymes and Inhibitors Obtained Through QSAR Studies

    Maryam Foroozesh

    2012-08-01

    Full Text Available The cytochrome P450 (CYP superfamily of heme enzymes play an important role in the metabolism of a large number of endogenous and exogenous compounds, including most of the drugs currently on the market. Inhibitors of CYP enzymes have important roles in the treatment of several disease conditions such as numerous cancers and fungal infections in addition to their critical role in drug-drug interactions. Structure activity relationships (SAR, and three-dimensional quantitative structure activity relationships (3D-QSAR represent important tools in understanding the interactions of the inhibitors with the active sites of the CYP enzymes. A comprehensive account of the QSAR studies on the major human CYPs 1A1, 1A2, 1B1, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4 and a few other CYPs are detailed in this review which will provide us with an insight into the individual/common characteristics of the active sites of these enzymes and the enzyme-inhibitor interactions.

  7. 21 CFR 343.80 - Professional labeling.

    2010-04-01

    ... bleeding time. Drug Interactions Angiotensin Converting Enzyme (ACE) Inhibitors: The hyponatremic and hypotensive effects of ACE inhibitors may be diminished by the concomitant administration of aspirin due to... inhibitor of both prostaglandin synthesis and platelet aggregation than other salicylic acid...

  8. ADMET, Docking studies & binding energy calculations of some Novel ACE - inhibitors for the treatment of Diabetic Nephropathy

    Gade Deepak Reddy

    2012-09-01

    Full Text Available Diabetic Nephropathy (DN is one of the major complications of diabetes mellitus, representing the leading of cause of chronic renal disease and a major cause of morbidity and mortality in both type 1 and type 2 diabetic patients. The Renin-Angiotensin-Aldosterone System (RAAS has been implicated in the pathophysiology of DN, and suggests a therapeutic target for blocking this system. Therefore, inhibition of RAAS plays a crucial role in the treatment of DN and therapeutic intervention mostly involves administration of angiotensin converting enzyme (ACE inhibitors and angiotensin AT1 receptor blockers. In this current study, we have used computational methods to design 37 novel ACE-inhibitors and evaluated them for the interaction with the enzyme ACE through insilico analysis. The obtained results were compared with the standard drug enalapril to find out the potential inhibitors. Here we report that ligand 4 exhibited strongest inhibitory activity among all. All the analogs are also screened for their ADME & Toxicity profiles using insilico tools and ligand 9 is having better binding affinity next to ligand 4, and also having better ADMET profile when compared to that of ligand 4. Post docking calculations were also performed for the docked complexes in order to identify the individual ligand binding energies by employing Multi-Ligand Bimolecular Association with Energetics (Embrace

  9. Inhibitors of the Hydrolytic Enzyme Dimethylarginine Dimethylaminohydrolase (DDAH): Discovery, Synthesis and Development.

    Murphy, Rhys B; Tommasi, Sara; Lewis, Benjamin C; Mangoni, Arduino A

    2016-01-01

    Dimethylarginine dimethylaminohydrolase (DDAH) is a highly conserved hydrolytic enzyme found in numerous species, including bacteria, rodents, and humans. In humans, the DDAH-1 isoform is known to metabolize endogenous asymmetric dimethylarginine (ADMA) and monomethyl arginine (l-NMMA), with ADMA proposed to be a putative marker of cardiovascular disease. Current literature reports identify the DDAH family of enzymes as a potential therapeutic target in the regulation of nitric oxide (NO) production, mediated via its biochemical interaction with the nitric oxide synthase (NOS) family of enzymes. Increased DDAH expression and NO production have been linked to multiple pathological conditions, specifically, cancer, neurodegenerative disorders, and septic shock. As such, the discovery, chemical synthesis, and development of DDAH inhibitors as potential drug candidates represent a growing field of interest. This review article summarizes the current knowledge on DDAH inhibition and the derived pharmacokinetic parameters of the main DDAH inhibitors reported in the literature. Furthermore, current methods of development and chemical synthetic pathways are discussed. PMID:27187323

  10. Na(+)-H(+) exchanger inhibitor prevents early death in hereditary cardiomyopathy.

    Bkaily, Ghassan; Chahine, Mirna; Al-Khoury, Johny; Avedanian, Levon; Beier, Norbert; Scholz, Wolfgang; Jacques, Danielle

    2015-11-01

    Using the UM-X7.1 hereditary cardiomyopathic and muscular dystrophy hamsters (HCMH), we tested the effects of lifelong preventive or curative treatments during the heart failure phase with the NHE-1 inhibitor EMD 87580 (EMD) or with the angiotensin-converting enzyme inhibitor cilazapril on the intracellular Na(+) and Ca(2+) overloads, elevated level of NHE-1, necrosis, hypertrophy, heart failure, and early death. Our results showed that 310-day pretreatment of 30-day-old HCMHs with EMD significantly prevented cardiac necrosis, cardiomyocyte hypertrophy, and reduced the heart to body mass ratio. This treatment significantly prevented Na(+) and Ca(2+) overloads and the increase in NHE-1 protein level observed in HCMHs. Importantly, this lifelong preventive treatment significantly decreased the levels of creatine kinase and prevented early death of HCMHs. Curative treatment of hypertrophic 275-day-old HCMHs for 85 days with EMD significantly prevented hypertrophy and early death of HCMHs. However, treatments with cilazapril did not have any significant effects on the cardiac parameters studied or on early death of HCMHs. Our results suggest that the increase in the NHE-1 level and the consequent Na(+) and Ca(2+) overloads are implicated in the pathological process leading to heart failure and early death in HCMHs, and treatment with the NHE-1 inhibitor is promising for preventing early death in hereditary cardiomyopathy. PMID:26291649

  11. Polysulfide compounds as inhibitors of the key base excision repair enzymes

    Salakhutdinov N. F.

    2012-06-01

    Full Text Available Aim. To increase the capacity of antitumor therapy based on DNA damage it is important to minimize the repair of DNA lesions that can be achieved by inhibiting the activity of key DNA repair enzymes. To this end several benzopentathiepine and benzo[1,3]dithiol derivatives were synthesized and tested as inhibitors of the key base excision repair (BER enzymes, PARP1, DNA polymerase β, and APE1. Methods. The procedure of synthesis of several new compounds was developed. The inhibitory capacity of the compounds was estimated by comparison of the enzyme activities in specific tests in the presence of compounds versus their absence. Results. Benzopentathiepine derivative bearing trifluoromethyl group at the 1st position was shown to be a weak inhibitor of PARP1. Cyclic substituents at the 1st position attached through amide bond bring about moderate enhancement of pol β inhibition. Each studied substituent at the 1st position considerably increases the inhibition of APE1-catalyzed hydrolysis of AP sites as compared to parent compound. Conclusions. Several new inhibitors of BER enzymes were revealed. The directions for further modification of compounds to improve their inhibitory activity were found out.

  12. Retrostatin, a new specific enzyme inhibitor against avian myeloblastosis virus reverse transcriptase.

    Nishio, M; Kuroda, A; Suzuki, M; Ishimaru, K; Nakamura, S; Nomi, R

    1983-07-01

    A novel enzyme inhibitor against RNA-directed DNA polymerase of avian myeloblastosis virus was produced by an isolate of a new streptomycete for which the name Streptomyces retrostaticus is proposed. This enzyme inhibitor, which was named retrostatin, did not inhibit DNA-directed DNA polymerase of Escherichia coli and DNA-directed RNA polymerase of Ehrlich ascites tumor cells. Retrostatin was produced by the microorganism together with streptonigrin. These two substances were extracted from the culture broth with ethyl acetate at acidic pH. Retrostatin is an acidic pH indicator and the free acid was recovered as a red powder. Retrostatin had weak antibiotic activities against Gram-positive bacteria and yeasts. PMID:6193091

  13. Mutational analysis of a type II topoisomerase cleavage site: distinct requirements for enzyme and inhibitors.

    Freudenreich, C H; Kreuzer, K. N.

