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Sample records for converting enzyme inhibitor

  1. Angiotensin-converting enzyme inhibitors in congestive heart failure.

    Science.gov (United States)

    Deedwania, P C

    1990-09-01

    Angiotensin-converting enzyme inhibitors have had a significant impact on the treatment of congestive heart failure (CHF). Hemodynamic and clinical improvements in patients with severe CHF fostered the use of angiotensin-converting enzyme inhibitors in mild to moderate CHF. Angiotensin-converting enzyme inhibitors produce acute and sustained improvements in ventricular hemodynamics and quality of life. Captopril plus diuretic therapy is an effective alternative to digoxin in patients with mild to moderate CHF. Enalapril maleate and lisinopril have been shown to be effective in moderate to severe CHF when combined with digoxin and diuretics. Captopril and enalapril also improve survival in selected patients; captopril attenuates left ventricular dilatation after myocardial infarction. Although all angiotensin-converting enzyme inhibitors are similar in mechanism of action, pharmacokinetic differences impact their clinical use. Prolonged symptomatic hypotension compromising systemic perfusion and organ function has been reported with longer-acting agents; hypotension is usually short-lived and rarely compromises organ function with shorter-acting agents.

  2. Inhibitor and substrate binding by angiotensin-converting enzyme

    DEFF Research Database (Denmark)

    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...... mechanical (QM/MM) approach. The structural parameters obtained from the 550 ps molecular dynamics simulations are in excellent agreement with the X-ray structures, validating the QM/MM approach. Based on these structures, a model for the Michaelis complex was proposed and simulated using the same...

  3. Inhaled sodium cromoglycate in angiotensin-converting enzyme inhibitor cough.

    Science.gov (United States)

    Hargreaves, M R; Benson, M K

    1995-01-07

    Cough is a frequent side-effect of angiotensin-converting enzyme (ACE) inhibitors. We examined the effects of inhaled sodium cromoglycate in 10 patients with ACE-inhibitor cough in a double-blind crossover study. After a 2-week run-in, patients were randomised to either 2 weeks' inhaled sodium cromoglycate or placebo followed by a further 2 weeks on the other treatment. Patients kept a cough diary during each study period. Cough severity was recorded on a scale from 0 to 12. At the end of each study period the cough threshold to inhaled capsaicin was measured. 9 patients reported a reduction in cough after sodium cromoglycate. Median (range) daily cough scores during run-in and placebo periods were 3.6 (1.9-6.4) and 4.1 (0.6-8.1), respectively (p > 0.05). Median daily cough score after sodium cromoglycate was 1.8 (0.4-3; p sodium cromoglycate; and cough-reflex sensitivity to inhaled capsaicin was significantly reduced. Inhaled sodium cromoglycate is an effective treatment for ACE-inhibitor cough. Its effect may be due to suppression of afferent vagal activity.

  4. Quantum Chemistry Calculation of Angiotensin Converting Enzyme Inhibitors

    Institute of Scientific and Technical Information of China (English)

    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.

  5. Angioedema Related to Angiotensin-Converting Enzyme Inhibitors

    Science.gov (United States)

    Javaud, Nicolas; Achamlal, Jallal; Reuter, Paul-George; Lapostolle, Frédéric; Lekouara, Akim; Youssef, Mustapha; Hamza, Lilia; Karami, Ahmed; Adnet, Frédéric; Fain, Olivier

    2015-01-01

    Abstract The number of cases of acquired angioedema related to angiotensin converting enzyme inhibitors induced (ACEI-AAE) is on the increase, with a potential concomitant increase in life-threatening attacks of laryngeal edema. Our objective was to determine the main characteristics of ACEI-AAE attacks and, in doing so, the factors associated with likelihood of hospital admission from the emergency department (ED) after a visit for an attack. A prospective, multicenter, observational study (April 2012–December 2014) was conducted in EDs of 4 French hospitals in collaboration with emergency services (SAMU 93) and a reference center for bradykinin-mediated angioedema. For each patient presenting with an attack, emergency physicians collected demographic and clinical presentation data, treatments, and clinical course. They recorded time intervals from symptom onset to ED arrival and to treatment decision, from ED arrival to specific treatment with plasma-derived C1-inhibitor (C1-INH) or icatibant, and from specific treatment to onset of symptom relief. Attacks requiring hospital admission were compared with those not requiring admission. Sixty-two eligible patients with ACEI-AAE (56% men, median age 63 years) were included. Symptom relief occurred significantly earlier in patients receiving specific treatment than in untreated patients (0.5 [0.5–1.0] versus 3.9 [2.5–7.0] hours; P < 0.0001). Even though icatibant was injected more promptly than plasma-derived C1-INH, there, however, was no significant difference in median time to onset of symptom relief between the 2 drugs (0.5 [0.5–1.3] versus 0.5 [0.4–1.0] hours for C1-INH and icatibant, respectively, P = 0.49). Of the 62 patients, 27 (44%) were admitted to hospital from the ED. In multivariate analysis, laryngeal involvement and progressive swelling at ED arrival were independently associated with admission (Odds ratio [95% confidence interval] = 6.2 [1.3–28.2] and 5.9 [1.3–26

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

    DEFF Research Database (Denmark)

    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....

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

    Science.gov (United States)

    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

  8. Angiotensin-Converting Enzyme Inhibitors and Active Tuberculosis

    Science.gov (United States)

    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. Adverse drug reactions of angiotensin converting enzyme inhibitors : towards precision medicine

    NARCIS (Netherlands)

    Mahmoud Pour, S.H.

    2016-01-01

    Worldwide, millions of patients with cardiovascular diseases are treated with angiotensin converting enzyme inhibitors (ACEIs) according to the international treatment guidelines. Although this class of medications is generally well tolerated, adverse drug reactions (ADRs) may prevent their use in s

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

    DEFF Research Database (Denmark)

    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 (con...

  11. [Arteriosclerosis obliterans. Treatment with angiotensin-converting enzyme inhibitors].

    Science.gov (United States)

    Orea, A; Valdés, R; Niebla, L; Rivas, R; Camacho, B

    1990-01-01

    We compare the effects of two of the main angiotensin convertase enzyme inhibitors, captopril and enalapril, aiming to evaluate their effects in the arterial circulation performance, micro-circulation, and changes in regional blood flow, assuming their property of lowering the angiotensin II blood levels, a very strong peripheral vasoconstrictor. We studied 22 patients: all of them with hypertension and/or skin ulcerations, dropping out those who had venous. They were evaluated periodically, clinically and with photoelectric plethysmography of lower extremities. To interpret the traces we designed an ideogram which gathered the plethysmographic behavior before and after the treatment. Nearly 80% showed considerable improvement in pain, functional capacity and plethysmographic traces patterns. healing of the ulcerations was achieved in all case. We propose some hypothesis to explain the good effect that we have observed.

  12. Outcomes with Angiotensin-converting Enzyme Inhibitors vs Other Antihypertensive Agents in Hypertensive Blacks.

    Science.gov (United States)

    Bangalore, Sripal; Ogedegbe, Gbenga; Gyamfi, Joyce; Guo, Yu; Roy, Jason; Goldfeld, Keith; Torgersen, Christopher; Capponi, Louis; Phillips, Christopher; Shah, Nirav R

    2015-11-01

    Angiotensin-converting enzyme inhibitors are used widely in the treatment of patients with hypertension. However, their efficacy in hypertensive blacks when compared with other antihypertensive agents is not well established. We performed a cohort study of patients using data from a clinical data warehouse of 434,646 patients from New York City's Health and Hospitals Corporation from January 2004 to December 2009. Patients were divided into the following comparison groups: angiotensin-converting enzyme inhibitors vs calcium channel blockers, angiotensin-converting enzyme inhibitors vs thiazide diuretics, and angiotensin-converting enzyme inhibitors vs β-blockers. The primary outcome was a composite of death, myocardial infarction, and stroke. Secondary outcomes included the individual components and heart failure. In the propensity score-matched angiotensin-converting enzyme inhibitors vs calcium channel blocker comparison cohort (4506 blacks in each group), angiotensin-converting enzyme inhibitors were associated with a higher risk of primary outcome (hazard ratio [HR], 1.45; 95% confidence interval [CI], 1.19-1.77; P = .0003), myocardial infarction (HR, 3.40; 95% CI, 1.25-9.22; P = .02), stroke (HR, 1.82; 95% CI, 1.29-2.57; P = .001), and heart failure (HR, 1.77; 95% CI, 1.30-2.42; P = .0003) when compared with calcium channel blockers. For the angiotensin-converting enzyme inhibitors vs thiazide diuretics comparison (5337 blacks in each group), angiotensin-converting enzyme inhibitors were associated with a higher risk of primary outcome (HR, 1.65; 95% CI, 1.33-2.05; P < .0001), death (HR, 1.35; 95% CI, 1.03-1.76; P = .03), myocardial infarction (HR, 4.00; 95% CI, 1.34-11.96; P = .01), stroke (HR, 1.97; 95% CI, 1.34-2.92; P = .001), and heart failure (HR, 3.00; 95% CI, 1.99-4.54; P < .0001). For the angiotensin-converting enzyme inhibitors vs β-blocker comparison, the outcomes between the groups were not significantly different. In a real-world cohort of

  13. The evolution of renin-angiotensin blockade: angiotensin-converting enzyme inhibitors as the starting point.

    Science.gov (United States)

    Sica, Domenic A

    2010-04-01

    The renin-angiotensin system has been a target in the treatment of hypertension for close to three decades. Several medication classes that block specific aspects of this system have emerged as useful therapies, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and, most recently, direct renin inhibitors. There has been a natural history to the development of each of these three drug classes, starting with their use as antihypertensive agents; thereafter, in each case they have been employed as end-organ protective agents. To date, there has been scant evidence to favor angiotensin receptor blockers or direct renin inhibitors over angiotensin-converting enzyme inhibitors in treating hypertension or in affording end-organ protection; thus, angiotensin-converting enzyme inhibitors remain the standard of care when renin-angiotensin system blockade is warranted.

  14. Role of angiotensin-converting enzyme inhibitor, lisinopril, on spermatozoal functions in rats.

    Science.gov (United States)

    Saha, L; Garg, S K; Bhargava, V K; Mazumdar, S

    2000-04-01

    Angiotensin-converting enzyme is present in the male reproductive system but its role in the physiology of reproduction is not known. To see the effect of angiotensin-converting enzyme on spermatozoal functions, lisinopril, an angiotensin-converting enzyme inhibitor, was administered orally using two different doses (10 and 20 mg/kg/day) to rats. Both short-term (2 weeks) and long-term (6 weeks) effects of the drug were observed. Lisinopril treatment resulted in a marked decrease in sperm density, sperm motility and zona pellucida penetration. Acrosome reaction by spermatozoa obtained from drug-treated animals was significantly lower when compared with spermatozoa from normal animals.

  15. High prevalence of persistent cough with angiotensin converting enzyme inhibitors in Chinese.

    OpenAIRE

    Woo, K. S.; Nicholls, M G

    1995-01-01

    1. Angiotensin converting enzyme (ACE) inhibitors are in common use for the treatment of hypertension and heart failure. Whereas they are, in general, well tolerated, a dry cough can develop which, on occasion, requires termination of therapy. The reported prevalence of cough with ACE inhibitor therapy has varied from 0.2 to 25%, depending upon methods of data collection, analysis and symptom reporting. 2. To evaluate the prevalence of cough in Chinese patients receiving ACE inhibitors, inter...

  16. Assessment of 105 Patients with Angiotensin Converting Enzyme-Inhibitor Induced Angioedema

    Science.gov (United States)

    von Buchwald, Christian; Prasad, Sumangali Chandra; Kamaleswaran, Shailajah; Ajgeiy, Kawa Khaled; Authried, Georg; Pallesen, Kristine Appel U.

    2017-01-01

    Objective. To asses a cohort of 105 consecutive patients with angiotensin converting enzyme-inhibitor induced angioedema with regard to demographics, risk factors, family history of angioedema, hospitalization, airway management, outcome, and use of diagnostic codes used for the condition. Study Design. Cohort study. Methods. This was a retrospective cohort study of 105 patients with angiotensin converting enzyme-inhibitor induced angioedema in the period 1995–2014. Results. The cohort consisted of 67 females and 38 males (F : M ratio 1.8), with a mean age of 63 [range 26–86] years. Female gender was associated with a significantly higher risk of angiotensin converting enzyme-inhibitor induced angioedema. 6.7% had a positive family history of angioedema. Diabetes seemed to be a protective factor with regard to angioedema. 95% experienced angioedema of the head and neck. 4.7% needed intubation or tracheostomy. 74 admissions took place during the study period with a total of 143 days spent in the hospital. The diagnosis codes most often used for this condition were “DT783 Quincke's oedema” and “DT78.4 Allergy unspecified”. Complement C1 inhibitor was normal in all tested patients. Conclusion. Female gender predisposes to angiotensin converting enzyme-inhibitor induced angioedema, whereas diabetes seems to be a protective factor. PMID:28286522

  17. Assessment of 105 Patients with Angiotensin Converting Enzyme-Inhibitor Induced Angioedema

    Directory of Open Access Journals (Sweden)

    Eva Rye Rasmussen

    2017-01-01

    Full Text Available Objective. To asses a cohort of 105 consecutive patients with angiotensin converting enzyme-inhibitor induced angioedema with regard to demographics, risk factors, family history of angioedema, hospitalization, airway management, outcome, and use of diagnostic codes used for the condition. Study Design. Cohort study. Methods. This was a retrospective cohort study of 105 patients with angiotensin converting enzyme-inhibitor induced angioedema in the period 1995–2014. Results. The cohort consisted of 67 females and 38 males (F : M ratio 1.8, with a mean age of 63 [range 26–86] years. Female gender was associated with a significantly higher risk of angiotensin converting enzyme-inhibitor induced angioedema. 6.7% had a positive family history of angioedema. Diabetes seemed to be a protective factor with regard to angioedema. 95% experienced angioedema of the head and neck. 4.7% needed intubation or tracheostomy. 74 admissions took place during the study period with a total of 143 days spent in the hospital. The diagnosis codes most often used for this condition were “DT783 Quincke’s oedema” and “DT78.4 Allergy unspecified”. Complement C1 inhibitor was normal in all tested patients. Conclusion. Female gender predisposes to angiotensin converting enzyme-inhibitor induced angioedema, whereas diabetes seems to be a protective factor.

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

    DEFF Research Database (Denmark)

    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-hexen...

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

    LENUS (Irish Health Repository)

    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.

  20. Angiotensin-converting enzyme inhibitor treatment and the development of urinary tract infection

    NARCIS (Netherlands)

    Pouwels, Koen; Visser, Sipke; Bos, Jens; Hak, Eelko

    2013-01-01

    Background: Angiotensin-converting enzyme inhibitors (ACEi) can reduce the urine output, especially when treatment is started. Since bacterial clearance from the urinary tract is dependent on the urine output, it was hypothesized that ACEi may also increase the risk of urinary tract infections (UTIs

  1. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in patients with abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Kristensen, Karl Emil; Torp-Pedersen, Christian; Gislason, Gunnar Hilmar;

    2015-01-01

    OBJECTIVE: The renin-angiotensin system is thought to play a pivotal role in the pathogenesis of abdominal aortic aneurysms (AAAs). However, effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs) on human AAAs remain unclear. We therefore ex...