    1993-01-01

    We have analyzed the DNA sequence requirements for cleavage of a 30 bp oligonucleotide that contains a strong bacteriophage T4 type II topoisomerase site. A novel method was used to generate substrates with each of the four nucleotides at 10 positions surrounding the cleavage site, and mutant substrates were also prepared for the four internal positions of the staggered cleavage site. The substrates were tested for cleavage in the presence of several inhibitors that induce enzyme-mediated cle...

  14. What Is the True Structure of D609, a Widely Used Lipid Related Enzyme Inhibitor?

    Kato, Mikako; Hammam, Mostafa A S; Taniguchi, Tohru; Suga, Yoshiko; Monde, Kenji

    2016-02-19

    D609 (1) has been used as a lipid-related enzyme inhibitor during the past three decades. Although it has eight possible stereoisomers, no systematic research considering its chirality has been performed. In this paper, eight possible chiral alcohols as direct precursors of D609 were synthesized, and their stereochemistries were elucidated by a vibrational circular dichroism (VCD) technique. Phosphatidylcholine-specific phospholipase C and sphingomyelin synthase inhibition assays of these isomers showed considerable differences in their activities. PMID:26854352

  15. Structural Characterization of Inhibitors with Selectivity against Members of a Homologous Enzyme Family

    Pavlovsky, Alexander G.; Liu, Xuying; Faehnle, Christopher R.; Potente, Nina; Ronald E. Viola

    2011-01-01

    The aspartate biosynthetic pathway provides essential metabolites for many important biological functions, including the production of four essential amino acids. Since this critical pathway is only present in plants and microbes any disruptions will be fatal to these organisms. An early pathway enzyme, L-aspartate-β-semialdehyde dehydrogenase (ASADH), produces a key intermediate at the first branch point of this pathway. Developing potent and selective inhibitors against several orthologs in...

  16. Angiotensin-I-Converting Enzyme (ACE Inhibitors from Marine Resources: Prospects in the Pharmaceutical Industry

    Isuru Wijesekara

    2010-03-01

    Full Text Available Hypertension or high blood pressure is one of the major independent risk factors for cardiovascular diseases. Angiotensin-I-converting enzyme (EC 3.4.15.1; ACE plays an important physiological role in regulation of blood pressure by converting angiotensin I to angiotensin II, a potent vasoconstrictor. Therefore, the inhibition of ACE activity is a major target in the prevention of hypertension. Recently, the search for natural ACE inhibitors as alternatives to synthetic drugs is of great interest to prevent several side effects and a number of novel compounds such as bioactive peptides, chitooligosaccharide derivatives (COS and phlorotannins have been derived from marine organisms as potential ACE inhibitors. These inhibitory derivatives can be developed as nutraceuticals and pharmaceuticals with potential to prevent hypertension. Hence, the aim of this review is to discuss the marine-derived ACE inhibitors and their future prospects as novel therapeutic drug candidates for treat hypertension.

  17. Sequence diversity of NanA manifests in distinct enzyme kinetics and inhibitor susceptibility

    Xu, Zhongli; von Grafenstein, Susanne; Walther, Elisabeth; Fuchs, Julian E.; Liedl, Klaus R.; Sauerbrei, Andreas; Schmidtke, Michaela

    2016-04-01

    Streptococcus pneumoniae is the leading pathogen causing bacterial pneumonia and meningitis. Its surface-associated virulence factor neuraminidase A (NanA) promotes the bacterial colonization by removing the terminal sialyl residues from glycoconjugates on eukaryotic cell surface. The predominant role of NanA in the pathogenesis of pneumococci renders it an attractive target for therapeutic intervention. Despite the highly conserved activity of NanA, our alignment of the 11 NanAs revealed the evolutionary diversity of this enzyme. The amino acid substitutions we identified, particularly those in the lectin domain and in the insertion domain next to the catalytic centre triggered our special interest. We synthesised the representative NanAs and the mutagenized derivatives from E. coli for enzyme kinetics study and neuraminidase inhibitor susceptibility test. Via molecular docking we got a deeper insight into the differences between the two major variants of NanA and their influence on the ligand-target interactions. In addition, our molecular dynamics simulations revealed a prominent intrinsic flexibility of the linker between the active site and the insertion domain, which influences the inhibitor binding. Our findings for the first time associated the primary sequence diversity of NanA with the biochemical properties of the enzyme and with the inhibitory efficiency of neuraminidase inhibitors.

  18. Chalcone-based Selective Inhibitors of a C4 Plant Key Enzyme as Novel Potential Herbicides

    Nguyen, G. T. T.; Erlenkamp, G.; Jäck, O.; Küberl, A.; Bott, M.; Fiorani, F.; Gohlke, H.; Groth, G.

    2016-06-01

    Weeds are a challenge for global food production due to their rapidly evolving resistance against herbicides. We have identified chalcones as selective inhibitors of phosphoenolpyruvate carboxylase (PEPC), a key enzyme for carbon fixation and biomass increase in the C4 photosynthetic pathway of many of the world’s most damaging weeds. In contrast, many of the most important crop plants use C3 photosynthesis. Here, we show that 2‧,3‧,4‧,3,4-Pentahydroxychalcone (IC50 = 600 nM) and 2‧,3‧,4‧-Trihydroxychalcone (IC50 = 4.2 μM) are potent inhibitors of C4 PEPC but do not affect C3 PEPC at a same concentration range (selectivity factor: 15–45). Binding and modeling studies indicate that the active compounds bind at the same site as malate/aspartate, the natural feedback inhibitors of the C4 pathway. At the whole plant level, both substances showed pronounced growth-inhibitory effects on the C4 weed Amaranthus retroflexus, while there were no measurable effects on oilseed rape, a C3 plant. Growth of selected soil bacteria was not affected by these substances. Our chalcone compounds are the most potent and selective C4 PEPC inhibitors known to date. They offer a novel approach to combat C4 weeds based on a hitherto unexplored mode of allosteric inhibition of a C4 plant key enzyme.