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

    DEFF Research Database (Denmark)

    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...

  3. Angiotensin-converting enzyme inhibitor treatment and the development of urinary tract infection

    NARCIS (Netherlands)

    Pouwels, Koen; Visser, Sipke; Bos, Jens; Hak, Eelko

    2013-01-01

    Background: Angiotensin-converting enzyme inhibitors (ACEi) can reduce the urine output, especially when treatment is started. Since bacterial clearance from the urinary tract is dependent on the urine output, it was hypothesized that ACEi may also increase the risk of urinary tract infections

  4. Angiotensin-converting enzyme inhibitor use and protection against pneumonia in patients with diabetes

    NARCIS (Netherlands)

    van de Garde, Ewoudt M W; Souverein, Patrick C; Hak, Eelko; Deneer, Vera H M; van den Bosch, Jules M M; Leufkens, Hubert G M

    2007-01-01

    OBJECTIVES: Because of the high risk of pneumonia in patients with diabetes, we aimed to assess the effect of angiotensin-converting enzyme (ACE) inhibitor use on the occurrence of pneumonia in a general population of patients with diabetes. METHODS: The study population comprised all patients in th

  5. Are angiotensin converting enzyme inhibitors superior to beta blockers in retarding progressive renal function decline?

    NARCIS (Netherlands)

    vanEssen, GG; Apperloo, AJ; Rensma, PL; Stegeman, CA; Sluiter, WJ; deZeeuw, D; deJong, PE

    1997-01-01

    We questioned the superiority of angiotensin converting enzyme (ACE) inhibitors to beta blocking drugs with regard to renal function outcome in patients with mild to moderate renal insufficiency and normal to moderately elevated blood pressure (BP). We therefore studied 89 patients in a prospective

  6. Assessment of 105 Patients with Angiotensin Converting Enzyme-Inhibitor Induced Angioedema

    DEFF Research Database (Denmark)

    Rasmussen, Eva Rye; von Buchwald, Christian; Wadelius, Mia

    2017-01-01

    Objective. To asses a cohort of 105 consecutive patients with angiotensin converting enzyme-inhibitor induced angioedema with regard to demographics, risk factors, family history of angioedema, hospitalization, airway management, outcome, and use of diagnostic codes used for the condition. Study ...

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

    OpenAIRE

    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.

  8. Angiotensin converting enzyme inhibitor associated cough: a population-based case-control study.

    NARCIS (Netherlands)

    Visser, L.E.; Stricker, B.H.C.; Velden, J. van der; Paes, A.H.P.; Bakker, A.

    1995-01-01

    The objectives of this study were to determine the risk for coughing as an adverse reaction to angiotensin converting enzyme (ACE) inhibitors under everyday circumstances in a large population and to study whether this adverse effect is more common in women. A population-based case-control study was

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: Angiotensin converting enzyme-inhibitors (ACEIs) are the first-line treatment for patients with heart failure (HF) with reduced ejection fraction (EF). The benefit of ACEIs in HF is regarded as a class effect and different types of agents are used interchangeably. However, evidence...

  10. Visual hallucinations related to angiotensin-converting enzyme inhibitor use: case reports and review.

    Science.gov (United States)

    Doane, John; Stults, Barry

    2013-04-01

    Four patients experienced visual hallucinations that appear to have been precipitated by lisinopril. Other cases of visual hallucinations have been reported with other angiotensin-converting enzyme (ACE) inhibitors. Older patients, particularly those with a history of either dementia or mild cognitive impairment, may be at higher risk. Hallucinations resolved within 1 to 30 days after cessation of ACE inhibitors. Development of visual hallucinations after initiation of ACE inhibitors should prompt discontinuation of therapy. Visual hallucinations have been reported in one case involving an ARB. Visual hallucinations have not been associated with direct renin inhibitors. Consideration should be given to use of alternative, unrelated antihypertensive drug classes.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    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...... 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...

  12. Icatibant in the Treatment of Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema

    Directory of Open Access Journals (Sweden)

    Neil H. Crooks

    2014-01-01

    Full Text Available We describe the case of a 75-year-old woman who presented with massive tongue and lip swelling secondary to angiotensin-converting enzyme inhibitor-induced angioedema. An awake fibre-optic intubation was performed because of impending airway obstruction. As there was no improvement in symptoms after 72 hours, the selective bradykinin B2 receptor antagonist icatibant (Firazyr was administered and the patient’s trachea was successfully extubated 36 hours later. To our knowledge this is the first documented case of icatibant being used for the treatment of angiotensin-converting enzyme inhibitor-induced angioedema in the United Kingdom and represents a novel therapeutic option in its management.

  13. Design, synthesis and biological activity of novel non-peptidyl endothelin converting enzyme inhibitors, 1-phenyl-tetrazole-formazan analogues.

    Science.gov (United States)

    Yamazaki, Kazuto; Hasegawa, Hirohiko; Umekawa, Kayo; Ueki, Yasuyuki; Ohashi, Naohito; Kanaoka, Masaharu

    2002-05-06

    A novel non-peptidyl endothelin converting enzyme inhibitor was obtained through a pharmacophore analysis of known inhibitors and three-dimensional structure database search. Analogues of the new inhibitor were designed using the structure-activity relationship of known inhibitors and synthesized. In anesthetized rats, intraperitoneal administration of the analogues suppressed the pressor responses induced by big endothelin-1.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Medical treatments in aortic stenosis: Role of statins and angiotensin-converting enzyme inhibitors

    Directory of Open Access Journals (Sweden)

    Davičević Žaklina

    2010-01-01

    Full Text Available Calcific arotic stenosis and atherosclerosis. Aortic stenosis is the most frequent valvular heart disease in-western world and its incidence continues to rise. Aortic sclerosis is the first characteristic lesion of the cusps, which is today considered a process similar to atherosclerosis. The progression of the disease is an active process leading to forming of bone matrix and heavily calcified stiff cusps by inflammatory cells and osteopontin. Aortic stenosis is a chronic, progressive disease which can remain asymptomatic for a long time even in the presence of severe aortic stenosis. Medical treatment for aortic stenosis. The need for alternative to aortic valve surgery is highlighted by increasing longevity of the population and new therapeutic strategies to limit disease progression are needed to delay or potentially avoid, the need for valve surgery. Currently, there are no established disease modifying treatments in regard to the progression of aortic stenosis. The first results about influence of angiotenzin-converting enzyme inhibitors and statins on aortic sclerosis and stenosis progression are promising. Statins are likely to reduce cardiovascular events rather than disease progression, but may be potentially a valuable preventive treatment in these patients. The prejudice against the use of angiotenzin-converting enzyme inhibitors by patients with aortic stenosis is changing. The cautious use of angiotenzin-converting enzyme inhibition by patients with concomitant hypertension, coronary artery disease, and heart failure seems appropriate. Definite evidence from large clinical trials is awaited.

  16. Synthesis and evaluation of chalcone analogues based pyrimidines as angiotensin converting enzyme inhibitors.

    Science.gov (United States)

    Bukhari, S N A; Butt, A M; Amjad, M W B; Ahmad, W; Shah, V H; Trivedi, A R

    2013-11-01

    Hypertension is a widespread and frequently progressive ailment that imparts a foremost threat for cardiovascular and renal disorders. Mammoth efforts are needed for the synthesis of innovative antihypertensive agents to combat this lethal disease. Chalcones have shown antihypertensive activity through inhibition of Angiotensin Converting Enzyme (ACE). Hence, a series of chalcone analogues is synthesized and used as precursor for the synthesis of novel series of pyrimidines. Precursor chalcones were prepared by reacting aldehydes and ketones in presence of sodium hydroxide followed by synthesis of corresponding pyrimidines by reaction with urea in presence of potassium hydroxide. Both groups were then evaluated for their effects on ACE. The results depicted that pyrimidines were more active than chalcones with methoxy (C5 and P5) substitution showing best results to inhibit ACE. Given that chalcone analogues and pyrimidines show a potential as the angiotensin converting enzyme inhibitors.

  17. Advances in angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs).

    Science.gov (United States)

    Swamy, K M K; Lin, Mei-Jung; Sun, Chung-Ming

    2003-09-01

    Hypertension remains one of the most unmet medical needs of this century. While many drugs are available for treating hypertension, efforts are still insufficient to find potent therapeutic agents since cause for hypertension in all patients is not the same. Angiotensin-converting enzyme inhibitors (ACEIs) have emerged as an important class of drugs in the treatment of hypertension, congestive heart failure (CHF), protenuric renal disease, myocardial infarction and stroke. This class of drugs blocks the conversion of angiotensin I to angiotensin II and prevents bradykinin breakdown. However, the lack of specificity of ACEIs leads to the frequent side effects like cough and angio-oedema. Recently developed, specific non-peptide and orally active angiotensin receptor blockers (ARBs) have become the prime therapeutics as they alone or co-administration with ACE inhibitors can control the renin angiotensin disorders. This review explores recent developments in the design, synthesis, and structural modifications of ACE inhibitors as well as angiotensin receptor blockers.

  18. Converting enzyme inhibitor temocaprilat prevents high glucose-mediated suppression of human aortic endothelial cell proliferation.

    Science.gov (United States)

    Yasunari, Kenichi; Maeda, Kensaku; Watanabe, Takanori; Nakamura, Munehiro; Asada, Akira; Yoshikawa, Junichi

    2003-12-01

    We examined the involvement of the oxidative stress in high glucose-induced suppression of human aortic endothelial cell proliferation. Chronic glucose treatment for 72 h concentration-dependently (5.6-22.2 mol/l) inhibited human coronary endothelial cell proliferation. Temocaprilat, an angiotensin-converting enzyme inhibitor, at 10 nmol/l to 1 micromol/l inhibited high glucose (22.2 mmol/l)-mediated suppression of human aortic endothelial cell proliferation. Temocaprilat at 1 micromol/l inhibited high glucose-induced membrane-bound protein kinase C activity in human aortic endothelial cells. The protein kinase C inhibitors calphostin C 100 nmol/l or chelerythrine 1 micromol/l inhibited high glucose-mediated suppression of human aortic endothelial cell proliferation. Chronic high glucose treatment for 72 h increased intracellular oxidative stress, directly measured by flow cytometry using carboxydichlorofluorescein diacetate bis-acetoxymethyl ester, and this increase was significantly suppressed by temocaprilat 10 nmol/l to 1 micromol/l. Bradykinin B2 receptor antagonist icatibant 100 nmol/l significantly reduced the action of temocaprilat; whereas bradykinin B1 receptor antagonist des-Arg9-Leu8-bradykinin 100 nmol/l had no effect. These findings suggest that high glucose inhibits human aortic endothelial cell proliferation and that the angiotensin-converting enzyme inhibitor temocaprilat inhibits high glucose-mediated suppression of human aortic endothelial cell proliferation, possibly through suppression of protein kinase C, bradykinin B2 receptors and oxidative stress.

  19. Proteinuria, a modifiable risk factor: angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs).

    Science.gov (United States)

    Dykeman-Sharpe, Jennifer

    2003-01-01

    Microalbuminuria and proteinuria have been determined to be modifiable risk factors for the progression of chronic kidney disease as well as risk factors for cardiovascular events. Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers have been demonstrated to decrease proteinuria at all stages and slow the progression of renal disease. Proteinuria can be used as a marker of successful treatment in patients with chronic kidney disease in combination with other established targets. This article discusses the various diagnostic tests used for the detection of microalbuminuria and proteinuria and appropriate pharmaceutical treatment.

  20. Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) and lactation: an update.

    Science.gov (United States)

    Shannon, M E; Malecha, S E; Cha, A J

    2000-05-01

    Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are commonly used for the treatment of hypertension. ACEIs have been promoted as first-line therapy for selected patients with chronic hypertension and for the prevention of diabetic nephropathy, thus creating the potential for frequent ACEI exposure among women of childbearing age. ARBs are the most recent addition to the available options for antihypertensive agents. This review specifically focuses on the most up-to-date information regarding these newer antihypertensives with regard to lactation.

  1. Angiotensin-converting enzyme inhibition studies by natural leech inhibitors by capillary electrophoresis and competition assay.

    Science.gov (United States)

    Deloffre, Laurence; Sautiere, Pierre-Eric; Huybrechts, Roger; Hens, Korneel; Vieau, Didier; Salzet, Michel

    2004-06-01

    A protocol to follow the processing of angiotensin I into angiotensin II by rabbit angiotensin-converting enzyme (ACE) and its inhibition by a novel natural antagonist, the leech osmoregulator factor (LORF) using capillary zonal electrophoresis is described. The experiment was carried out using the Beckman PACE system and steps were taken to determine (a) the migration profiles of angiotensin and its yielded peptides, (b) the minimal amount of angiotensin II detected, (c) the use of different electrolytes and (d) the concentration of inhibitor. We demonstrated that LORF (IPEPYVWD), a neuropeptide previously found in leech brain, is able to inhibit rabbit ACE with an IC(50) of 19.8 micro m. Interestingly, its cleavage product, IPEP exhibits an IC(50) of 11.5 micro m. A competition assay using p-benzoylglycylglycylglycine and insect ACE established that LORF and IPEP fragments are natural inhibitors for invertebrate ACE. Fifty-four percent of insect ACE activity is inhibited with 50 micro m IPEP and 35% inhibition with LORF (25 mm). Extending the peptide at both N- and C-terminus (GWEIPEPYVWDES) and the cleavage of IPEP in IP abolished the inhibitory activity of both peptides. Immunocytochemical data obtained with antisera raised against LORF and leech ACE showed a colocalization between the enzyme and its inhibitor in the same neurons. These results showed that capillary zonal electrophoresis is a useful technique for following enzymatic processes with small amounts of products and constitutes the first evidence of a natural ACE inhibitor in invertebrates.

  2. Angiotensin converting enzyme inhibitors and Alzheimer disease in the presence of the apolipoprotein E4 allele.

    Science.gov (United States)

    Qiu, Wendy Wei Qiao; Lai, Angela; Mon, Timothy; Mwamburi, Mkaya; Taylor, Warren; Rosenzweig, James; Kowall, Neil; Stern, Robert; Zhu, Haihao; Steffens, David C

    2014-02-01

    The effect of angiotensin converting enzyme (ACE) inhibitors on Alzheimer disease (AD) remains unclear, with conflicting results reported. We studied the interaction of the Apolipoprotein E (ApoE) genotype and ACE inhibitors on AD. This was a cross-sectional study of homebound elderly with an AD diagnosis and documentation of medications taken. ApoE genotype was determined. A total of 355 subjects with status on ApoE alleles and cognitive diagnoses were studied. The average age (mean ± SD) of this population was 73.3 ± 8.3 years old, and 73% were female. Cross-sectionally, there was no difference in the number of AD cases between ApoE4 carriers and ApoE4 non-carriers or between ACE inhibitor users and non-users in the homebound elderly. ApoE4 carriers treated with ACE inhibitors, however, had more diagnoses of AD compared with those who did not have the treatment (28% versus 6%, p = 0.01) or ApoE4 non-carriers treated with an ACE inhibitor (28% versus 10%, p = 0.03). ACE inhibitor use was associated with AD diagnosis only in the presence of an E4 allele. Using multivariate logistic regression analysis, we found that in diagnosed AD cases there was a significant interaction between ApoE4 and ACE inhibitor use (odds ratio: 20.85; 95% confidence interval: 3.08-140.95; p = 0.002) after adjusting for age, sex, ethnicity, and education. The effects of ACE inhibitors on AD may be different depending on ApoE genotype. A prospective study is needed to determine whether ACE inhibitor use accelerates or poorly delays AD development in ApoE4 carriers compared with ApoE4 non-carriers. Copyright © 2014. Published by Elsevier Inc.