  19. Designed Inhibitors of Insulin-Degrading Enzyme Regulate the Catabolism and Activity of Insulin

    Leissring, Malcolm A.; Malito, Enrico; Hedouin, Sabrine; Reinstatler, Lael; Sahara, Tomoko; Abdul-Hay, Samer O.; Choudhry, Shakeel; Maharvi, Ghulam M.; Fauq, Abdul H.; Huzarska, Malwina; May, Philip S.; Choi, Sungwoon; Logan, Todd P.; Turk, Benjamin E.; Cantley, Lewis C.; Manolopoulou, Marika; Tang, Wei-Jen; Stein, Ross L.; Cuny, Gregory D.; Selkoe, Dennis J. (Harvard-Med); (BWH); (Yale-MED); (Scripps); (UC); (Mayo)

    2010-09-20

    Insulin is a vital peptide hormone that is a central regulator of glucose homeostasis, and impairments in insulin signaling cause diabetes mellitus. In principle, it should be possible to enhance the activity of insulin by inhibiting its catabolism, which is mediated primarily by insulin-degrading enzyme (IDE), a structurally and evolutionarily distinctive zinc-metalloprotease. Despite interest in pharmacological inhibition of IDE as an attractive anti-diabetic approach dating to the 1950s, potent and selective inhibitors of IDE have not yet emerged. We used a rational design approach based on analysis of combinatorial peptide mixtures and focused compound libraries to develop novel peptide hydroxamic acid inhibitors of IDE. The resulting compounds are {approx} 10{sup 6} times more potent than existing inhibitors, non-toxic, and surprisingly selective for IDE vis-a-vis conventional zinc-metalloproteases. Crystallographic analysis of an IDE-inhibitor complex reveals a novel mode of inhibition based on stabilization of IDE's 'closed,' inactive conformation. We show further that pharmacological inhibition of IDE potentiates insulin signaling by a mechanism involving reduced catabolism of internalized insulin. Conclusions/Significance: The inhibitors we describe are the first to potently and selectively inhibit IDE or indeed any member of this atypical zinc-metalloprotease superfamily. The distinctive structure of IDE's active site, and the mode of action of our inhibitors, suggests that it may be possible to develop inhibitors that cross-react minimally with conventional zinc-metalloproteases. Significantly, our results reveal that insulin signaling is normally regulated by IDE activity not only extracellularly but also within cells, supporting the longstanding view that IDE inhibitors could hold therapeutic value for the treatment of diabetes.

  20. Fumarate analogs act as allosteric inhibitors of the human mitochondrial NAD(P+-dependent malic enzyme.

    Ju-Yi Hsieh

    Full Text Available Human mitochondrial NAD(P+-dependent malic enzyme (m-NAD(P-ME is allosterically activated by the four-carbon trans dicarboxylic acid, fumarate. Previous studies have suggested that the dicarboxylic acid in a trans conformation around the carbon-carbon double bond is required for the allosteric activation of the enzyme. In this paper, the allosteric effects of fumarate analogs on m-NAD(P-ME are investigated. Two fumarate-insensitive mutants, m-NAD(P-ME_R67A/R91A and m-NAD(P-ME_K57S/E59N/K73E/D102S, as well as c-NADP-ME, were used as the negative controls. Among these analogs, mesaconate, trans-aconitate, monomethyl fumarate and monoethyl fumarate were allosteric activators of the enzyme, while oxaloacetate, diethyl oxalacetate, and dimethyl fumarate were found to be allosteric inhibitors of human m-NAD(P-ME. The IC50 value for diethyl oxalacetate was approximately 2.5 mM. This paper suggests that the allosteric inhibitors may impede the conformational change from open form to closed form and therefore inhibit m-NAD(P-ME enzyme activity.

  1. Biosensors based on enzyme field-effect transistors for determination of some substrates and inhibitors.

    Dzyadevych, Sergei V; Soldatkin, Alexey P; Korpan, Yaroslav I; Arkhypova, Valentyna N; El'skaya, Anna V; Chovelon, Jean-Marc; Martelet, Claude; Jaffrezic-Renault, Nicole

    2003-10-01

    This paper is a review of the authors' publications concerning the development of biosensors based on enzyme field-effect transistors (ENFETs) for direct substrates or inhibitors analysis. Such biosensors were designed by using immobilised enzymes and ion-selective field-effect transistors (ISFETs). Highly specific, sensitive, simple, fast and cheap determination of different substances renders them as promising tools in medicine, biotechnology, environmental control, agriculture and the food industry. The biosensors based on ENFETs and direct enzyme analysis for determination of concentrations of different substrates (glucose, urea, penicillin, formaldehyde, creatinine, etc.) have been developed and their laboratory prototypes were fabricated. Improvement of the analytical characteristics of such biosensors may be achieved by using a differential mode of measurement, working solutions with different buffer concentrations and specific agents, negatively or positively charged additional membranes, or genetically modified enzymes. These approaches allow one to decrease the effect of the buffer capacity influence on the sensor response in an aim to increase the sensitivity of the biosensors and to extend their dynamic ranges. Biosensors for the determination of concentrations of different toxic substances (organophosphorous pesticides, heavy metal ions, hypochlorite, glycoalkaloids, etc.) were designed on the basis of reversible and/or irreversible enzyme inhibition effect(s). The conception of an enzymatic multibiosensor for the determination of different toxic substances based on the enzyme inhibition effect is also described. We will discuss the respective advantages and disadvantages of biosensors based on the ENFETs developed and also demonstrate their practical application. PMID:12904953

  2. Acetylcholinesterase capillary enzyme reactor for screening and characterization of selective inhibitors.

    da Silva, Joyce Izidoro; de Moraes, Marcela Cristina; Vieira, Lucas Campos Curcino; Corrêa, Arlene Gonçalves; Cass, Quezia Bezerra; Cardoso, Carmen Lucia

    2013-01-25

    The aim of the present work is to report on the optimized preparation of capillary enzyme reactors (ICERs) based on acetylcholinesterase (AChE, EC 3.1.1.7), for the screening of selective inhibitors. The AChE-ICERs were prepared by using the homobifunctional linker glutaraldehyde through Schiff base linkage. The enzyme was anchored onto a modified fused silica capillary and employed as an LC biochromatography column for online studies, with UV-vis detection. Not only did the tailored AChE-ICER result in maintenance of the activity of the immobilized enzyme, but it also significantly improved the stability of the enzyme in the presence of organic solvents. In addition, the kinetic studies demonstrated that the enzyme retained its activity with high stability, preserving its initial activity over 10months. The absence of non-specific matrix interactions, immediate recovery of the enzymatic activity, and short analysis time were the main advantages of this AChE-ICER. The use of AChE-ICER in the ligands recognition assay was validated by evaluation of four known reversible inhibitors (galanthamine, tacrine, propidium, and rivastigmine), and the same order of inhibitory potencies described in the literature was found. The immobilized enzyme was utilized in the screening of 21 coumarin derivatives. In this library, two new potent inhibitors were identified: coumarins 20 (IC(50) 17.14±3.50μM) and 21 (IC(50) 6.35±1.20μM), which were compared to the standard galanthamine (IC(50) 12.68±2.40μM). Considering the high inhibitory activities of these compounds, with respect to the AChE-ICER, the mechanism of action was investigated. Both coumarins 20 and 21 exhibited a competitive mechanism of action, furnishing K(i) values of 8.04±0.18 and 2.67±0.18μM, respectively. The results revealed that the AChE-ICER developed herein represents a useful tool for the biological screening of inhibitor candidates and evaluation of action mechanism. PMID:22391555

  3. Ramipril

    ... a class of medications called angiotensin-converting enzyme (ACE) inhibitors. It works by decreasing certain chemicals that tighten ... pharmacist if you are allergic to ramipril; other ACE inhibitors such as benazepril (Lotensin, in Lotrel), captopril (Capoten), ...

  4. Captopril

    ... a class of medications called angiotensin-converting enzyme (ACE) inhibitors. It decreases certain chemicals that tighten the blood ... pharmacist if you are allergic to captopril; other ACE inhibitors such as benazepril (Lotensin, in Lotrel), captopril (Capoten), ...

  5. Benazepril

    ... a class of medications called angiotensin-converting enzyme (ACE) inhibitors. It works by decreasing certain chemicals that tighten ... pharmacist if you are allergic to benazepril; other ACE inhibitors such as captopril (Capoten), enalapril (Vasotec, in Vaseretic), ...

  6. Trandolapril

    ... a class of medications called angiotensin-converting enzyme (ACE) inhibitors. It works by decreasing certain chemicals that tighten ... pharmacist if you are allergic to trandolapril; other ACE inhibitors such as benazepril (Lotensin, in Lotrel), captopril (Capoten), ...

  7. Lisinopril

    ... a class of medications called angiotensin-converting enzyme (ACE) inhibitors. It works by decreasing certain chemicals that tighten ... pharmacist if you are allergic to lisinopril; other ACE inhibitors such as enalapril (Vasotec, in Vaseretic), benazepril (Lotensin, ...

  8. Fosinopril

    ... a class of medications called angiotensin-converting enzyme (ACE) inhibitors. It works by decreasing certain chemicals that tighten ... pharmacist if you are allergic to fosinopril; other ACE inhibitors such as benazepril (Lotensin, in Lotrel), captopril (Capoten), ...

  9. Enalapril

    ... a class of medications called angiotensin-converting enzyme (ACE) inhibitors. It works by decreasing certain chemicals that tighten ... pharmacist if you are allergic to enalapril; other ACE inhibitors such as benazepril (Lotensin, in Lotrel), captopril (Capoten), ...

  10. Quinapril

    ... a class of medications called angiotensin-converting enzyme (ACE) inhibitors. It works by decreasing certain chemicals that tighten ... pharmacist if you are allergic to quinapril; other ACE inhibitors such as benazepril (Lotensin, in Lotrel), captopril (Capoten), ...

  11. Inhibitory selectivity of canecystatin: a recombinant cysteine peptidase inhibitor from sugarcane

    The cDNA of a cystein peptidase inhibitor was isolated from sugarcane and expressed in Escherichia coli. The protein, named canecystatin, has previously been shown to exert antifungal activity on the filamentous fungus Trichoderma reesei. Herein, the inhibitory specificity of canecystatin was further characterized. It inhibits the cysteine peptidases from plant source papain (Ki=3.3 nM) and baupain (Ki=2.1x10-8 M), but no inhibitory effect was observed on ficin or bromelain. Canecystatin also inhibits lysosomal cysteine peptidases such as human cathepsin B (Ki=125 nM), cathepsin K (Ki=0.76 nM), cathepsin L (Ki=0.6 nM), and cathepsin V (Ki=1.0 nM), but not the aspartyl peptidase cathepsin D. The activity of serine peptidases such as trypsin, chymotrypsin, pancreatic, and neutrophil elastases, and human plasma kallikrein is not affected by the inhibitor, nor is the activity of the metallopeptidases angiotensin converting enzyme and neutral endopeptidase. This is the first report of inhibitory activity of a sugarcane cystatin on cysteine peptidases

  12. Preparation and antihypertensive activity of peptides from Porphyra yezoensis

    This research was to develop an antihypertensive peptide, an efficient angiotensin converting enzyme (ACE) inhibitor (ACEI), from Porphyra yezoensis. Seven commercial enzymes were screened and then enzymatic hydrolysis conditions were optimised. The results showed that alcalase was the most effectiv...

  13. Stereochemical course, isotope effects, and enzyme inhibitor studies of glaucine metabolism in fungi

    The microbial transformation of the aporphine alkaloid glaucine by the fungi Fusarium solani (ATCC 12823) and Aspergillus flavipes (ATCC 1030) proceeds with complete substrate stereoselectivity. The fungus F. solani metabolizes only S-(+)-glaucine (1) to dehydroglaucine (3), and A. flavipes metabolizes only R-(-)-glaucine (2) to dehydroglaucine. This facile microbiological reaction is useful in the destructive resolution of racemic mixtures of glaucine, and may provide a model for producing pure enantiomers (either R or S) of other aporphines from racemic mixtures. In order to extend the reaction to other aporphines and related alkaloids, the overall stereochemical course and enzyme(s) involved in the reaction, and the substrate requirements of the enzyme were investigated. The overall stereochemical course of the transformation was examined using C-7 methyl-blocked analogs of glaucine, cis- and trans-7-methylglaucine, as substrates for the fungi. Isolation and examination of residual substrates from semi-preparative scale incubations by MS, PMR, PMR with a chiral shift reagent, OR and ORD indicated that the transformation was enantioselective in the case of A. flavipes. However, only a 10% enrichment of 6aR,7R-cis-7-methylglaucine was observed in F. solani cultures. The oxidation of glaucine can be envisioned as proceeding through one of several mechanisms, each involving a different enzyme system. Deuterium isotope, induction and enzyme inhibitor experiments helped to distinguish between the three mechanisms

  14. Inhibitors of the Hydrolytic Enzyme Dimethylarginine Dimethylaminohydrolase (DDAH: Discovery, Synthesis and Development

    Rhys B. Murphy

    2016-05-01

    Full Text Available Dimethylarginine dimethylaminohydrolase (DDAH is a highly conserved hydrolytic enzyme found in numerous species, including bacteria, rodents, and humans. In humans, the DDAH-1 isoform is known to metabolize endogenous asymmetric dimethylarginine (ADMA and monomethyl arginine (l-NMMA, with ADMA proposed to be a putative marker of cardiovascular disease. Current literature reports identify the DDAH family of enzymes as a potential therapeutic target in the regulation of nitric oxide (NO production, mediated via its biochemical interaction with the nitric oxide synthase (NOS family of enzymes. Increased DDAH expression and NO production have been linked to multiple pathological conditions, specifically, cancer, neurodegenerative disorders, and septic shock. As such, the discovery, chemical synthesis, and development of DDAH inhibitors as potential drug candidates represent a growing field of interest. This review article summarizes the current knowledge on DDAH inhibition and the derived pharmacokinetic parameters of the main DDAH inhibitors reported in the literature. Furthermore, current methods of development and chemical synthetic pathways are discussed.

  15. Identifying New Drug Targets for Potent Phospholipase D Inhibitors: Combining Sequence Alignment, Molecular Docking, and Enzyme Activity/Binding Assays.

    Djakpa, Helene; Kulkarni, Aditya; Barrows-Murphy, Scheneque; Miller, Greg; Zhou, Weihong; Cho, Hyejin; Török, Béla; Stieglitz, Kimberly

    2016-05-01

    Phospholipase D enzymes cleave phospholipid substrates generating choline and phosphatidic acid. Phospholipase D from Streptomyces chromofuscus is a non-HKD (histidine, lysine, and aspartic acid) phospholipase D as the enzyme is more similar to members of the diverse family of metallo-phosphodiesterase/phosphatase enzymes than phospholipase D enzymes with active site HKD repeats. A highly efficient library of phospholipase D inhibitors based on 1,3-disubstituted-4-amino-pyrazolopyrimidine core structure was utilized to evaluate the inhibition of purified S. chromofuscus phospholipase D. The molecules exhibited inhibition of phospholipase D activity (IC50 ) in the nanomolar range with monomeric substrate diC4 PC and micromolar range with phospholipid micelles and vesicles. Binding studies with vesicle substrate and phospholipase D strongly indicate that these inhibitors directly block enzyme vesicle binding. Following these compelling results as a starting point, sequence searches and alignments with S. chromofuscus phospholipase D have identified potential new drug targets. Using AutoDock, inhibitors were docked into the enzymes selected from sequence searches and alignments (when 3D co-ordinates were available) and results analyzed to develop next-generation inhibitors for new targets. In vitro enzyme activity assays with several human phosphatases demonstrated that the predictive protocol was accurate. The strategy of combining sequence comparison, docking, and high-throughput screening assays has helped to identify new drug targets and provided some insight into how to make potential inhibitors more specific to desired targets. PMID:26691755