  3. Marketing research on the angiotensin-converting enzyme inhibitors antihypertensive medicines

    Science.gov (United States)

    BOBOIA, ANAMARIA; GRIGORESCU, MARIUS RAREŞ; TURCU - ŞTIOLICĂ, ADINA

    2017-01-01

    Background and aims The research aimed at investigating sales trends of angiotensin-converting enzyme inhibitors antihypertensive medicines, both in terms of quantity and value, in ten community pharmacies, for a period of three years. The research on the antihypertensive medicines consumption is important for highlighting the ever increasing impact of hypertension among the population. Methods The methods used in this research were the following: marketing research, method of sampling, descriptive methods, retrospective analysis, method of comparison. Results The results showed that the drugs containing the active substances of the angiotensin converting enzyme inhibitors class had had significant increases in quantitative and value sales, bringing substantial revenues to pharmacies. From the quantitative perspective, the best-selling products were those containing Enalaprilum, while in terms of value, the best-selling medicines were those containing Perindoprilum. We evidenced that spectacular sales were also achieved for products that have Lisinoprilum, respectively Captoprilum, as active substances. The largest quantities were marketed for the Captopril Terapia® product and the highest earnings were recorded for the Prestarium® medicine. Conclusion This paper approaches an interesting and topical issue, which can be helpful to professionals (pharmacists, doctors) and other categories, such as economists, statisticians, representatives of companies manufacturing medicines, as well as to hypertensive patients, as it could be used to warn population regarding the incidence of cardiovascular diseases, and, at the same time, trace sales trends in order to accomplish profitable business plans. PMID:28246502

  4. FIXED COMBINATION OF THE CALCIUM CHANNEL BLOCKER LERCANIDIPINE AND ANGIOTENSIN CONVERTING ENZYME INHIBITOR ENALAPRIL: POSSIBILITY OF USAGE

    Directory of Open Access Journals (Sweden)

    O. D. Ostroumova

    2013-01-01

    Full Text Available Data on the updated approach to the choice of two-component antihypertensive combinations for different clinical situations are presented. Advantages and indications for combination of an angiotensin converting enzyme (ACE inhibitor and dihydropyridine calcium antagonist are considered. Data on the efficacy and safety of the combination of calcium antagonist of the third generation, lercanidipine, and ACE inhibitor, enalapril, are presented.

  5. Successful pregnancy with scleroderma renal disease and pulmonary hypertension in a patient using angiotensin converting enzyme inhibitors.

    OpenAIRE

    Baethge, B A; Wolf, R E

    1989-01-01

    A patient with scleroderma renal disease and pulmonary hypertension who had a successful pregnancy with the use of angiotensin converting enzyme inhibitors is presented. The routine use of these inhibitors during pregnancy is not recommended, however, owing to the reported potential risks to the fetus.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    Clopidogrel is an oral antiplatelet prodrug, the majority of which is hydrolyzed to an inactive metabolite by hepatic carboxylesterase 1 (CES1). Most angiotensin-converting enzyme inhibitors (ACEIs) are also metabolized by this enzyme. We examined the effects of ACEIs on clopidogrel bioactivation...

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

    Directory of Open Access Journals (Sweden)

    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

  8. The angiotensin converting enzyme inhibitor captopril protects nigrostriatal dopamine neurons in animal models of parkinsonism.

    Science.gov (United States)

    Sonsalla, Patricia K; Coleman, Christal; Wong, Lai-Yoong; Harris, Suzan L; Richardson, Jason R; Gadad, Bharathi S; Li, Wenhao; German, Dwight C

    2013-12-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by a prominent loss of nigrostriatal dopamine (DA) neurons with an accompanying neuroinflammation. The peptide angiotensin II (AngII) plays a role in oxidative-stress induced disorders and is thought to mediate its detrimental actions via activation of AngII AT1 receptors. The brain renin-angiotensin system is implicated in neurodegenerative disorders including PD. Blockade of the angiotensin converting enzyme or AT1 receptors provides protection in acute animal models of parkinsonism. We demonstrate here that treatment of mice with the angiotensin converting enzyme inhibitor captopril protects the striatum from acutely administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrine (MPTP), and that chronic captopril protects the nigral DA cell bodies from degeneration in a progressive rat model of parkinsonism created by the chronic intracerebral infusion of 1-methyl-4-phenylpyridinium (MPP+). The accompanying activation of microglia in the substantia nigra of MPP+-treated rats was reduced by the chronic captopril treatment. These findings indicate that captopril is neuroprotective for nigrostriatal DA neurons in both acute and chronic rodent PD models. Targeting the brain AngII pathway may be a feasible approach to slowing neurodegeneration in PD. © 2013.

  9. [The interaction of the converting-enzyme inhibitor captopril with cardiac glycosides in the rat kidney].

    Science.gov (United States)

    Kuz'min, O B; Tarasov, S V

    1995-01-01

    Strophanthin (0.1 mg.kg, i.v.) and digoxin (0.1 mg/kg, i.v.) moderately increase blood supply of the renal cortical and medullary layers in unconscious rats and enhance renal excretion of sodium and water. Preadministration of the converting enzyme inhibitor captopril (10 mg/kg/day, per os, for 6 days) promoted vascular dilatation in the inner and outer areas of the medulla, which occurred under the action of these agents and substantially increased their natriuretic and diuretic effects. It is concluded that the renin-angiotension system is directly involved into the mechanism of action of cardiac glycosides in the kidneys, acting as a modulator that prevents their vasodilating and tubular effects.

  10. Angiotensin-converting enzyme inhibitor-induced angioedema may not be a class-related event

    Directory of Open Access Journals (Sweden)

    Hassan A Farhat

    2012-09-01

    Full Text Available Angioedema is a rare but potentially life threatening condition commonly associated with angiotensin-converting enzyme inhibitors (ACEIs. The incidence is approximately 0.1- 0.2% and may occur within the first week to several years of taking an ACEI. We present a case of a 37-year-old African-American male who was uneventfully taking a drug combination of quinapril and hydrochlorothiazide. When his medication was changed to lisinopril he developed an acute swelling of his lower lip and chin on fifth dose. The angioedema subsided within 24 hours after discontinuation of lisinopril. Therefore, this suggests that future treatment with ACEIs, as well as angiotensin receptor blockers (ARBs, is not recommended in this type of patient.

  11. The Fetal Safety of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers

    Directory of Open Access Journals (Sweden)

    Myla E. Moretti

    2012-01-01

    Full Text Available Angiotensin converting enzyme (ACE inhibitors and angiotensin II receptor blockers (ARBs are known to cause fetal renal damage in pregnancy. Due to conflicting reports in the literature, their safety after first trimester exposure has been debated. Our aim was to determine whether the use of ACE inhibitors or ARBs in the first trimester of pregnancy is associated with an increased risk for major malformations or other adverse outcomes. All subjects were prospectively enrolled from among women contacting a teratogen information service. At initial contact, details of maternal medical history and exposures were collected and follow-up interviews were conducted to ascertain pregnancy outcomes. Two comparator groups, women with hypertension treated with other antihypertensives, and healthy controls were also recruited. Baseline maternal characteristics were not different among the three groups. There were no differences in rates of major malformations. Both the ACE-ARBs and disease-matched groups exhibited significantly lower birth weight and gestational ages than the healthy controls (P<0.001 for both variables. There was a significantly higher rate of miscarriage noted in the ACE/ARB group (P<0.001. These results suggest that ACE inhibitors/ARBs are not major human teratogens; however, they may be associated with an increased risk for miscarriage.

  12. Prevalence of cough among patients treated with angiotensin converting enzyme inhibitors

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    Gebrehiwot Teklay

    2014-12-01

    Full Text Available Purpose: The aim of this study was to assess the prevalence of cough, its causality and impact on patient adherence in patients taking angiotensin converting enzyme inhibitors. Methods - A cross sectional study was conducted in Ayder Referral Hospital, northern Ethiopia from April to June 2014. Patients who started either captopril or enalapril were interviewed for the occurrence of cough and its characteristics. Data were entered to EPI-info and analyzed using SPSS for windows version 16 statistical software. Logistic regression model was used to analyze variations in occurrence of cough among different factors. P value of less than 0.05 was considered statistically significant. Results - One hundred two patients were participated in this study. Of which, 54(52.9% were females. About half of the respondents (53% were between the ages of 40 to 60. Cough was observed in 30 (29.4% patients. According to World Health Organizations causality scale, the reported cough was certain (drug induced in 5 (7.1% patients; possible in 10 (25% patients; probable in 12 (10.7% patients and unlikely in 3 (57.1% patients. Significant statistical difference was observed between occurrence of cough and durations of treatment (P<0.05. There was no statistically significant difference in occurrence of cough with age, sex, ethnicity, residence, dose and type of ACEI. Conclusion – In this study, dry cough was more prevalent among patients on angiotensin converting enzyme inhibitors. Troublesome cough may affect patient’s sleep and overall adherence to treatment. Health professionals should aware of the characteristics cough and manage accordingly.

  13. Inhibitors of angiotensin-converting enzyme modulate mitosis and gene expression in pancreatic cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, M.K.; Baskaran, K.; Molteni, A. [Northwestern Univ. Medical School, Chicago, IL (United States)

    1995-12-01

    The angiotensin-converting enzyme (ACE) inhibitor captopril inhibits mitosis in several cell types that contain ACE and renin activity. In the present study, we evaluated the effect of the ACE inhibitors captopril and CGS 13945 (10{sup {minus}8} to 10{sup {minus}2}M) on proliferation and gene expression in hamster pancreatic duct carcinoma cells in culture. These cells lack renin and ACE activity. Both ACE inhibitors produced a dose-dependent reduction in tumor cell proliferation within 24 hr. Captopril at a concentration of 0.36 mM and CGS 13945 at 150 {mu}M decreased cellular growth rate to approximately half that of the control. Neither drug influenced the viability or the cell cycle distribution of the tumor cells. Slot blot analysis of mRNA for four genes, proliferation associated cell nuclear antigen (PCNA), K-ras, protein kinase C-{Beta} (PKC-{Beta}) and carbonic anhydrase II (CA II) was performed. Both ACE inhibitors increased K-ras expression by a factor of 2, and had no effect on CA II mRNA levels. Captopril also lowered PCNA by 40% and CGS 13945 lowered PKC-{Beta} gene expression to 30% of the control level. The data demonstrate that ACE inhibitors exhibit antimitotic activity and differential gene modulation in hamster pancreatic duct carcinoma cells. The absence of renin and ACE activity in these cells suggests that the antimitotic action of captopril and CGS 13945 is independent of renin-angiotensin regulation. The growth inhibition may occur through downregulation of growth-related gene expression. 27 refs., 5 figs.

  14. Impact of reference-based pricing for angiotensin-converting enzyme inhibitors on drug utilization.

    Science.gov (United States)

    Schneeweiss, Sebastian; Soumerai, Stephen B; Glynn, Robert J; Maclure, Malcolm; Dormuth, Colin; Walker, Alexander M

    2002-03-19

    Increasing copayments for higher-priced prescription medications has been suggested as a means to help finance drug coverage for elderly patients, but evaluations of the impact of such policies are rare. The objective of this study was to analyze the effect of reference-based pricing of angiotensin-converting enzyme (ACE) inhibitors on drug utilization, cost savings and potential substitution with other medication classes. We analyzed 36 months of claims data from British Columbia for 2 years before and 1 year after implementation of reference-based pricing (in January 1997). The 119,074 patients were community-living Pharmacare beneficiaries 65 years of age or older who used ACE inhibitors during the study period. The main outcomes were changes over time in use of ACE inhibitors, use of antihypertensive drugs and expenditures for antihypertensive drugs, as well as predictors of medication switching related to reference-based pricing. We observed a sharp decline (29%) in the use of higher-priced cost-shared ACE inhibitors immediately after implementation of the policy (p expenditures during its first 12 months. Patients with heart failure or diabetes mellitus who were taking a cost-shared ACE inhibitor were more likely to remain on the same medication after implementation of reference-based pricing (OR 1.12 [95% confidence interval, CI, 1.06-1.19] and 1.28 [95% CI 1.20-1.36] respectively). Patients with low-income status were more likely than those with high-income status to stop all antihypertensive therapy (OR 1.65 [95% CI 1.43-1.89]), which reflects a general trend toward discontinuation of therapy among these patients even before implementation of reference-based pricing. Reference-based pricing in British Columbia achieved a sustained reduction in drug expenditures, and no changes in overall use of antihypertensive therapy were observed. Further research is needed on the overall health and economic effects of such policies.

  15. Association between angiotensin-converting enzyme gene polymorphisms and regression of left ventricular hypertrophy in patients treated with angiotensin-converting enzyme inhibitors.

    Science.gov (United States)

    Kohno, M; Yokokawa, K; Minami, M; Kano, H; Yasunari, K; Hanehira, T; Yoshikawa, J

    1999-05-01

    An insertion/deletion (ID) polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with left ventricular hypertrophy. The present study examined polymorphisms of the ACE gene in patients with essential hypertension and left ventricular hypertrophy who were participants in a long-term trial of therapy with an ACE inhibitor. ACE inhibitor therapy was administered for >2 years to 54 patients with hypertension who had moderate or severe left ventricular hypertrophy. Cardiac dimensions were monitored by echocardiography before the initiation of therapy and after 1 and 2 years of treatment. Serum ACE activity and plasma concentrations of brain natriuretic peptide, a marker for left ventricular hypertrophy, were also monitored. Eighteen patients had the II genotype for the angiotensin-converting enzyme gene, 19 had the ID genotype, and 17 had the DD genotype. Baseline (mean +/- SD) serum ACE activity was significantly greater (P <0.05) in the DD (18 +/- 7 IU/L) group than in the II (7 +/- 4 IU/L) or ID (12 +/- 6 IU/L) groups. ACE inhibitor therapy was effective in controlling blood pressure, and it reduced posterior and septal wall thickness, left ventricular mass index, and plasma brain natriuretic peptide concentration in all three groups. Despite similar blood pressure reductions, after 2 years, mean (+/- SD) regression in posterior wall thickness was significantly less (P <0.05) in the DD group (-9% +/- 5%) than in the ID (-21% +/- 7%) and II (-21% +/- 9%) groups. Similar results were seen for the reductions in brain natriuretic peptide levels. The magnitudes of regression of septal wall thickness and left ventricular mass index during therapy were less in the DD group than the II group (P <0.05). Hypertensive patients with the DD genotype are less likely to have regression of left ventricular hypertrophy when treated with ACE inhibitors than are patients with other ACE genotypes.

  16. Role of angiotensin converting enzyme and angiotensinogen gene polymorphisms in angiotensin converting enzyme inhibitor-mediated antiproteinuric action in type 2 diabetic nephropathy patients.