  16. Activity Based Profiling of Deubiquitylating Enzymes and Inhibitors in Animal Tissues.

    McLellan, Lauren; Forder, Cassie; Cranston, Aaron; Harrigan, Jeanine; Jacq, Xavier

    2016-01-01

    The attachment of ubiquitin or ubiquitin-like modifiers to proteins is an important signal for the regulation of a variety of biological processes including the targeting of substrates for degradation, receptor internalization, regulation of gene expression, and DNA repair. Posttranslational modification of proteins by ubiquitin controls many cellular processes, and aberrant ubiquitylation can contribute to cancer, immunopathologies, and neurodegeneration. Thus, deubiquitylating enzymes (DUBs) that remove ubiquitin from proteins have become attractive therapeutic targets. Monitoring the activity of DUBs in cells or in tissues is critical for understanding the biological function of DUBs in particular pathways and is essential for determining the physiological specificity and potency of small-molecule DUB inhibitors. Here, we describe a method for the homogenization of animal tissues and incubation of tissue lysates with ubiquitin-based activity probes to monitor DUB activity in mouse tissues and target engagement following treatment of animals with small-molecule DUB inhibitors. PMID:27613053

  17. Δ9-tetrahydrocannabinol and endocannabinoid degradative enzyme inhibitors attenuate intracranial self-stimulation in mice.

    Wiebelhaus, Jason M; Grim, Travis W; Owens, Robert A; Lazenka, Matthew F; Sim-Selley, Laura J; Abdullah, Rehab A; Niphakis, Micah J; Vann, Robert E; Cravatt, Benjamin F; Wiley, Jenny L; Negus, S Stevens; Lichtman, Aron H

    2015-02-01

    A growing body of evidence implicates endogenous cannabinoids as modulators of the mesolimbic dopamine system and motivated behavior. Paradoxically, the reinforcing effects of Δ(9)-tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis, have been difficult to detect in preclinical rodent models. In this study, we investigated the impact of THC and inhibitors of the endocannabinoid hydrolytic enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) on operant responding for electrical stimulation of the medial forebrain bundle [intracranial self-stimulation (ICSS)], which is known to activate the mesolimbic dopamine system. These drugs were also tested in assays of operant responding for food reinforcement and spontaneous locomotor activity. THC and the MAGL inhibitor JZL184 (4-[bis(1,3-benzodioxol-5-yl)hydroxymethyl]-1-piperidinecarboxylic acid 4-nitrophenyl ester) attenuated operant responding for ICSS and food, and also reduced spontaneous locomotor activity. In contrast, the FAAH inhibitor PF-3845 (N-3-pyridinyl-4-[[3-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]methyl]-1-piperidinecarboxamide) was largely without effect in these assays. Consistent with previous studies showing that combined inhibition of FAAH and MAGL produces a substantially greater cannabimimetic profile than single enzyme inhibition, the dual FAAH-MAGL inhibitor SA-57 (4-[2-(4-chlorophenyl)ethyl]-1-piperidinecarboxylic acid 2-(methylamino)-2-oxoethyl ester) produced a similar magnitude of ICSS depression as that produced by THC. ICSS attenuation by JZL184 was associated with increased brain levels of 2-arachidonoylglycerol (2-AG), whereas peak effects of SA-57 were associated with increased levels of both N-arachidonoylethanolamine (anandamide) and 2-AG. The cannabinoid receptor type 1 receptor antagonist rimonabant, but not the cannabinoid receptor type 2 receptor antagonist SR144528, blocked the attenuating effects of THC, JZL184, and SA-57 on

  18. Phage display-derived inhibitor of the essential cell wall biosynthesis enzyme MurF

    Blewett Ann

    2008-12-01

    Full Text Available Abstract Background To develop antibacterial agents having novel modes of action against bacterial cell wall biosynthesis, we targeted the essential MurF enzyme of the antibiotic resistant pathogen Pseudomonas aeruginosa. MurF catalyzes the formation of a peptide bond between D-Alanyl-D-Alanine (D-Ala-D-Ala and the cell wall precursor uridine 5'-diphosphoryl N-acetylmuramoyl-L-alanyl-D-glutamyl-meso-diaminopimelic acid (UDP-MurNAc-Ala-Glu-meso-A2pm with the concomitant hydrolysis of ATP to ADP and inorganic phosphate, yielding UDP-N-acetylmuramyl-pentapeptide. As MurF acts on a dipeptide, we exploited a phage display approach to identify peptide ligands having high binding affinities for the enzyme. Results Screening of a phage display 12-mer library using purified P. aeruginosa MurF yielded to the identification of the MurFp1 peptide. The MurF substrate UDP-MurNAc-Ala-Glumeso-A2pm was synthesized and used to develop a sensitive spectrophotometric assay to quantify MurF kinetics and inhibition. MurFp1 acted as a weak, time-dependent inhibitor of MurF activity but was a potent inhibitor when MurF was pre-incubated with UDP-MurNAc-Ala-Glu-meso-A2pm or ATP. In contrast, adding the substrate D-Ala-D-Ala during the pre-incubation nullified the inhibition. The IC50 value of MurFp1 was evaluated at 250 μM, and the Ki was established at 420 μM with respect to the mixed type of inhibition against D-Ala-D-Ala. Conclusion MurFp1 exerts its inhibitory action by interfering with the utilization of D-Ala-D-Ala by the MurF amide ligase enzyme. We propose that MurFp1 exploits UDP-MurNAc-Ala-Glu-meso-A2pm-induced structural changes for better interaction with the enzyme. We present the first peptide inhibitor of MurF, an enzyme that should be exploited as a target for antimicrobial drug development.

  19. Secoisolariciresinol Diglucoside (SDG) Isolated from Flaxseed, an Alternative to ACE Inhibitors in the Treatment of Hypertension

    Prasad, Kailash

    2013-01-01

    Secoisolariciresionol diglucoside (SDG) is a plant lignan isolated from flaxseed and is phytoestrogen. SDG is a potent and long-acting hypotensive agent. Plant phytoestrogens have inhibitory effects on angiotensin-converting enzyme (ACE). The hypotensive effects of SDG, a phytoestrogen, may be mediated through inhibition of ACE. The objective of this study was to investigate if SDG-induced hypotension is mediated through inhibition of ACE. The Sprague Dawley male rats were anesthetized and tr...

  20. Bauhinia proteinase inhibitor-based synthetic fluorogenic substrates for enzymes isolated from insect midgut and caterpillar bristles.