    Science.gov (United States)

    Aggarwal, Neerja; Kare, Pawan Kumar; Varshney, Parul; Kalra, Om Prakash; Madhu, Sri Venkata; Banerjee, Basu Dev; Yadav, Anil; Raizada, Alpana; Tripathi, Ashok Kumar

    2017-03-15

    To investigate the role of genetic variants of angiotensin converting enzyme (ACE) and angiotensinogen (AGT) genes in the antiproteinuric efficacy of ACE inhibitor therapy in diabetic nephropathy (DN) patients. In the present study, 270 type 2 diabetes mellitus patients with nephropathy were enrolled and treated with ACE inhibitor (ramipril) and followed at 6 mo for renal function and albumin excretion by estimating serum creatinine, end stage renal disease, and albumin/creatinine ratio (ACR) in urine. Genotyping of ACE I/D and AGT M235T polymorphisms were performed by using primer specific polymerase chain reaction (PCR) and PCR-RFLP techniques, respectively. Forty-eight percent of DN patients (responders) benefited with respect to proteinuria from ACE inhibitor therapy at 6 mo follow-up. A significant reduction in ACR was observed after 6 mo treatment with ACE inhibitor irrespective of whether DN patients were micro-albuminuric (≥ 30 and < 300 mg/g creatinine) or macro-albuminuric (≥ 300 mg/g creatinine) at the time of enrollment. However, macro-albuminuric patients (55%) showed better response to therapy. A reduction in urinary ACR was found independent of genotypes of ACE I/D and AGT M235T polymorphisms although macro-albuminuric patients having TT genotype showed statistically insignificant increased response (72%). ACE inhibitor therapy reduced urinary ACR by ≥ 30% in 50% of DN patients and the response is independent of ACE I/D and AGT M235T polymorphisms.

  17. Effect of TNF-alpha--converting enzyme inhibitor on insulin resistance in fructose-fed rats.

    Science.gov (United States)

    Togashi, Nobuhiko; Ura, Nobuyuki; Higashiura, Katsuhiro; Murakami, Hideyuki; Shimamoto, Kazuaki

    2002-02-01

    Insulin resistance is associated with hypertension, obesity, dyslipidemia, and type 2 diabetes. It is well known that tumor necrosis factor (TNF)-alpha is one of the factors linked to obesity-induced insulin resistance; however, there have been no reports on the role of TNF-alpha in insulin resistance in nonobese insulin-resistant hypertensives. We tested the hypothesis that TNF-alpha affects insulin resistance in nonobese insulin-resistant hypertensive fructose-fed rats (FFR) and that a TNF-alpha--converting enzyme (TACE) inhibitor that blocks TNF-alpha secretion improves insulin resistance in FFR. Six-week-old male Sprague-Dawley rats were fed either standard chow (control) or fructose-rich chow (FFR) for 6 weeks. For the last two weeks of a six-week period of either diet, the rats were treated with a vehicle (control or FFR) or a TACE inhibitor (100 mg/kg/d of KB-R7785; FFR+TACE-I) in peritoneal injection. At the age of 12 weeks, insulin sensitivity was assessed in all conscious rats by the euglycemic hyperinsulinemic glucose clamp technique. While FFR had higher blood pressure than the control rats (Pobese models but also in nonobese insulin-resistant models.

  18. Effects of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Contrast-Induced Nephropathy

    Directory of Open Access Journals (Sweden)

    Letian Zhou

    2014-03-01

    Full Text Available Contrast-induced nephropathy (CIN is considered the third leading cause of iatrogenic acute kidney injury in high-risk patients undergoing radiographic procedures. The main mechanism leading to CIN is medullary hypoxia due to decreased renal blood flow, secondary to renal artery vasoconstriction and direct tubular toxicity by contrast medium. Furthermore, experimental data suggests that an activated renin-angiotensin-aldosterone system (RAAS plays a role in the pathophysiology of CIN. However, the role of RAAS blockers, including angiotensin-converting enzyme inhibitors (ACEIs and angiotensin receptor blockers (ARBs in CIN is controversial. They have been reported to be effective in the prevention of CIN in previous studies, but some studies have concluded that they were associated with an increased risk of CIN, especially in patients with pre-existing renal impairment. In summary, there is no solid data to link ACE inhibitors and ARB to CIN, and larger randomised controlled trials are necessary to further investigate their role in the development of CIN. In this review, we discuss the pathophysiology of CIN, the role of RAAS on the development of CIN, and the effect of RAAS blockers on CIN.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2015-12-01

    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.

  1. Effect of angiotensin converting enzyme inhibitor and benzodiazepine intake on bone loss in older Japanese.

    Science.gov (United States)

    Masunari, Naomi; Fujiwara, Saeko; Nakata, Yoshihiro; Furukawa, Kyoji; Kasagi, Fumiyoshi

    2008-03-01

    We investigated the effects of several frequently described medication regimens on annual percentage change in bone mineral density (BMD). A longitudinal cohort study (a retrospective analysis) was conducted. Subjects in the Adult Health Study (a prospective cohort study begun in 1958) have been followed through biennial medical examinations in Hiroshima, Japan. Participants were 2,111 subjects (67% women; aged 47-95 years) who were undergoing biennial health examinations from 1994 to 2000. The subjects were examined for the effect of certain drugs on bone mineral change during baseline and one follow-up (4 year later) measurements. Mean annual percentage change in BMD at the femoral neck was -0.38% for men, and -1.14% for women. After adjustment for sex, age, change of weight, alcohol consumption, and smoking status, annual percentage change in BMD decreased by 0.61% among individuals taking angiotensin converting enzyme (ACE) inhibitors continuously in comparison with individuals who had not taken them (p = 0.002): also decreased 0.40% among individuals taking benzodiazepines (BZDs) continuously (p = 0.034). Our results suggest that careful consideration should be given to the use of ACE inhibitors and BZDs in a cohort of Japanese elderly.

  2. Angiotensin-converting enzyme inhibitor captopril reverses the adverse cardiovascular effects of polymerized hemoglobin.

    Science.gov (United States)

    Li, Tao; Zhou, Ronghua; Yao, Yusheng; Yang, Qian; Zhou, Cheng; Wu, Wei; Li, Qian; You, Zhen; Zhao, Xiaolin; Yang, Linhui; Li, Chen; Zhu, Da; Qiu, Yanhua; Luo, Ming; Tan, Zhaoxia; Li, Huan; Chen, Yanfang; Gong, Gu; Feng, Yuan; Dian, Ke; Liu, Jin

    2014-11-20

    Cell-free hemoglobin-based oxygen carriers (HBOCs) may increase the risk of myocardial infarction and death. We studied the effect of an angiotensin-converting enzyme (ACE) inhibitor on HBOC-induced adverse cardiovascular outcomes and elucidated the underlying mechanisms. With a dog cardiopulmonary bypass model, we demonstrated that a high-dose HBOC (3%, w/v) did not reduce-but aggravated-cardiac ischemia/reperfusion injury. Animals administered a high-dose HBOC experienced coronary artery constriction and depression of cardiac function. Exposure of isolated coronary arteries or human umbilical vein endothelial cells to high-dose HBOC caused impaired endothelium-dependent relaxation, increased endothelial cell necrosis/apoptosis, and elevated NAD(P)H oxidase expression (gp91(phox), p47(phox), p67(phox), and Nox1) and reactive oxygen species (ROS) production. All observed adverse outcomes could be suppressed by the ACE inhibitor captopril (100 μM). Co-incubation with free radical scavenger tempol or NAD(P)H oxidase inhibitor apocynin had no effect on captopril action, suggesting that the positive effects of captopril are ROS- and NAD(P)H oxidase dependent. ACE inhibition by captopril also contributed to these effects. In addition, bioavailable nitrite oxide (NO) reduced by high-dose HBOC was preserved by captopril. Furthermore, HBOC, at concentrations greater than 0.5%, inhibited large conductance Ca(2+)-activated K(+) channel currents in vascular smooth muscle cells in a dose-dependent manner, although captopril failed to improve current activity, providing additional evidence that captopril's effects are mediated by the endothelium, but not by the smooth muscle. Captopril alleviates high-dose HBOC-induced endothelial dysfunction and myocardial toxicity, which is mediated by synergistic depression of NAD(P)H oxidase subunit overproduction and increases in vascular NO bioavailability.

  3. A Meta-analysis of angitensin-converting enzyme inhibitors on normotensive early diabetic renal diseases

    Institute of Scientific and Technical Information of China (English)

    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.

  4. Angiotensin-converting enzyme inhibitors-induced angioedema treated by C1 esterase inhibitor concentrate (Berinert®): about one case and review of the therapeutic arsenal.

    Science.gov (United States)

    Lipski, Samuel Michael; Casimir, Georges; Vanlommel, Martine; Jeanmaire, Mathieu; Dolhen, Pierre

    2015-02-01

    C1 esterase inhibitor (Berinert®) is generally used to treat severe attack of hereditary angioedema. We describe here the case of a patient who presented with a severe angioedema induced by angiotensin-converting enzyme inhibitors (ACEIs) endangering her life. It could be successfully treated with that medicine.

  5. Progression risk, urinary protein excretion, and treatment effects of angiotensin-converting enzyme inhibitors in nondiabetic kidney disease

    DEFF Research Database (Denmark)

    Kent, David M; Jafar, Tazeen H; Hayward, Rodney A;

    2007-01-01

    It is unclear whether patients with nondiabetic kidney disease benefit from angiotensin-converting enzyme inhibitor (ACEI) therapy when they are at low risk for disease progression or when they have low urinary protein excretion. With the use of a combined database from 11 randomized, clinical tr...

  6. Change in prescription pattern as a potential marker for adverse drug reactions of angiotensin converting enzyme inhibitors

    NARCIS (Netherlands)

    Mahmoudpour, Seyed Hamidreza; Asselbergs, Folkert W|info:eu-repo/dai/nl/270752137; de Keyser, Catherine E; Souverein, Patrick C; Hofman, Albert; Stricker, Bruno H; de Boer, Anthonius; Maitland-van der Zee, Anke-Hilse

    2015-01-01

    Background Angiotensin converting enzyme inhibitors (ACEIs) are among the most frequently prescribed groups of medications. ACEI-induced adverse drug reactions (ADRs) are the main reason to discontinue or switch ACEI treatment. ADRs information is not available in prescription databases. Objective T

  7. Comparing the effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on renal function decline in diabetes

    NARCIS (Netherlands)

    Huang, Yunyu; Haaijer-Ruskamp, Flora M.; Voorham, Jaco

    2016-01-01

    Aim: To compare effectiveness of angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs) for protecting Type 2 diabetes mellitus (DM2) patients from renal function decline in a real-world setting. Methods: Retrospective cohort study of new ACEi/ARB users in 2007-2012 in

  8. Change in prescription pattern as a potential marker for adverse drug reactions of angiotensin converting enzyme inhibitors

    NARCIS (Netherlands)

    S.H. Mahmoudpour (Seyed Hamidreza); F.W. Asselbergs (Folkert); C.E. de Keyser (Catherina Elisabeth); P. Souverein (Patrick); A. Hofman (Albert); B.H. Stricker; A.C. de Boer (Anthonius); A-H. Maitland-van der Zee (Anke-Hilse)

    2015-01-01

    textabstractBackground Angiotensin converting enzyme inhibitors (ACEIs) are among the most frequently prescribed groups of medications. ACEI-induced adverse drug reactions (ADRs) are the main reason to discontinue or switch ACEI treatment. ADRs information is not available in prescription databases.

  9. Determinants of angiotensin-converting enzyme inhibitor (ACEI) intolerance and angioedema in the UK Clinical Practice Research Datalink

    NARCIS (Netherlands)

    Mahmoudpour, Seyed Hamidreza; Baranova, Ekaterina Vitalievna; Souverein, Patrick C; Asselbergs, Folkert W|info:eu-repo/dai/nl/270752137; de Boer, Anthonius; Maitland-van der Zee, Anke Hilse

    2016-01-01

    AIM: The aim of the present study was to describe the occurrence and determinants of angiotensin-converting enzyme (ACE) inhibitor (ACEI) intolerance and angioedema (AE) among patients initiating ACEI therapy in a real-world primary care population. METHODS: Two nested case-control studies were cond

  10. Use of angiotensin-converting enzyme inhibitors and freedom from amputation after lower extremity revascularization

    Directory of Open Access Journals (Sweden)

    Kray JE

    2017-07-01

    Full Text Available Jared E Kray,1 Viktor Y Dombrovskiy,2 Todd R Vogel1 1Department of Surgery, Division of Vascular Surgery, School of Medicine, University of Missouri, Columbia, MO, 2Department of Surgery, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA Objective: Angiotensin-converting enzyme inhibitors (ACEIs have not been well evaluated in conjunction with lower extremity revascularization (LER. This study evaluated freedom from amputation in patients who underwent either an open (OPEN or endovascular (ENDO revascularization with and without utilization of an ACEI.Materials and methods: Patients who underwent LER were identified from 2007–2008 Medicare Provider Analysis and Review files. Demographics, comorbidities, and disease severity were obtained. Post-procedural use of an ACEI was confirmed using combining them with National Drug Codes and Part D Files. Outcomes were analyzed using chi-square analysis, Kaplan–Meier test, and Cox regression.Results: We identified 22,954 patients who underwent LER: 8,128 (35.4% patients with claudication, 3,056 (13.3% with rest pain, and 11,770 (51.3% with ulceration or gangrene. More patients underwent ENDO (14,353 than OPEN (8,601 revascularization and 38% of the cohort was taking an ACEI. Overall, ACEI utilization compared to patients not taking ACEI was not associated with lower amputation rates at 30 days (13.5% vs. 12.6%, 90 days (17.7% vs. 17.1%, or 1 year (23.9% vs. 22.8% (P>0.05 for all. After adjustment for comorbidities, ACEI utilization was associated with higher amputation rates for patients with rest pain (hazard ratio: 1.4; 95% confidence interval: 1.1–1.8. Conclusion: ACEI utilization was not associated with overall improved rates of amputation-free survival or overall survival in the vascular surgery population. However, an important finding of this study was that patients presenting with a diagnosis of rest pain and taking an ACEI who underwent a LER had statistically higher

  11. When Should We Start Using Angiotensin Converting Enzyme Inhibitors/Angiotensin Receptor Blockers in Diabetic Kidney Disease?

    Directory of Open Access Journals (Sweden)

    D.D. Ivanov

    2017-03-01

    Full Text Available International guidelines do not recommend angiotensin converting enzyme (ACE inhibitors/angiotensin receptor blockers (ARBs usage in the first stage of diabetic kidney disease. It shows the view, based on a small statistical sample, that olmesartan (or possibly other ACE inhibitors/ARBs should be used to prevent the transition of the first stage of diabetic kidney disease to the second one in type 2 diabetes mellitus.

  12. 2 year followup of patients with diabetes mellitus nephropathy showing albuminuria reversal following angiotensin converting enzyme inhibitors

    OpenAIRE

    Gopinath, S.; B Amirtha Ganesh; Manoj, K; Rubiya,

    2012-01-01

    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, a...

  13. Angiotensin Converting Enzyme Inhibitors Ameliorate Brain Inflammation Associated with Microglial Activation: Possible Implications for Alzheimer's Disease.

    Science.gov (United States)

    Torika, Nofar; Asraf, Keren; Roasso, Ella; Danon, Abraham; Fleisher-Berkovich, Sigal

    2016-12-01

    Angiotensin converting enzyme (ACE) converts Angiotensin I to a potent vasoconstrictor angiotensin II (ANG II). ACE inhibitors (ACEIs) are widely used for the management of hypertension. All components of the renin-angiotensin system (RAS) have also been identified in the brain. In addition to cytokines, neuromodulators such as ANG II can induce neuroinflammation. Moreover, in Alzheimer's disease (AD) models, where neuroinflammation occurs and is thought to contribute to the propagation of the disease, increased levels of ANG II and ACE have been detected. However, the specific effect of ACEIs on neuroinflammation and AD remains obscure. The present study suggests that captopril and perindopril, centrally active ACEIs, may serve as modulators for microglial activation associated with AD. Our in vitro study investigated the effect of both ACEIs on nitric oxide (NO), tumor necrosis factor- α (TNF-α) release and inducible NO synthase (iNOS) expression in lipopolysaccharide (LPS)-induced BV2 microglia. Exposure of BV2 microglia to ACEIs significantly attenuated the LPS-induced NO and TNF-α release. In vivo, short term intranasal administration of perindopril or captopril to 5 Familial AD (5XFAD) mice significantly reduced amyloid burden and CD11b expression (a microglial marker) or only CD11b expression respectively, in the cortex of 5XFAD. Long-term intranasal administration of captopril to mice reduced amyloid burden with no effect on CD11b expression. We provide evidence that intranasal delivery of ACEI may serve as an efficient alternative for their systemic administration, as it results in the attenuation of microglial accumulation and even the reduction of Amyloid β (Aβ) plaques.

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

    Science.gov (United States)

    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.

  15. Angiotensin-converting enzyme inhibitors in the therapy of renal diseases.

    Science.gov (United States)

    Lefebvre, H P; Toutain, P L

    2004-10-01

    Renal diseases, especially chronic renal failure (CRF), are common in canine and feline medicine. The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in these conditions in the development of renal lesions and the progression of kidney dysfunction. Angiotensin-converting enzyme inhibitors (ACEI) are currently considered as the most efficient agents in therapeutic strategies. The benefit of an ACEI treatment can be explained by at least three mechanisms: ACEI limit systemic and glomerular capillary hypertension, have an antiproteinuric effect, and retard the development of glomerulosclerosis and tubulointerstitial lesions. These effects have been studied in dogs and cats, and there is now some evidence to support the recommendation of ACEI therapy in dogs and cats with CRF. Nevertheless the prescription of ACEI in such patients should take into account the potential influence of renal impairment on ACEI disposition, and adverse effects on the renal function itself (especially hypotension and acute reductions in glomerular filtration rate). The risk of drug interaction with diuretics, nonsteroidal anti-inflammatory drugs and anesthetics, should not be overestimated. Furthermore, hypotension may occur in patients on a low sodium diet.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. The angiotensin-converting enzyme inhibitor captopril rescues mice from endotoxin-induced lethal hepatitis.

    Science.gov (United States)

    Ge, Pu; Jiang, Rong; Yao, Xin; Li, Jing; Dai, Jie; Zhang, Li; Ye, Bin

    2017-02-01

    The renin-angiotensin system is classically regarded as a crucial regulator of circulatory homeostasis, but recent studies also revealed its pro-inflammatory roles. The beneficial effects of the angiotensin-converting enzyme inhibitor (ACEI) in severe inflammatory injury in the lung and heart have been previously reported, but its potential effects on lethal hepatitis were unknown. In this study, a mouse model with LPS/d-galactosamine (GalN)-induced fulminant hepatitis were used to test the protective potential of captopril, a representative ACEI. The results indicated that treatment with captopril significantly decreased the plasma level of alanine aminotransferase and aspartate aminotransferase, alleviated the histopathological damage of the liver tissue and improve the survival rate of LPS/GalN-challenged mice. These effects were accompanied by reduced mRNA levels of TNF-α and IL-6 in the liver, and decreased protein level of TNF-α and IL-6 in the plasma. In addition, the activation of caspases 3, 8 and 9, and the presence of TUNEL-positive apoptotic cells, were also suppressed by captopril treatment. The above evidence suggested that the renin-angiotensin system might be involved in the development of LPS/GalN-induced fulminant hepatitis and ACEI might have potential value in lethal hepatitis.

  18. Calcium antagonists and converting enzyme inhibitors reduce renal injury by different mechanisms.

    Science.gov (United States)

    Dworkin, L D; Benstein, J A; Parker, M; Tolbert, E; Feiner, H D

    1993-04-01

    Both glomerular hypertension and hypertrophy have been associated with the development of glomerular injury in models of hypertension and reduced renal mass. The purpose of this study was to examine the effects of antihypertensive therapy on these parameters in the remnant kidney model of progressive glomerular sclerosis. Rats underwent 5/6 nephrectomy and were randomly assigned to receive either no therapy, the calcium entry blocker (CEB), nifedipine, or the angiotensin converting enzyme inhibitor (CEI), enalapril. Administration of either drug was associated with a reduction in systemic blood pressure and in the severity of glomerular injury assessed eight weeks after renal ablation. Micropuncture studies four weeks after ablation revealed that systemic and glomerular capillary pressure were high in untreated remnant kidney rats and reduced by enalapril. Administration of nifedipine was associated with a decline in systemic pressure, however, plasma renin levels increased, causing efferent arteriolar vasoconstriction and persistence of glomerular hypertension. Morphometric analysis showed that kidney weight, glomerular volume and glomerular capillary radius were lower in nifedipine treated rats than in the other two groups, indicating that the CEB, but not enalapril, inhibited the hypertrophic response to ablation of renal mass. Therefore, both CEIs and CEBs reduce glomerular injury in rats with remnant kidneys but they may act by different mechanisms. CEI reduce glomerular capillary pressure while CEBs inhibit compensatory kidney growth.

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

    Science.gov (United States)

    Wan Md Adnan, Wan A H; Zaharan, Nur L; Bennett, Kathleen; Wall, Catherine A

    2011-01-01

    AIMS (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. METHODS The Irish HSE-Primary Care Reimbursement Services database was used to identify patients ≥16 years old co-prescribed ACEIs and ARBs between January 2000 and April 2009 (n= 266 554 prescriptions). The rate of prescribing per 1000 general medical services (GMS) scheme population was calculated for each month. Patients with diabetes, hypertension, heart failure and ischaemic heart disease were also identified by prescribing of certain medications. A linear trend test was used to examine prescribing trends. Logistic regression was used to examine prescribing according to patient characteristics. The effects of the major trials on prescribing were examined using segmented regression analysis for 12 months pre- and post-trials. RESULTS There was a significant linear trend in overall ACEI and ARB co-prescribing over the study period (P ACEIs and ARBs was observed in Ireland during 2000–09. Prescribing patterns did not appear to be affected by results from major trials. PMID:21284706

  20. Pattern of angiotensin-converting enzyme inhibitors induced adverse drug reactions in South Indian teaching hospital

    Directory of Open Access Journals (Sweden)

    Uday Venkat Mateti

    2012-01-01

    Full Text Available Background: Adverse drug reactions (ADRs occur frequently with cardiovascular drugs leading to change in therapy, increasing morbidity, and mortality. Aim: The study was conducted to evaluate the incidence of ADRs due to angiotensin-converting enzyme Inhibitors in cardiology department. Materials and Methods: A cross-sectional observational study was carried out for a period of 6 months. The data were assessed for the pattern of the ADRs with respect to patient demographics, nature of the reaction, outcome of the reactions, causality, severity, and preventability. Results: Among 692 patients, 51 (7.36% had developed 60 ADRs, and majority of cases (56.66% were in the age group of >61 years and most of them were developed in female (80%. The common ADRs observed were cough, hypotension, hyperkalemia, and acute renal failure. In 21.66% cases the dose of the suspected drug was altered and in 78.33% cases the drug was withdrawn. Considering the outcome, 93.33% of cases recovered from ADRs, whereas in 6.66% cases were continuing. Causality assessment showed that majority of ADRs was probable and were found to be moderately severe. Conclusion: Our study concludes geriatrics and female patients have higher incidence of ADRs. So early identification and management of ADRs are essential for this population.

  1. TO THE 110-TH ANNIVERSARY OF RENIN FINDING. FIGHT OF TITANS: ANGIOTENSIN CONVERTING ENZYME INHIBITORS AND SARTANS

    Directory of Open Access Journals (Sweden)

    L. N. Malay

    2009-01-01

    Full Text Available Angiotensin converting enzyme (ACE inhibitors and angiotensin II receptor blockers (ARB slow down progression of cardiovascular diseases and reduce risk of mortality and life threatening complications. What it is better to prescribe for patient in a concrete clinical case – ACE inhibitors or ARB? Authors compare these drug classes (mechanism of action, indications, evidense base of clinical trails, treatment costs and safety. The place of ACE inhibitors and ARB in modern therapy of cardiovascular diseases is defined. Results of the recent trails (ONTARGET, TRANCEND, PRoFESS, I-PRESERVE are discussed.

  2. Hyperkalemia associated with use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.

    Science.gov (United States)

    Raebel, Marsha A

    2012-06-01

    The aims of this article are to review the current understanding of hyperkalemia associated with angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) therapy. This includes reviewing the pathophysiology of how these agents affect potassium handling within the kidney, risk factors for developing hyperkalemia, incidence, clinical signs and symptoms, and providing a practical approach to treatment of the patient who is either at risk of, or experiencing, hyperkalemia. ACEi and ARB are effective therapeutic agents used in a variety of clinical scenarios. However, related to their effects on the renin-angiotensin-aldosterone system, their use can be associated with hyperkalemia, particularly in patients who have chronic renal insufficiency. Published incidence estimates of hyperkalemia associated with ACEi or ARB vary, but up to 10% of patients may experience at least mild hyperkalemia. Important considerations when initiating ACEi or ARB therapy include obtaining an estimate of glomerular filtration rate and a baseline serum potassium concentration, as well as assessing whether the patient has excessive potassium intake from diet, supplements, or drugs that can also increase serum potassium. Serum potassium monitoring shortly after initiation of therapy can assist in preventing hyperkalemia. If hyperkalemia does develop, prompt recognition of cardiac dysrhythmias and effective treatment to antagonize the cardiac effects of potassium, redistribute potassium into cells, and remove excess potassium from the body is important.Understanding the mechanism of action of ACEi and ARB coupled with judicious drug use and clinical vigilance can minimize the risk to the patient of developing hyperkalemia. Should hyperkalemia occur, prompt recognition and management can optimize clinical outcome.

  3. Impairing effects of angiotensin-converting enzyme inhibitor Captopril on bone of normal mice.

    Science.gov (United States)

    Yang, Min; Xia, Chao; Song, Yan; Zhao, Xi; Wong, Man-Sau; Zhang, Yan

    2016-01-15

    There are contradicting results about the effects of angiotensin-converting enzyme inhibitors (ACEIs) on bones. This study was aimed to investigate the effect of ACEI, Captopril, on bone metabolism and histology as well as the action of Captopril on skeletal renin-angiotensin system (RAS) and bradykinin receptor pathway in normal male mice. The urine, serum, tibias and femurs from normal control mice and Captopril-treated (10mg/kg) mice were collected for biochemical, histological and molecular analyses after drug administration for eight weeks. The mice after the treatment with Captopril had a significant decrease of serum testosterone level. The histological measurements showed the loss of trabecular bone mass and trabecular bone number, and the breakage of trabecular bone network as well as the changes of chondrocyte zone at epiphyseal plate in Captopril-treated mice. The defect of Captopril on trabecular bone was reflected by the quantitative bio-parameters from micro-CT. The expression of renin receptor and bradykinin B2 receptor (B2R) was significantly up-regulated in tibia of mice upon to the Captopril treatment, which decreased the ratio of OPG/RANKL and the expression of osteoblastic factor RUNX2. Furthermore, Captopril treatment resulted in the increase of pAkt/Akt and pNFκB expression in tibia. The present study revealed the impairing effects of Captopril on bone via interfering with the circulating sex hormone level and B2R pathway, which suggests that the bone metabolism of patients need to be carefully monitored when being prescribed for ACEIs. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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.

  5. Can Angiotensin-Converting Enzyme Inhibitors Reduce the Incidence, Severity, and Duration of Radiation Proctitis?

    Science.gov (United States)

    Alashkham, Abduelmenem; Paterson, Catherine; Rauchhaus, Petra; Nabi, Ghulam

    2016-01-01

    To determine whether participants taking angiotensin-converting enzyme inhibitors (ACEIs) and treated with radical radiation therapy with neoadjuvant/adjuvant hormone therapy have less incidence, severity, and duration of radiation proctitis. A propensity score analysis of 817 patients who underwent radical radiation therapy with neoadjuvant or adjuvant hormone therapy as primary line management in a cohort study during 2009 to 2013 was conducted. Patients were stratified as follows: group 1, hypertensive patients taking ACEIs (as a study group); group 2, nonhypertensive patients not taking ACEIs; and group 3, hypertensive patients not taking ACEIs (both as control groups). The incidence, severity, and duration of proctitis were the main outcome. χ(2) tests, Mann-Whitney U tests, analysis of variance, risk ratio (RR), confidence interval (CI), Kaplan-Meier plots, and log-rank tests were used. The mean age of the participants was 68.91 years, with a follow-up time of 3.38 years. Based on disease and age-matched comparison, there was a statistically significant difference of proctitis grading between the 3 groups: χ(2) (8, n=308) = 72.52, PACEIs than in nonhypertensive patients not taking ACEIs and hypertensive patients not taking ACEIs (PACEIs was significantly lower than in hypertensive patients not taking ACEIs (RR 0.40, 95% CI 0.30-0.53, PACEIs (RR 0.58, 95% CI 0.44-0.77, PACEIs were significantly different from the control groups (PACEIs had significantly faster resolution of proctitis (PACEIs were significantly less likely to have high-grade proctitis after radical radiation therapy with neoadjuvant or adjuvant hormone therapy (PACEIs was significantly associated with a reduced risk of radiation-induced proctitis and also with acceleration of its resolution. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Safety and efficacy of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in chronic allograft injury

    Directory of Open Access Journals (Sweden)

    P R Shah

    2011-01-01

    Full Text Available Angiotensin II plays a crucial role in the development of chronic allograft injury (CAI. Clinical experience with angiotensin converting enzyme inhibitor (ACEI and angiotensin receptor blockade (ARBS in CAI has unfortunately been limited. We carried out a prospective one year single center case controlled study to analyze the effect of ACEI /ARBS on the progression of CAI and in decreasing proteinuria. One hundred patients with CAI were evaluated. Of the 100 patients, 50 were selected to receive ACEI/ ARBS (group 1 and 50 managed without ACEI/ARBS (group 2. Their remaining management was similar in both the groups. Patients with hyperkalemia, history of allergic reactions, ACEI/ARBS intake and pregnancy were excluded. Average time for development of CAI was 19.6 ± 12.7 months in group 1 vs. 20.8 ± 12.8 in group 2. In group 1, mean systolic/diastolic BP was 136/82 mmHg at the time of establishment of CAI and 124/76 mmHg at the end of one year, and in group 2, it was 138/86 mmHg vs. 126/80 mmHg, respectively. Mean glomerular filtration rate (GFR was 48.78 ± 13.4 in the former vs. 44.23 ± 8.14 in the latter. ACEI/ARBS administration was associated with stabilization of serum creatinine. GFR was maintained up to one year after CAI. Group 1 had a decrease in proteinuria by 1.41 g/day as compared with group 2 with proteinuria of 0.83 g/day. ACEI/ARBS administration is beneficial in CAI for BP control and significant decrease in proteinuria along with the stabilization of graft function.