    Andrade, Sonia A; Santomauro-Vaz, Eugênio M; Lopes, Adriana R; Chudzinski-Tavassi, Ana M; Juliano, Maria A; Terra, Walter R; Sampaio, Misako U; Sampaio, Claudio A M; Oliva, Maria Luiza V

    2003-03-01

    Bauhinia ungulata factor Xa inhibitor (BuXI) inactivates factor Xa and LOPAP, a prothrombin activator proteinase isolated from the venom of Lonomia obliqua caterpillar bristles. The reactive site of the enzyme-inhibitor interaction was explored to design specific substrates for both enzymes. Methionine is crucial for LOPAP and factor Xa substrate interaction, since the change of both Met residues in the substrates abolished the hydrolysis. Synthetic substrates containing the sequence around the reactive site of BbKI, a plasma kallikrein inhibitor, were shown to be specific for trypsin hydrolysis. Therefore, these substrates may be an alternative in studies aiming at a characterization of trypsin-like enzyme activities, especially non-mammalian enzymes. PMID:12715900

  1. Treatment-emergent mutations in NAEβ confer resistance to the NEDD8-activating enzyme inhibitor MLN4924.

    Milhollen, Michael A; Thomas, Michael P; Narayanan, Usha; Traore, Tary; Riceberg, Jessica; Amidon, Benjamin S; Bence, Neil F; Bolen, Joseph B; Brownell, James; Dick, Lawrence R; Loke, Huay-Keng; McDonald, Alice A; Ma, Jingya; Manfredi, Mark G; Sells, Todd B; Sintchak, Mike D; Yang, Xiaofeng; Xu, Qing; Koenig, Erik M; Gavin, James M; Smith, Peter G

    2012-03-20

    MLN4924 is an investigational small-molecule inhibitor of NEDD8-activating enzyme (NAE) in clinical trials for the treatment of cancer. MLN4924 is a mechanism-based inhibitor, with enzyme inhibition occurring through the formation of a tight-binding NEDD8-MLN4924 adduct. In cell and xenograft models of cancer, we identified treatment-emergent heterozygous mutations in the adenosine triphosphate binding pocket and NEDD8-binding cleft of NAEβ as the primary mechanism of resistance to MLN4924. Biochemical analyses of NAEβ mutants revealed slower rates of adduct formation and reduced adduct affinity for the mutant enzymes. A compound with tighter binding properties was able to potently inhibit mutant enzymes in cells. These data provide rationales for patient selection and the development of next-generation NAE inhibitors designed to overcome treatment-emergent NAEβ mutations. PMID:22439935

  2. Regulatory proteins (inhibitors or activators) affect estimates of Msub(r) of enzymes and receptors by radiation inactivation

    The radiation-inactivation method allows the determination of the Msub(r) of enzymes and receptors by monitoring the decay of biological activity as a function of absorbed dose. The presence of regulatory or effector proteins (inhibitors or activators) associated with an enzyme or receptor, or released in the preparation after tissue homogenization, may affect the decay of biological activity. How the activity is affected, however, will depend on the type of inhibition (competitive or non-competitive), the inhibitor or activator concentration, the dissociation constant of the enzyme-effector system, and the effector Msub(r) relative to that of the enzyme. Since little is known on how effector proteins influence radiation inactivation of enzymes and receptors, we have considered a theoretical model in an effort to provide a framework for the interpretation of experimentally obtained data. Our model predicts that competitive and non-competitive inhibitors of enzymes could be distinguished by analysing irradiated samples with various substrate concentrations. Inhibitors will decrease whereas activators will increase the apparent target size of enzymes or receptors. (author)

  3. Anti-diabetic activity of insulin-degrading enzyme inhibitors mediated by multiple hormones.

    Maianti, Juan Pablo; McFedries, Amanda; Foda, Zachariah H; Kleiner, Ralph E; Du, Xiu Quan; Leissring, Malcolm A; Tang, Wei-Jen; Charron, Maureen J; Seeliger, Markus A; Saghatelian, Alan; Liu, David R

    2014-07-01

    Despite decades of speculation that inhibiting endogenous insulin degradation might treat type-2 diabetes, and the identification of IDE (insulin-degrading enzyme) as a diabetes susceptibility gene, the relationship between the activity of the zinc metalloprotein IDE and glucose homeostasis remains unclear. Although Ide(-/-) mice have elevated insulin levels, they exhibit impaired, rather than improved, glucose tolerance that may arise from compensatory insulin signalling dysfunction. IDE inhibitors that are active in vivo are therefore needed to elucidate IDE's physiological roles and to determine its potential to serve as a target for the treatment of diabetes. Here we report the discovery of a physiologically active IDE inhibitor identified from a DNA-templated macrocycle library. An X-ray structure of the macrocycle bound to IDE reveals that it engages a binding pocket away from the catalytic site, which explains its remarkable selectivity. Treatment of lean and obese mice with this inhibitor shows that IDE regulates the abundance and signalling of glucagon and amylin, in addition to that of insulin. Under physiological conditions that augment insulin and amylin levels, such as oral glucose administration, acute IDE inhibition leads to substantially improved glucose tolerance and slower gastric emptying. These findings demonstrate the feasibility of modulating IDE activity as a new therapeutic strategy to treat type-2 diabetes and expand our understanding of the roles of IDE in glucose and hormone regulation. PMID:24847884

  4. Yucasin is a potent inhibitor of YUCCA, a key enzyme in auxin biosynthesis.

    Nishimura, Takeshi; Hayashi, Ken-Ichiro; Suzuki, Hiromi; Gyohda, Atsuko; Takaoka, Chihiro; Sakaguchi, Yusuke; Matsumoto, Sachiko; Kasahara, Hiroyuki; Sakai, Tatsuya; Kato, Jun-Ichi; Kamiya, Yuji; Koshiba, Tomokazu

    2014-02-01

    Indole-3-acetic acid (IAA), an auxin plant hormone, is biosynthesized from tryptophan. The indole-3-pyruvic acid (IPyA) pathway, involving the tryptophan aminotransferase TAA1 and YUCCA (YUC) enzymes, was recently found to be a major IAA biosynthetic pathway in Arabidopsis. TAA1 catalyzes the conversion of tryptophan to IPyA, and YUC produces IAA from IPyA. Using a chemical biology approach with maize coleoptiles, we identified 5-(4-chlorophenyl)-4H-1,2,4-triazole-3-thiol (yucasin) as a potent inhibitor of IAA biosynthesis in YUC-expressing coleoptile tips. Enzymatic analysis of recombinant AtYUC1-His suggested that yucasin strongly inhibited YUC1-His activity against the substrate IPyA in a competitive manner. Phenotypic analysis of Arabidopsis YUC1 over-expression lines (35S::YUC1) demonstrated that yucasin acts in IAA biosynthesis catalyzed by YUC. In addition, 35S::YUC1 seedlings showed resistance to yucasin in terms of root growth. A loss-of-function mutant of TAA1, sav3-2, was hypersensitive to yucasin in terms of root growth and hypocotyl elongation of etiolated seedlings. Yucasin combined with the TAA1 inhibitor l-kynurenine acted additively in Arabidopsis seedlings, producing a phenotype similar to yucasin-treated sav3-2 seedlings, indicating the importance of IAA biosynthesis via the IPyA pathway in root growth and leaf vascular development. The present study showed that yucasin is a potent inhibitor of YUC enzymes that offers an effective tool for analyzing the contribution of IAA biosynthesis via the IPyA pathway to plant development and physiological processes. PMID:24299123