  7. Use of angiotensin-converting enzyme inhibitors and freedom from amputation after lower extremity revascularization.

    Science.gov (United States)

    Kray, Jared E; Dombrovskiy, Viktor Y; Vogel, Todd R

    2017-01-01

    Angiotensin-converting enzyme inhibitors (ACEIs) have not been well evaluated in conjunction with lower extremity revascularization (LER). This study evaluated freedom from amputation in patients who underwent either an open (OPEN) or endovascular (ENDO) revascularization with and without utilization of an ACEI. Patients who underwent LER were identified from 2007-2008 Medicare Provider Analysis and Review files. Demographics, comorbidities, and disease severity were obtained. Post-procedural use of an ACEI was confirmed using combining them with National Drug Codes and Part D Files. Outcomes were analyzed using chi-square analysis, Kaplan-Meier test, and Cox regression. We identified 22,954 patients who underwent LER: 8,128 (35.4%) patients with claudication, 3,056 (13.3%) with rest pain, and 11,770 (51.3%) with ulceration or gangrene. More patients underwent ENDO (14,353) than OPEN (8,601) revascularization and 38% of the cohort was taking an ACEI. Overall, ACEI utilization compared to patients not taking ACEI was not associated with lower amputation rates at 30 days (13.5% vs. 12.6%), 90 days (17.7% vs. 17.1%), or 1 year (23.9% vs. 22.8%) (P>0.05 for all). After adjustment for comorbidities, ACEI utilization was associated with higher amputation rates for patients with rest pain (hazard ratio: 1.4; 95% confidence interval: 1.1-1.8). ACEI utilization was not associated with overall improved rates of amputation-free survival or overall survival in the vascular surgery population. However, an important finding of this study was that patients presenting with a diagnosis of rest pain and taking an ACEI who underwent a LER had statistically higher amputation rates and a lower amputation-free survival at 1 year. Further analysis is needed to delineate best medical management for patients with critical limb ischemia and taking ACEI who undergo vascular revascularization.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    DEFF Research Database (Denmark)

    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.......4 to 2.5 +/- 0.6 (p attacks were both significantly reduced after 3 months of treatment. These findings support the hypothesis that the combination of verapamil and trandolapril is useful in patients with attenuated left ventricular function...

  10. Angiotensin converting enzyme inhibitor therapy in children with Alport syndrome: effect on urinary albumin, TGF-β, and nitrite excretion

    Directory of Open Access Journals (Sweden)

    Kashtan Clifford E

    2002-02-01

    Full Text Available Abstract Background Angiotensin converting enzyme inhibitors are routinely prescribed to patients with chronic kidney disease because of their known renoprotective effects. We evaluated the effect of short-term therapy with the angiotensin converting enzyme inhibitor, enalapril, in early Alport syndrome, defined as disease duration less than 10 years and a normal glomerular filtration rate. Methods 11 children with early Alport syndrome were investigated. Two consecutive early morning urine specimens were collected at the start of the study for measurement of urinary creatinine, total protein, albumin, TGF-β, and nitrite excretion. Patients were treated with enalapril, ≅ 0.2 mg/kg/day, once a day for 14 days. Two early morning urine specimens were collected on days 13 and 14 of enalapril treatment and two weeks later for measurement of urinary creatinine, total protein, albumin, TGF-β, and nitrite excretion. Results Prior to treatment, urinary excretion of transforming growth factor-β and nitrite, the major metabolite of nitric oxide, was within normal limits in all patients. Administration of enalapril for 2 weeks did not alter urinary albumin, transforming growth factor-β, or nitrite excretion. Conclusion These findings suggest that early Alport syndrome represents a disease involving exclusively intrinsic glomerular barrier dysfunction. At this stage of the illness, there is no evidence of angiotensin II-mediated proteinuria or increased production of transforming growth factor-β and, therefore, routine treatment with an angiotensin converting enzyme inhibitor may not be warranted.

  11. Bioguided isolation of angiotensin-converting enzyme inhibitors from the seeds of Plantago asiatica L.

    Science.gov (United States)

    Geng, Fang; Yang, Li; Chou, Guixin; Wang, Zhengtao

    2010-07-01

    Ethanolic extract of the seeds of Plantago asiatica L. showed significant inhibitory activity of angiotensin-converting enzyme (ACE) determined by monitoring the transformation from a substrate hippuryl-histidyl-leucine (HHL) to the product hippuric acid (HA) in vitro using an UPLC-MS method. The bioguided fractionation of the extract resulted in the isolation of four ACE inhibitory active phenylpropanoid glycosides acteoside, isoacteoside, plantainoside D, and plantamajoside with IC(50) values of 2.69 mM, 2.46 mM, 2.17 mM, and 2.47 mM, respectively. Their structures were elucidated through the analysis of NMR, UV, IR and MS data. Our study is the first demonstration that Plantago asiatica L. and its major constituents have ACE inhibitory activity in vitro. It is assumed that the identified compounds contribute to the angiotensin-converting enzyme-inhibitory activity of the extract.

  12. Milk protein-derived peptide inhibitors of angiotensin-I-converting enzyme

    OpenAIRE

    Fitzgerald, Richard J; Meisel, Hans

    2000-01-01

    peer-reviewed Numerous casein and whey protein-derived angiotensin-I-converting enzyme (ACE) inhibitory peptides/hydrolysates have been identified. Clinical trials in hypertensive animals and humans show that these peptides/hydrolysates can bring about a significant reduction in hypertension. These peptides/hydrolysates may be classified as functional food ingredients and nutraceuticals due to their ability to provide health benefits i.e. as functional food ingredients in reduc...

  13. Angiotensin converting enzyme inhibitors and the reduced risk of Alzheimer's disease in the absence of apolipoprotein E4 allele.

    Science.gov (United States)

    Qiu, Wei Qiao; Mwamburi, Mkaya; Besser, Lilah M; Zhu, Haihao; Li, Huajie; Wallack, Max; Phillips, Leslie; Qiao, Liyan; Budson, Andrew E; Stern, Robert; Kowall, Neil

    2013-01-01

    Our cross-sectional study showed that the interaction between apolipoprotein E4 (ApoE4) and angiotensin converting enzyme (ACE) inhibitors was associated with Alzheimer's disease (AD). The aim of this longitudinal study was to differentiate whether ACE inhibitors accelerate or reduce the risk of AD in the context of ApoE alleles. Using the longitudinal data from the National Alzheimer's Coordinating Center (NACC) with ApoE genotyping and documentation of ACE inhibitors use, we found that in the absence of ApoE4, subjects who had been taking central ACE inhibitor use (χ2 test: 21% versus 27%, p = 0.0002) or peripheral ACE inhibitor use (χ2 test: 13% versus 27%, p ApoE4, there was no such association between ACE inhibitor use and the risk of AD. After adjusting for the confounders, central ACE inhibitor use (OR = 0.68, 95% CI = 0.55, 0.83, p = 0.0002) or peripheral ACE inhibitor use (OR = 0.33, 95% CI = 0.33, 0.68, p ApoE4 non-carriers. In conclusion, ACE inhibitors, especially peripherally acting ones, were associated with a reduced risk of AD in the absence of ApoE4, but had no such effect in those carrying the ApoE4 allele. A double-blind clinical trial should be considered to determine the effect of ACE inhibitors on prevention of AD in the context of ApoE genotype.

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

    Directory of Open Access Journals (Sweden)

    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

  15. Angiotensine converting enzyme inhibitors In acute myocardial infarction--a review.

    Science.gov (United States)

    Sawhney, J P S

    2011-01-01

    Coronary artery diseases (CADs) are preventable and controllable disorders, but they continue to be a major cause of morbidity and premature mortality across globe. India is projected to have 62 million CAD patients by 2015, with nearly 1/3rd of this burden shared by patients younger than 40 years. The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in blood pressure (BP) regulation and fluid and electrolyte homoeostasis. Activation of RAAS has long been implicated in the pathogenesis of acute myocardial infarction (AMI) and benefits of inhibition of RAAS as an effective way to intervene in the pathogenesis of AMI is well documented. In the setting of AMI, angiotensin-II plays a significant detrimental role, contributing to cardiac remodeling, a process that predisposes to subsequent arrhythmia and cardiac failure. Angiotensin converting enzyme inhibitors (ACEls) play a key role in the clinical management of several cardiovascular disease (CVD)s such as AMI, by inhibiting the actions of angiotensin-II, ACEIs would be expected to modify unwanted post-AMI events. ACEIs trials have tested AMI patients with two different approaches: selective (those with left ventricular dysfunction (LVD) treated over a long-term) and relatively unselective (those treated early over the course and for a short-period, up to 6 weeks). In general, results are consistent and beneficial as regards to reduction in both short-term & long-term mortality and heart failure. There are evidences that suggest yielding of an extra protection (reduced mortality and occurrence of severe LVD) with early introduction of ACEIs in the course of AMI. Trials have also shown ACEIs effective and consistent protection against re-infarction and management of arrhythmias after AMI. Large clinical trials have proven ACEIs to be superior to ARB, in preventing CV deaths in high-risk AMI subjects. They have proven to be safe & effective in diabetic & older population. With wealth of evidence

  16. Angiotensin converting enzyme inhibitors effect on endothelial dysfunction: a meta-analysis of randomised controlled trials.

    Science.gov (United States)

    Shahin, Yousef; Khan, Junaid Alam; Samuel, Nehemiah; Chetter, Ian

    2011-05-01

    Several studies have assessed the effect of angiotensin converting enzyme inhibitors (ACEIs) on endothelial dysfunction as measured by brachial flow-mediated vasodilatation (FMD). We conducted a meta-analysis to investigate this effect in comparison to placebo or no treatment and to other antihypertensive agents. MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from 1996 to October 2010 on randomised controlled trials (RCTs) that assessed the effect of ACEIs on brachial FMD versus placebo or no treatment and ACEIs versus angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs) and β-blockers. Data from included studies were pooled with use of random effects meta-analysis of the weighted mean change differences between the comparator groups. Heterogeneity across studies was assessed with the I(2) statistic. In 10 trials including 1129 patients, treatment with ACEIs (n = 498) versus placebo or no treatment (n = 503) significantly improved brachial FMD (pooled mean change difference 1.26%, 95% C.I. 0.46-2.07, p = 0.002 with significant heterogeneity). In 11 trials which included 805 patients, treatment with ACEIs (n = 264) had a significant effect on brachial FMD when compared with other antihypertensives (ARBs, CCBs and β-blockers) (n = 420) (pooled mean change difference 0.89%, 95% C.I. 0.22-1.56, p = 0.009, I(2) = 83%, p for heterogeneity ACEIs had no significant effect on FMD when compared with ARBs (pooled mean change difference = 0.21%, 95% C.I. -0.24 to 0.66, p = 0.36, I(2) = 0%). However, in 4 trials ACEIs significantly improved FMD when compared with CCBs (pooled mean change difference 2.15%, 95% C.I. 0.55-3.75, p = 0.009, I(2) = 90%, p for heterogeneity ACEIs also had a significant effect on FMD (pooled mean change difference = 0.59%, 95% C.I. 0.05-1.13, p = 0.03, I(2) = 34%, p for heterogeneity = 0.21). This study shows that ACEIs improve brachial FMD which is a marker of endothelial function in

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. Angiotensin-Converting Enzyme Inhibitors' Influence on Antiplatelet Therapy of Clopidogrel in ACS.

    Science.gov (United States)

    Yang, Shuo; Cui, Chanjuan; Zhang, Jie; Qiao, Rui

    2016-10-01

    Clopidogrel is a prodrug, the minority of which is converted to an active metabolite by hepatic cytochrome P450 (CYP2C19), however, most of it is metabolized to inactive substance by hepatic carboxylesterase1 (CES1). Meanwhile angiotensin-converting enzyme inhibitors (ACEIs) are mostly metabolized by CES1. We aimed to assess the impact of ACEIs on platelet inhibition by clopidogrel. We genotyped variants CES1, CYP2C19*2 and *3 in 502 patients with acute coronary syndrome (ACS) receiving clopidogrel therapy, and analyzed the effects of ACEIs on responsiveness to clopidogrel by the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay and ADP-stimulated impedance whole blood platelet aggregation assay. It showed that the allele frequency of CES1 c.428A was 0% in these patients. 45.22% (227/502) of these patients were carriers of CYP2C19*2 or CYP2C9*3 loss-of-function alleles. Among them, 57.71% (131/227) of the patients with CYP2C19 variants received ACEIs therapy. In a total of 502 patients, there was no difference in the VASP-PRI or the impedance whole blood platelet aggregation assay between the ACEIs group and non-ACEIs group [56.26 ± 14.55% versus 57.76 ± 13.56%, p = 0.241; 0 (0 - 2) Ω vs. 0 (0 - 2) Ω, p = 0.856]. In the CYP2C19 variant patients, there was no difference in the VASP-PRI or the impedance whole blood platelet aggregation assay between ACEIs group and non-ACEIs group [57.24 ± 15.12% versus 58.07 ± 13.90%, p = 0.667; 0 (0 - 2) Ω versus 0 (0 - 2) Ω, p = 0.536]. In the subgroups of ACS patients (unstable angina, non-ST-segment elevation myocardial infarction, ST-segment elevation myocardial infarction), there was no difference in the VASP-PRI between the ACEIs group and non-ACEIs group [55.81 ± 15.24% versus 58.37 ± 13.31%, p = 0.103; 55.76 ± 15.20% versus 49.09 ± 15.22%, p = 0.098; 58.13 ± 11.48% versus 61.87 ± 10.34%, p = 0.221], and there was no difference in the impedance whole blood platelet aggregation assay between

  19. Paracrine systems in the cardioprotective effect of angiotensin-converting enzyme inhibitors on myocardial ischemia/reperfusion injury in rats.

    Science.gov (United States)

    Liu, Y H; Yang, X P; Sharov, V G; Sigmon, D H; Sabbath, H N; Carretero, O A

    1996-01-01

    After transient episodes of ischemia, benefits of thrombolytic or angioplastic therapy may be limited by reperfusion injury. Angiotensin-converting enzyme inhibitors protect the heart against ischemia/reperfusion injury, an effect mediated by kinins. We examined whether the protective effect of the angiotensin-converting enzyme inhibitor ramiprilat on myocardial ischemia/reperfusion is due to kinin stimulation of prostaglandin and/or nitric oxide release. The left anterior descending coronary artery of Lewis inbred rats was occluded for 30 minutes, followed by 120 minutes of reperfusion. Immediately before reperfusion rats were treated with vehicle, ramiprilat, or the angiotensin II type 1 receptor antagonist losartan. We tested whether pretreatment with the kinin receptor antagonist Hoe 140, the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester, or the cyclooxygenase inhibitor indomethacin blocked the effect of ramiprilat on infarct size and reperfusion arrhythmias. In controls, infarct size as a percentage of the area at risk was 79 +/- 3%; ramiprilat reduced this to 49 +/- 4% (P < .001), but losartan had little effect (74 +/- 6%, P = NS). Pretreatment with Hoe 140, NG-nitro-L-arginine methyl ester, or indomethacin abolished the beneficial effect of ramiprilat. Compared with the 30-minute ischemia/120-minute reperfusion group, nonreperfused hearts with 30 minutes of ischemia had significantly smaller infarct size as a percentage of the area at risk, whereas in the 150-minute ischemia group it was significantly larger. This suggests that reperfusion caused a significant part of the myocardial injury, but it also suggests that compared with prolonged ischemia, reperfusion salvaged some of the myocardium. Ventricular arrhythmias mirrored the changes in infarct size. Thus, angiotensin-converting enzyme inhibitors protect the myocardium against ischemia/reperfusion injury and arrhythmias; these beneficial effects are mediated primarily by a kinin

  20. Angiotensin-converting enzyme inhibitors reduce oxidative stress intensity in hyperglicemic conditions in rats independently from bradykinin receptor inhibitors

    Science.gov (United States)

    Mikrut, Kinga; Kupsz, Justyna; Koźlik, Jacek; Krauss, Hanna; Pruszyńska-Oszmałek, Ewa; Gibas-Dorna, Magdalena

    2016-01-01

    Aim To investigate whether bradykinin-independent antioxidative effects of angiotensin-converting enzyme inhibitors (ACEIs) exist in acute hyperglycemia. Methods Male Wistar rats were divided into the normoglycemic group (n = 40) and the hyperglycemic group (n = 40). Hyperglycemia was induced by a single intraperitoneal injection of streptozotocin (STZ, 65 mg/kg body weight) dissolved in 0.1 mol/L citrate buffer (pH 4.5) 72 hours before sacrifice. The normoglycemic group received the same volume of citrate buffer. Each group was divided into five subgroups (n = 8): control group, captopril group, captopril + bradykinin B1 and B2 receptor antagonists group, enalapril group, and enalapril + bradykinin B1 and B2 receptor antagonists group. Captopril, enalapril, B1 and B2 receptor antagonists, or 0.15 mol/L NaCl were given at 2 and 1 hour before sacrifice. Oxidative status was determined by measuring the concentration of malondialdehyde and H2O2, and the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Results In STZ-induced hyperglycemic rats ACEIs significantly reduced H2O2 and MDA concentration, while they significantly enhanced SOD and GPx activity. The hyperglycemic group treated simultaneously with ACEIs and bradykinin B1 and B2 receptor antagonists showed a significant decrease in H2O2 concentration compared to the control hyperglycemic group. Conclusion These results suggest the existence of additional antioxidative effect of ACEIs in hyperglycemic conditions, which is not related to the bradykinin mediation and the structure of the drug molecule. PMID:27586552

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

    DEFF Research Database (Denmark)

    Hermanrud, Thorbjørn; Duus, Nicolaj; Bygum, Anette

    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...

  2. 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

    DEFF Research Database (Denmark)

    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...... myocardial infarctions confirmed by enzyme studies. A total of 2606 patients had echocardiographic evidence of left ventricular systolic dysfunction (ejection fraction,

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

    DEFF Research Database (Denmark)

    Gislason, Gunnar H; Rasmussen, Jeppe N; 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...

  4. The toxicity of angiotensin converting enzyme inhibitors to larvae of the disease vectors Aedes aegypti and Anopheles gambiae.

    Science.gov (United States)

    Abu Hasan, Zatul-'Iffah; Williams, Helen; Ismail, Nur M; Othman, Hidayatulfathi; Cozier, Gyles E; Acharya, K Ravi; Isaac, R Elwyn

    2017-03-27

    The control of mosquitoes is threatened by the appearance of insecticide resistance and therefore new control chemicals are urgently required. Here we show that inhibitors of mosquito peptidyl dipeptidase, a peptidase related to mammalian angiotensin-converting enzyme (ACE), are insecticidal to larvae of the mosquitoes, Aedes aegypti and Anopheles gambiae. ACE inhibitors (captopril, fosinopril and fosinoprilat) and two peptides (trypsin-modulating oostatic factor/TMOF and a bradykinin-potentiating peptide, BPP-12b) were all inhibitors of the larval ACE activity of both mosquitoes. Two inhibitors, captopril and fosinopril (a pro-drug ester of fosinoprilat), were tested for larvicidal activity. Within 24 h captopril had killed >90% of the early instars of both species with 3(rd) instars showing greater resistance. Mortality was also high within 24 h of exposure of 1(st), 2(nd) and 3(rd) instars of An. gambiae to fosinopril. Fosinopril was also toxic to Ae. aegypti larvae, although the 1(st) instars appeared to be less susceptible to this pro-drug even after 72 h exposure. Homology models of the larval An. gambiae ACE proteins (AnoACE2 and AnoACE3) reveal structural differences compared to human ACE, suggesting that structure-based drug design offers a fruitful approach to the development of selective inhibitors of mosquito ACE enzymes as novel larvicides.

  5. Angiotensin-converting enzyme

    DEFF Research Database (Denmark)

    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...

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

    DEFF Research Database (Denmark)

    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....

  7. Effects of nabumetone, celecoxib, and ibuprofen on blood pressure control in hypertensive patients on angiotensin converting enzyme inhibitors.

    Science.gov (United States)

    Palmer, Robert; Weiss, Robert; Zusman, Randall M; Haig, Ann; Flavin, Susan; MacDonald, Brian

    2003-02-01

    Nonsteroidal anti-inflammatory drugs interfere with certain antihypertensive therapies. In a double-blind study, 385 hypertensive patients stabilized on an angiotensin converting enzyme inhibitor were treated with nabumetone, celecoxib, ibuprofen, or placebo for 4 weeks. Ibuprofen caused significantly greater increases in systolic (P nabumetone or celecoxib. The proportion of patients with systolic BP increases of clinical concern at end point was significantly higher (P nabumetone group (5.5%; 5 of 91) or the celecoxib group (4.6%; 4 of 87) compared to the placebo group (1.1%; 1 of 91).

  8. Screening of Zulu medicinal plants for angiotensin converting enzyme (ACE) inhibitors.

    Science.gov (United States)

    Duncan, A C; Jäger, A K; van Staden, J

    1999-12-15

    Twenty plants used by traditional healers in South Africa for the treatment of high blood pressure were investigated for their anti-hypertensive properties, utilizing the angiotensin converting enzyme assay. A hit rate of 65% was achieved, with the highest inhibition (97%) obtained by Adenopodia spicata leaves. A further seven plants exhibited an inhibition greater than 70% and five more over 50%. The leaves of the plants showed the greatest levels of inhibition. There was little difference in the overall hit rate between ethanolic and aqueous extracts, although in most cases there was a marked difference in activity between aqueous and ethanolic extracts from the same species. Plants exhibiting inhibition levels greater than 50% were further tested for the presence of tannins in order to eliminate possible false positives. Active plants that did not contain tannins were Agapanthus africanus, Agave americana, Clausena anisata, Dietes iridioides, Mesembruanthemum spp., Stangeria eriopus and Tulbaghia violacea.

  9. A focused parameter update: hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema.

    Science.gov (United States)

    Zuraw, Bruce L; Bernstein, Jonathan A; Lang, David M; Craig, Timothy; Dreyfus, David; Hsieh, Fred; Khan, David; Sheikh, Javed; Weldon, David; Bernstein, David I; Blessing-Moore, Joann; Cox, Linda; Nicklas, Richard A; Oppenheimer, John; Portnoy, Jay M; Randolph, Christopher R; Schuller, Diane E; Spector, Sheldon L; Tilles, Stephen A; Wallace, Dana

    2013-06-01

    These parameters were developed by the Joint Task Force on Practice Parameters (JTFPP), representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma and Immunology. The AAAAI and the ACAAI have jointly accepted responsibility for establishing "A focused parameter update: Hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the JTFPP, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. The Joint Task Force on Practice Parameters understands that the cost of diagnostic tests and therapeutic agents is an important concern that might appropriately influence the work-up and treatment chosen for a given patient. The JTFPP recognizes that the emphasis of our primary recommendations regarding a medication might vary, for example, depending on third-party payer issues and product patent expiration dates. However, because the cost of a given test or agent is so widely variable and there is a paucity of pharmacoeconomic data, the JTFPP generally does not consider cost when formulating practice parameter recommendations. In some instances the cost benefit of an intervention is considered relevant, and commentary might be provided. These parameters are not designed for use by pharmaceutical companies in drug promotion

  10. Mixed inhibitors of angiotensin-converting enzyme and enkephalinase: Rational design, properties, and potential cardiovascular applications of glycopril and alatriopril

    Energy Technology Data Exchange (ETDEWEB)

    Gros, C.; Noel, N.; Souque, A.; Schwartz, J.C. (Inst. National de la Sante et de la Recherche Medicale, Paris (France)); Danvy, D.; Plaquevent, J.C.; Duhamel, L.; Duhamel, P. (Univ. de Rouen, Mont Saint Aignan (France)); Lecomte, J.M. (Lab. Bioprojet, Paris (France)); Bralet, J. (Lab. de Pharmacodynamie, Dijon (France))

    1991-05-15

    Angiotensin-converting enzyme (ACE) and enkephalinase, two cell surface metallopeptidases, are responsible for angiotensin II formation and atrial natriuretic factor (ANF) degradation, respectively, and thereby play a critical role in the metabolism of hormonal peptides exerting essentially opposite actions in cardiovascular regulations. To affect simultaneously both hormonal systems by a single molecular structure, the authors designed glycoprilat and alatrioprilat {l brace}(S)-N-(3-(3,4-methylenedioxyphenyl)-2-(mercaptomethyl)-1-oxopropyl)glycine and -alanine, respectively{r brace}. In vitro the two compounds inhibit both ACE and enkephalinase activities with similar, nanomolar potencies, and in vivo, glycopril and alatriopril, the corresponding diester prodrugs, occupy the two enzyme molecules in lung at similar low dosages. The high potency of these compounds is attributable to interaction of the methylenedioxy group with the S{sub 1} subsite of ACE and of the aromatic ring with the S{prime}{sub 1} subsite of enkephalinase. In rodents, low doses of these mixed inhibitors exert typical actions of ACE inhibitors--i.e., prevention of angiotensin I-induced hypertension-as well as of enkephalinase inhibitors--i.e., protection from {sup 125}I-ANF degradation or enhancement of diuresis and natriuresis following acute extracellular volume expansion. In view of the known counterbalanced physiological actions of the two hormonal peptides, whose metabolism is controlled by ACE and enkephalinase, mixed inhibitors of the two peptidases show promise for the treatment of various cardiovascular and salt-retention disorders.

  11. Reduction of microalbuminuria in type-2 diabetes mellitus with angiotensin-converting enzyme inhibitor alone and with cilnidipine.

    Science.gov (United States)

    Singh, V K; Mishra, A; Gupta, K K; Misra, R; Patel, M L; Shilpa

    2015-01-01

    The aim of our study was to find out the antiproteinuric effect of enalapril angiotensin-converting enzyme (ACE inhibitor) alone or in combination with cilnidipine in patients with type-2 diabetes mellitus. The study was conducted on 71 patients with type-2 diabetes mellitus patients with hypertension and microalbuminuria. They were divided into two groups randomly as follows: Group I (enalaprilalone, n = 36) and Group II (enalapril with cilnidipine, n = 35). In both the groups, baseline 24 h urinary albumin was estimated and was repeated every 3 months upto 1-year. After 1-year follow-up, reduction in microalbuminuria was found to be greater in Group II. In Group I microalbuminuria came down by 25.68 ± 21.40 while in Group II it reduced by 54.88 ± 13.84 (P microalbuminuria reduction over and above the well-proven effect of ACE inhibitors.

  12. The Effect of Aspirin on Angiotensin Converting Enzyme Inhibitors-Induced Cough : A Double Blind Clinical Trial

    Directory of Open Access Journals (Sweden)

    A Esmaeili Nadimi

    2005-03-01

    Full Text Available Background: Dry cough is the most common adverse effect and limiting factor of all angiotensin converting-enzyme inhibitors (ACEIs . Prostaglandins have been pinpointed as playing an important role in the genesis of this problem. This double blind clinical trial desinged to study the efficacy of 500 milligram(mg of aspirin comparing with placebo in controlling Enalapril-induced cough. Methods: The subjects were 32 patients who had developed Enalapril-induced cough.They were randomized into two groups: a group of daily dose of aspirin, 500 mg and a group of placebo for a treatment period of 4 weeks. Mean of cough severity was compared between two groups before treatment and weekly, until 4 weeks. Results: Mean of cough severity in aspirin and placebo groups before and at the end of first week of treatment did not show any significant difference. After the second ,third, and fourth weeks, cough severity scores were significantly reduced in aspirin group(p<0.001. Conclusion: 500mg aspirin, once daily, can suppress or abolish Enalapril-induced cough and this finding proposes alternative therapeutic approach for ACEIs-induced related cough. Keywords: aspirin, cough, Angiotensin-Converting Enzyme Inhibitors (ACEIs, enalapril

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Thorbjørn Hermanrud

    2016-01-01

    Full Text Available 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.

  16. Angiotensin I-converting enzyme inhibitor derived from cross-linked oyster protein.

    Science.gov (United States)

    Xie, Cheng-Liang; Kim, Jin-Soo; Ha, Jong-Myung; Choung, Se-Young; Choi, Yeung-Joon

    2014-01-01

    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.

  17. Angiotensin I-Converting Enzyme Inhibitor Derived from Cross-Linked Oyster Protein

    Directory of Open Access Journals (Sweden)

    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.

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

    DEFF Research Database (Denmark)

    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...

  19. Early genes induction in spontaneously hypertensive rats left ventricle with angiotensin-converting enzyme inhibitors but not hydralazine

    Energy Technology Data Exchange (ETDEWEB)

    Susic, D.; Aristizabal, D.J.; Prakash, O.; Nunez, E.; Frohlich, E.D. [Hypertension Research Laboratories, New Orleans, LA (United States)

    1995-12-01

    Spontaneously hypertensive rats were given an angiotensin-converting enzyme (ACE) inhibitor (benazepril or quinapril) or hydralazine and were left for up to 6 hr. To examine whether administration of antihypertensive agents affects expression of immediate early genes in left ventricular myocardium, groups of rats were sacrificed at 1, 3, and 6 hr after dosing; total RNA was extracted from left ventricular tissue and analyzed by blot hybridization technique using labeled probes for c-myc, c-fos, and GAPDH mRNA. All three antihypertensive agents reduced pressure similarly, and treatment with the two ACE inhibitors increased c-fos and c-myc mRNA expression in left ventriculum. By contrast, hydralazine did not increase steady-state mRNA expression of either proto-oncogene. Thus, in parallel with the pressure fall, acute administration of the ACE inhibitors induced expression of c-fos and c-myc mRNAs in the left ventricle. Since the equidepressor dose of hyralazine did not affect expression of these proto-oncogenes, this effect of ACE inhibitors is independent of their hemodynamic action. 27 refs., 1 fig., 2 tabs.

  20. 2 year followup of patients with diabetes mellitus nephropathy showing albuminuria reversal following angiotensin converting enzyme inhibitors

    Directory of Open Access Journals (Sweden)

    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.

  1. Involvement of Renin-Angiotensin System in Damage of Angiotensin-Converting Enzyme Inhibitor Captopril on Bone of Normal Mice.