  5. Characterization of Cellulase Enzyme Inhibitors Formed During the Chemical Pretreatments of Rice Straw

    Rajan, Kalavathy

    Production of fuels and chemicals from a renewable and inexpensive resource such as lignocellulosic biomass is a lucrative and sustainable option for the advanced biofuel and bio-based chemical platform. Agricultural residues constitute the bulk of potential feedstock available for cellulosic fuel production. On a global scale, rice straw is the largest source of agricultural residues and is therefore an ideal crop model for biomass deconstruction studies. Lignocellulosic biofuel production involves the processes of biomass conditioning, enzymatic saccharification, microbial fermentation and ethanol distillation, and one of the major factors affecting its techno-economic feasibility is the biomass recalcitrance to enzymatic saccharification. Preconditioning of lignocellulosic biomass, using chemical, physico-chemical, mechanical and biological pretreatments, is often practiced such that biomass becomes available to downstream processing. Pretreatments, such as dilute acid and hot water, are effective means of biomass conversion. However, despite their processing importance, preconditioning biomass also results in the production of carbohydrate and lignin degradation products that are inhibitory to downstream saccharification enzymes. The saccharification enzyme cocktail is made up of endo-cellulase, exo-cellulase and beta-glucosidase enzymes, whose role is to cleave cellulose polymers into glucose monomers. Specifically, endo-cellulase and exo-cellulase enzymes cleave cellulose chains in the middle and at the end, resulting in cellobiose molecules, which are hydrolyzed into glucose by beta-glucosidase. Unfortunately, degradation compounds generated during pretreatment inhibit the saccharification enzyme cocktail. Various research groups have identified specific classes of inhibitors formed during biomass pretreatment and have studied their inhibitory effect on the saccharification cocktail. These various research groups prepared surrogate solutions in an attempt to

  6. Enzyme-Coupled Nanoparticles-Assisted Laser Desorption Ionization Mass Spectrometry for Searching for Low-Mass Inhibitors of Enzymes in Complex Mixtures

    Salwiński, Aleksander; Da Silva, David; Delépée, Raphaël; Maunit, Benoît

    2014-04-01

    In this report, enzyme-coupled magnetic nanoparticles (EMPs) were shown to be an effective affinity-based tool for finding specific interactions between enzymatic targets and the low-mass molecules in complex mixtures using classic MALDI-TOF apparatus. EMPs used in this work act as nonorganic matrix enabling ionization of small molecules without any interference in the low-mass range (enzyme-coupled nanoparticles-assisted laser desorption ionization MS, ENALDI MS) and simultaneously carry the superficial specific binding sites to capture inhibitors present in a studied mixture. We evaluated ENALDI approach in two complementary variations: `ion fading' (IF-ENALDI), based on superficial adsorption of inhibitors and `ion hunting' (IH-ENALDI), based on selective pre-concentration of inhibitors. IF-ENALDI was applied for two sets of enzyme-inhibitor pairs: tyrosinase-glabridin and trypsin-leupeptin and for the real plant sample: Sparrmannia discolor leaf and stem methanol extract. The efficacy of IH-ENALDI was shown for the pair of trypsin-leupeptin. Both ENALDI approaches pose an alternative for bioassay-guided fractionation, the common method for finding inhibitors in the complex mixtures.

  7. A cautionary tale of structure-guided inhibitor development against an essential enzyme in the aspartate-biosynthetic pathway.

    Pavlovsky, Alexander G; Thangavelu, Bharani; Bhansali, Pravin; Viola, Ronald E

    2014-12-01

    The aspartate pathway is essential for the production of the amino acids required for protein synthesis and of the metabolites needed in bacterial development. This pathway also leads to the production of several classes of quorum-sensing molecules that can trigger virulence in certain microorganisms. The second enzyme in this pathway, aspartate β-semialdehyde dehydrogenase (ASADH), is absolutely required for bacterial survival and has been targeted for the design of selective inhibitors. Fragment-library screening has identified a new set of inhibitors that, while they do not resemble the substrates for this reaction, have been shown to bind at the active site of ASADH. Structure-guided development of these lead compounds has produced moderate inhibitors of the target enzyme, with some selectivity observed between the Gram-negative and Gram-positive orthologs of ASADH. However, many of these inhibitor analogs and derivatives have not yet achieved the expected enhanced affinity. Structural characterization of these enzyme-inhibitor complexes has provided detailed explanations for the barriers that interfere with optimal binding. Despite binding in the same active-site region, significant changes are observed in the orientation of these bound inhibitors that are caused by relatively modest structural alterations. Taken together, these studies present a cautionary tale for issues that can arise in the systematic approach to the modification of lead compounds that are being used to develop potent inhibitors. PMID:25478842

  8. Pretreatment with ACE inhibitors improves acute outcome of electrical cardioversion in patients with persistent atrial fibrillation

    Van Veldhuisen Dirk J

    2005-01-01

    Full Text Available Abstract Background Persistent atrial fibrillation (AF is difficult to treat. In the absence of class I or III antiarrhythmic drugs sinus rhythm is maintained in only 30% of patients during the first year after electrical cardioversion (ECV. One of the remodeling processes induced by AF is fibrosis, which relates to inducibility and maintenance of AF. The renin-angiotensin system may play a important role in this. The aim of this study was to investigate the role of angiotensin-converting enzyme (ACE inhibitor use on efficacy of ECV, and occurrence of subacute recurrences. Methods One hundred-seven consecutive patients with persistent AF underwent ECV. In twenty-eight (26% patients ACE inhibitors had been started before initiation of the present episode of AF ('pre-treated' patients. Results ECV was successful in 96% of patients who were on ACE inhibitors before start of the present episode of AF compared to 80% of the patients not pre-treated (p = 0.04. After 1 month of follow-up 49% of the pre-treated patients and 50% of those not pre-treated with ACE inhibition were still in sinus rhythm (p=ns. Multivariate analysis showed that pre-treatment with ACE inhibitors and a smaller left atrial size were independent predictors of successful ECV (OR = 5.8, C.I. 1.3–26.1, and OR = 5.6, C.I. 1.2–25.3, respectively. Conclusions Pre-treatment with ACE inhibitors may improve acute success of ECV but does not prevend AF recurrences.

  9. Chronic ACE inhibitor treatment increases angiotensin type 1 receptor binding in vivo in the dog kidney

    Zober, Tamas G. [Johns Hopkins University, Departments of Radiology and Surgery, Baltimore, MD (United States); Semmelweis University, Department of Pathophysiology, Budapest (Hungary); Fabucci, Maria E.; Zheng, Wei; Sandberg, Kathryn [Georgetown University, Department of Medicine, Washington, DC (United States); Brown, Phillip R.; Seckin, Esen; Mathews, William B. [Johns Hopkins University, Departments of Radiology and Surgery, Baltimore, MD (United States); Szabo, Zsolt [Johns Hopkins University, Departments of Radiology and Surgery, Baltimore, MD (United States); Johns Hopkins Outpatient Center, Division of Nuclear Medicine, Baltimore, MD (United States)

    2008-06-15

    PET imaging has been recently introduced for investigating the type 1 angiotensin II receptor (AT{sub 1}R) in vivo. The goal of the present study was to investigate the effects of acute and chronic exposure to angiotensin converting enzyme inhibitors (ACEI) on the AT{sub 1}R in the dog kidney. Animals were imaged at baseline, after acute intravenous ACEI treatment and after a chronic 2-week exposure to an oral ACEI. Control animals were imaged at identical time points in the absence of ACEI treatment. In vivo AT{sub 1}R binding expressed by K{sub i} was increased in the renal cortex by chronic ACEI treatment (p < 0.05). In vitro measurements of AT{sub 1}R density (B{sub max}) also revealed significant increases in AT{sub 1}R in isolated glomeruli (p < 0.05). Plasma renin activity was increased, but angiotensin II (Ang II) and the Ang II/Ang I ratio showed a weak correlation with chronic ACEI treatment, consistent with an Ang II escape phenomenon. This study reveals, for the first time, that chronic ACEI treatment increases AT{sub 1}R binding in vivo in the dog renal cortex. (orig.)