    Science.gov (United States)

    Liu, Jin-Xin; Wang, Liang; Zhang, Yan

    2015-01-01

    This study was performed to investigate the effect of angiotensin-converting enzyme inhibitor, captopril, on bone metabolism and histology, and the action of captopril on the components of the skeletal renin-angiotensin system (RAS) and bradykinin receptor in normal male mice. The mice were orally administered captopril (10 mg/kg) for 4 weeks with vehicle-treated mice as normal control. The histology of trabecular bone at the distal femoral end was determined by hematoxylin & eosin, Safranin O and Masson-Trichrome staining. The captopril-treated mice showed a decreased level of testosterone (pCaptopril has detrimental effects on trabecular bone as demonstrated by the loss of cancellous bone mass and network connections as well as changes to the chondrocytes zone. The expression of angiotensin-converting enzyme (pcaptopril treatment. Thus, the potential underlying mechanism of the damage of captopril on bone can be attributed the increased activity of local bone RAS and the activation of bradykinin receptor.

  2. Long-term Administration of Angiotension-Converting Enzyme Inhibitor Improves the Outcome of Chronic Heart Failure in Senile Patients

    Institute of Scientific and Technical Information of China (English)

    陈学林; 张劲农; 柯琴梅; 张银环; 刘承云

    2002-01-01

    Summary: One hundred and sixteen senile patients (older than 65 years) with chronic heart failure (CHF) were analyzed retrospectively in order to verify if old patients with CHF would benefit from long-term (one year) angiotension-converting enzyme inhibitor (ACEI) treatment. The frequency of drugs (including ACEI, digitalis and diuretic) used was stratified into four degrees accordingly. Development of the CHF was scored with regard to relapse rate and severity of this disease. Stepwise regression analysis was applied to explore the relationship between the scored outcome of CHF and the frequency of individual drug administra tion. A significant relationship of the scored outcome of CHF to the frequency of ACEI usage but not to digitalis nor to diuretics was found (partial coefficient of the correlation r=0. 42, P=0. 002). It was concluded that the longterm administration of ACEI improves the outcome of CHF in senile patients.

  3. Synthesis and evaluation of novel triazoles and mannich bases functionalized 1,4-dihydropyridine as angiotensin converting enzyme (ACE) inhibitors.

    Science.gov (United States)

    Kumbhare, Ravindra M; Kosurkar, Umesh B; Bagul, Pankaj K; Kanwal, Abhinav; Appalanaidu, K; Dadmal, Tulshiram L; Banerjee, Sanjay Kumar

    2014-11-01

    A series of novel diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate embedded triazole and mannich bases were synthesized, and evaluated for their angiotensin converting enzyme (ACE) inhibitory activity. Screening of above synthesized compounds for ACE inhibition showed that triazoles functionalized compounds have better ACE inhibitory activity compared to that of mannich bases analogues. Among all triazoles we found 6 h, 6 i and 6 j to have good ACE inhibition activity with IC50 values 0.713 μM, 0.409 μM and 0.653 μM, respectively. Among mannich bases series compounds, only 7c resulted as most active ACE inhibitor with IC50 value of 0.928 μM.

  4. Effect of Angiotensin-Converting Enzyme Inhibitors on Physical Function in Elderly Subjects: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Zhou, Ling-shan; Xu, Ling-jie; Wang, Xue-qing; Huang, Yi-huan; Xiao, Qian

    2015-09-01

    Sarcopenia has been accepted as a new geriatric syndrome, which will become a common and important public health challenge. And angiotensin-converting enzyme inhibitors (ACEIs) have been shown to improve exercise capacity in elderly without heart failure. To evaluate the effect of angiotensin-converting enzyme inhibitors (ACEIs) on physical function in elderly. The Cochrane Library, PubMed, EMBASE and Web of Science were searched. All researches included were randomized controlled trials (RCTs) which compared any kind of ACEIs with placebo or other anti-hypertensives in elderly, and provided empirical data of grip strength and 6-min walk distance change from baseline. Risk of bias was systematically assessed by using the Cochrane risk of bias tool. Data of grip strength and 6-min walk distance change from baseline were collected and mean differences (MDs) were calculated along with 95% CI (confidence interval) by using a random effects model. In 3 RCTs including 337 elderly participants, ACEIs (n = 178) did not significantly improved 6-min walk distance (13.45, 95% CI: -16.71 to 43.61; P = 0.38) versus placebo or other antihypertensives (n = 159). In 3 RCTs including 499 elderly participants, grip strength was not significantly different (-0.67, 95% CI: -1.53 to 0.19; P = 0.12) between ACEIs (n = 260) and placebo or other antihypertensives (n = 239). There exists only 4 RCTs and the number of participants is limited. Pooling of data were from different trials including different participant characteristics. And intervention is not strictly consistent. This study shows that ACEIs can not significantly improve walk distance or the age-related decline of muscle strength for older participants in clinical trials.

  5. Is there a place for combining angiotensin-converting enzyme inhibitors and angiotensin-receptor antagonists in the treatment of hypertension, renal disease or congestive heart failure?

    Science.gov (United States)

    Taylor, A A

    2001-09-01

    Angiotensin-converting enzyme inhibitors and angiotensin II receptor subtype 1 antagonists have proven to be effective and well tolerated antihypertensive agents. They also exhibit unique cardioprotective and renoprotective properties in patients with comorbid conditions such as congestive heart failure and proteinuria or renal insufficiency. This benefit is observed most dramatically in diabetic persons. Although inconclusive, the results of a limited number of clinical trials support the notion that additive antihypertensive, cardioprotective, and renoprotective effects may be obtained with combined used of angiotensin-converting enzyme inhibitors and angiotensin II receptor subtype 1 antagonists in some patients. More studies are needed to confirm the findings of these preliminary studies, and to define more clearly those subsets of patients who might derive the greatest benefit from angiotensin-converting enzyme inhibitor-angiotensin II receptor subtype 1 antagonist combination therapy.

  6. Angiotensin I-converting enzyme inhibitor peptides derived from the endostatin-containing NC1 fragment of human collagen XVIII.

    Science.gov (United States)

    Farias, Shirley L; Sabatini, Regiane A; Sampaio, Tatiana C; Hirata, Izaura Y; Cezari, Maria Helena S; Juliano, Maria A; Sturrock, Edward D; Carmona, Adriana K; Juliano, Luiz

    2006-05-01

    Extracellular matrix and soluble plasma proteins generate peptides that regulate biological activities such as cell growth, differentiation and migration. Bradykinin, a peptide released from kininogen by kallikreins, stimulates vasodilatation and endothelial cell proliferation. Various classes of substances can potentiate these biological actions of bradykinin. Among them, the best studied are bradykinin potentiating peptides (BPPs) derived from snake venom, which can also strongly inhibit angiotensin I-converting enzyme (ACE) activity. We identified and synthesized sequences resembling BPPs in the vicinity of potential proteolytic cleavage sites in the collagen XVIII molecule, close to endostatin. These peptides were screened as inhibitors of human recombinant wild-type ACE containing two intact functional domains; two full-length ACE mutants containing only a functional C- or N-domain catalytic site; and human testicular ACE, a natural form of the enzyme that only contains the C-domain. The BPP-like peptides inhibited ACE in the micromolar range and interacted preferentially with the C-domain. The proteolytic activity involved in the release of BPP-like peptides was studied in human serum and human umbilical-vein endothelial cells. The presence of enzymes able to release these peptides in blood led us to speculate on a physiological mechanism for the control of ACE activities.

  7. The discovery of novel tartrate-based TNF-[alpha] converting enzyme (TACE) inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Rosner, Kristin E.; Guo, Zhuyan; Orth, Peter; Shipps, Jr., Gerald W.; Belanger, David B.; Chan, Tin Yau; Curran, Patrick J.; Dai, Chaoyang; Deng, Yongqi; Girijavallabhan, Vinay M.; Hong, Liwu; Lavey, Brian J.; Lee, Joe F.; Li, Dansu; Liu, Zhidan; Popovici-Muller, Janeta; Ting, Pauline C.; Vaccaro, Henry; Wang, Li; Wang, Tong; Yu, W.; Zhou, G.; Niu, X.; Sun, J.; Kozlowski, J.A.; Lundell, D.J.; Madison, V.; McKittrick, B.; Piwinski, J.J.; Shih, N.Y.; Siddiqui, M. Arshad; Strickland, Corey O. (SPRI)

    2010-09-17

    A novel series of TNF-{alpha} convertase (TACE) inhibitors which are non-hydroxamate have been discovered. These compounds are bis-amides of L-tartaric acid (tartrate) and coordinate to the active site zinc in a tridentate manner. They are selective for TACE over other MMP's. We report the first X-ray crystal structure for a tartrate-based TACE inhibitor.

  8. ANGIOTENSIN CONVERTING ENZYME INHIBITORS IN MANAGEMENT OF PATIENTS WITH CHRONIC HEART FAILURE

    Directory of Open Access Journals (Sweden)

    S. N. Tereshchenko

    2009-01-01

    Full Text Available The role of ACE inhibitors in modern pharmacotherapy of patients with chronic heart failure (CHF is discussed. The actual usage of these highly effective drugs is underlined taking into account high prevalence and social significance of CHF. Necessity of ACE inhibitors usage is confirmed by pharmacodynamic features of these drugs in CHF. The special attention is given to enalapril, that has the biggest evidence base in treatment of CHF patients.

  9. Angiotensin converting enzyme (ACE) inhibitors from Jasminum azoricum and Jasminum grandiflorum.

    Science.gov (United States)

    Somanadhan, B; Smitt, U W; George, V; Pushpangadan, P; Rajasekharan, S; Duus, J O; Nyman, U; Olsen, C E; Jaroszewski, J W

    1998-04-01

    Bioactivity-guided fractionation of extracts of the aerial parts of Jasminum azoricum var. travancorense, using an in vitro ACE inhibition assay, led to isolation of three oligomeric, iridoid-type compounds, which were named sambacein I-III. Their structures are based on spectroscopic and chemical evidence. Similarly, fractionation of extracts of aerial parts of J. grandiflorum resulted in the isolation of the previously reported ACE inhibitor, oleacein. The IC50 values of purified ACE inhibitors were 26-36 microM. Moreover, 2-(3,4-dihydroxyphenyl)-ethanol, isoquercitrin and ursolic acid were isolated from J. grandiflorum. Sambaceins and oleacein are formed from genuine iridoid glucosides during processing of the plant material. NMR spectroscopy was used to measure the level of the ACE inhibitors in the traditional medicines prepared in Kerala from these Jasminum species.

  10. Pioglitazone, a PPARγ agonist, provides comparable protection to angiotensin converting enzyme inhibitor ramipril against adriamycin nephropathy in rat.

    Science.gov (United States)

    Ochodnicky, Peter; Mesarosova, Lucia; Cernecka, Hana; Klimas, Jan; Krenek, Peter; Goris, Maaike; van Dokkum, Richard P E; Henning, Robert H; Kyselovic, Jan

    2014-05-05

    Peroxisome proliferator-activated receptor γ (PPARγ) agonists have been shown to ameliorate diabetic nephropathy, but much less are known about their effects in non-diabetic nephropathies. In the present study, metabolic parameters, blood pressure, aortic endothelial function along with molecular and structural markers of glomerular and tubulointerstitial renal damage, were studied in a rat model of normotensive nephropathy induced by adriamycin and treated with PPARγ agonist pioglitazone (12mg/kg, po), angiotensin converting enzyme (ACE) inhibitor ramipril (1mg/kg, po) or their combination. Pioglitazone had no effect on systolic blood pressure, marginally reduced glycemia and improved aortic endothelium-dependent relaxation. In the kidney, pioglitazone prevented the development of proteinuria and focal glomerulosclerosis to the similar extent as blood-pressure lowering ramipril. Renoprotection provided by either treatment was associated with a reduction in the cortical expression of profibrotic plasminogen activator inhibitor-1 and microvascular damage-inducing endothelin-1, and a limitation of interstitial macrophage influx. Treatment with PPARγ agonist, as well as ACE inhibitor comparably affected renal expression of the renin-angiotensin system (RAS) components, normalizing increased renal expression of ACE and enhancing the expression of Mas receptor. Interestingly, combined pioglitazone and ramipril treatment did not provide any additional renoprotection. These results demonstrate that in a nondiabetic renal disease, such as adriamycin-induced nephropathy, PPARγ agonist pioglitazone provides renoprotection to a similar extent as an ACE inhibitor by interfering with the expression of local RAS components and attenuating related profibrotic and inflammatory mechanisms. The combination of the both agents, however, does not lead to any additional renal benefit.

  11. Fragment-based design for the development of N-domain-selective angiotensin-1-converting enzyme inhibitors.

    Science.gov (United States)

    Douglas, Ross G; Sharma, Rajni K; Masuyer, Geoffrey; Lubbe, Lizelle; Zamora, Ismael; Acharya, K Ravi; Chibale, Kelly; Sturrock, Edward D

    2014-02-01

    ACE (angiotensin-1-converting enzyme) is a zinc metallopeptidase that plays a prominent role in blood pressure regulation and electrolyte homeostasis. ACE consists of two homologous domains that despite similarities of sequence and topology display differences in substrate processing and inhibitor binding. The design of inhibitors that selectively inhibit the N-domain (N-selective) could be useful in treating conditions of tissue injury and fibrosis due to build-up of N-domain-specific substrate Ac-SDKP (N-acetyl-Ser-Asp-Lys-Pro). Using a receptor-based SHOP (scaffold hopping) approach with N-selective inhibitor RXP407, a shortlist of scaffolds that consisted of modified RXP407 backbones with novel chemotypes was generated. These scaffolds were selected on the basis of enhanced predicted interaction energies with N-domain residues that differed from their C-domain counterparts. One scaffold was synthesized and inhibitory binding tested using a fluorogenic ACE assay. A molecule incorporating a tetrazole moiety in the P2 position (compound 33RE) displayed potent inhibition (K(i)=11.21±0.74 nM) and was 927-fold more selective for the N-domain than the C-domain. A crystal structure of compound 33RE in complex with the N-domain revealed its mode of binding through aromatic stacking with His388 and a direct hydrogen bond with the hydroxy group of the N-domain specific Tyr369. This work further elucidates the molecular basis for N-domain-selective inhibition and assists in the design of novel N-selective ACE inhibitors that could be employed in treatment of fibrosis disorders.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    regression analysis demonstrated no differences in risk for all-cause mortality, but patients using captopril had higher risk of reinfarction (hazard ratio 1.18, 95% confidence interval 1.05, 1.34). However, following adjustment for differences in used dosages, all ACE inhibitors had similar clinical...... 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...

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

    DEFF Research Database (Denmark)

    Kamper, A L

    1991-01-01

    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...

  14. Angioedema Related to Angiotensin-Converting Enzyme Inhibitors: Attack Severity, Treatment, and Hospital Admission in a Prospective Multicenter Study.

    Science.gov (United States)

    Javaud, Nicolas; Achamlal, Jallal; Reuter, Paul-George; Lapostolle, Frédéric; Lekouara, Akim; Youssef, Mustapha; Hamza, Lilia; Karami, Ahmed; Adnet, Frédéric; Fain, Olivier

    2015-11-01

    The number of cases of acquired angioedema related to angiotensin converting enzyme inhibitors induced (ACEI-AAE) is on the increase, with a potential concomitant increase in life-threatening attacks of laryngeal edema. Our objective was to determine the main characteristics