  10. Discriminative Stimulus Properties of the Endocannabinoid Catabolic Enzyme Inhibitor SA-57 in Mice.

    Owens, Robert A; Ignatowska-Jankowska, Bogna; Mustafa, Mohammed; Beardsley, Patrick M; Wiley, Jenny L; Jali, Abdulmajeed; Selley, Dana E; Niphakis, Micah J; Cravatt, Benjamin F; Lichtman, Aron H

    2016-08-01

    Whereas the inhibition of fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL), the respective major hydrolytic enzymes of N-arachidonoyl ethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), elicits no or partial substitution for Δ(9)-tetrahydrocannabinol (THC) in drug-discrimination procedures, combined inhibition of both enzymes fully substitutes for THC, as well as produces a constellation of cannabimimetic effects. The present study tested whether C57BL/6J mice would learn to discriminate the dual FAAH-MAGL inhibitor SA-57 (4-[2-(4-chlorophenyl)ethyl]-1-piperidinecarboxylic acid 2-(methylamino)-2-oxoethyl ester) from vehicle in the drug-discrimination paradigm. In initial experiments, 10 mg/kg SA-57 fully substituted for CP55,940 ((-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol), a high-efficacy CB1 receptor agonist in C57BL/6J mice and for AEA in FAAH (-/-) mice. Most (i.e., 23 of 24) subjects achieved criteria for discriminating SA-57 (10 mg/kg) from vehicle within 40 sessions, with full generalization occurring 1 to 2 hours postinjection. CP55,940, the dual FAAH-MAGL inhibitor JZL195 (4-​nitrophenyl 4-​(3-​phenoxybenzyl)piperazine-​1-​carboxylate), and the MAGL inhibitors MJN110 (2,5-dioxopyrrolidin-1-yl 4-(bis(4-chlorophenyl)methyl)piperazine-1-carboxylate) and JZL184 (4-[Bis(1,3-benzodioxol-5-yl)hydroxymethyl]-1-piperidinecarboxylic acid 4-nitrophenyl ester) fully substituted for SA-57. Although the FAAH inhibitors PF-3845 ((N-3-pyridinyl-4-[[3-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]methyl]-1-piperidinecarboxamide) and URB597 (cyclohexylcarbamic acid 3'-(aminocarbonyl)-[1,1'-biphenyl]-3-yl ester) did not substitute for SA-57, PF-3845 produced a 2-fold leftward shift in the MJN110 substitution dose-response curve. In addition, the CB1 receptor antagonist rimonabant blocked the generalization of SA-57, as well as substitution of CP55,940, JZL195, MJN110, and JZL184. These findings

  11. A systematic review on randomized control trials on rennin angiotensin aldosterone system inhibitors role in managing hypertension among hemodialysis patients.

    Aftab, Raja Ahsan; Khan, Amer Hayat; Adnan, Azreen Syazril; Jannah, Nurul

    2016-01-01

    Randomized control trials (RCTs) are considered as most rigors way of determining the cause-effect relationship of a treatment and outcome. Activation of rennin angiotensin aldosterone system (RAAS) is an important contributor to hypertension in hemodialysis patients. The prevalence of hypertension in hemodialysis patients varies from 60% to 80% and hypertension management alone with conventional hemodialysis is insufficient. Hence, the current review was aimed to investigate the effect of RAAS inhibitors in managing hypertension among hemodialysis patients in a randomized control trial. Using PUBMED and EMBASE databases, randomized control trial with primary or secondary outcomes related to the effect of RAAS inhibitors on blood pressure among hemodialysis patients were included for analysis. The current review also assessed the quality of reporting of RCT. A total of eight RCT met inclusion criteria for current review. According to modified jaded scale, one (12.5%) study scored four points for quality reporting, whereas two (25%) studies scored one point that was the least score. The mean score for all included studies was 2.25. Six (75%) of the eight RCT included, involved ARB in hypertension management among hemodialysis patients, whereas two (25%) studies involved angiotensin-converting enzyme (ACE) inhibitors. Of the siz RCT involving ARB, two (33.3%) RCT also included ACE inhibitors comparison group. Altogether six (75%) studies report a reduction in blood pressure with the use of RAAS inhibitors compared to control group; however, of the six studies, two (33.3%) reported that the reduction in blood pressure was not significant. Whereas, two (25%) studies reported no reduction in blood pressure compared to the control group. The findings from current review do not indicate a clear pattern for a role of RAAS inhibitors for hypertension control among hemodialysis patients. PMID:26853680

  12. Diabetic encephalopathy: a cerebrovascular disorder?

    Manschot, S.M.

    2006-01-01

    Animal study: The aim was to investigate the role of vascular disturbances in the development of experimental diabetic encephalopathy. We describe the effects of treatment with the Angiotensin Converting Enzyme(ACE)-inhibitor enalapril (treatment aimed at the vasculature)

  13. High Blood Pressure Medicines

    ... your blood to pass through more easily. Alpha-beta blockers not only reduce nerve impulses, but also make ... with less force. They combine the effects of beta blockers and alpha blockers. Angiotensin-converting enzyme inhibitors (also ...

  14. Potassium Test

    ... non-steroidal anti-inflammatory drugs (NSAIDs) , ACE inhibitors, beta blockers (such as propanolol and atenolol), angiotensin-converting enzyme ... be due to certain drugs such as NSAIDs, beta blockers, and lithium or due to the adrenal glands ...

  15. Cost effectiveness analysis of improved blood pressure control in hypertensive patients with type 2 diabetes: UKPDS 40

    1998-01-01

    Objectives: To estimate the economic efficiency of tight blood pressure control, with angiotensin converting enzyme inhibitors or β blockers, compared with less tight control in hypertensive patients with type 2 diabetes.

  16. Drug: D01667 [KEGG MEDICUS

    Full Text Available 489.0036 D01667.gif Antihypertensive; Enzyme inhibitor [angiotensin-converting] Therapeutic category: 2144 ...ic category of drugs in Japan [BR:br08301] 2 Agents affecting individual organs 21 Cardiovascular agents 214 Antihypertensive

  17. Drug: D00251 [KEGG MEDICUS

    Full Text Available 217.2853 D00251.gif Antihypertensive; Enzyme inhibitor [angiotensin-converting] Therapeutic category: 2144 ...category of drugs in Japan [BR:br08301] 2 Agents affecting individual organs 21 Cardiovascular agents 214 Antihypertensive

  18. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39

    1998-01-01

    Objective: To determine whether tight control of blood pressure with either a β blocker or an angiotensin converting enzyme inhibitor has a specific advantage or disadvantage in preventing the macrovascular and microvascular complications of type 2 diabetes.

  19. Effects of sulodexide in patients with type 2 diabetes and persistent albuminuria

    Heerspink, Hiddo Lambers; Greene, Tom; Lewis, Julia B.; Raz, Itamar; Rohde, Richard D.; Hunsicker, Lawrence G.; Schwartz, Sherwyn L.; Aronoff, Stephen; Katz, Murray A.; Eisner, Gilbert M.; Mersey, James H.; Wiegmann, Thomas B.

    2008-01-01

    Background. Urinary albumin excretion frequently persists in diabetic patients who are treated with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Sulodexide, a glycosaminoglycan mixture of 80% heparan sulfate and 20% dermatan sulfate, has been hypothesized t

  20. Captopril

    ... angiotensin-converting enzyme (ACE) inhibitors. It decreases certain chemicals that tighten the blood vessels, so blood flows ... metallic taste, or decreased ability to taste cough fast heartbeat ... the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting ...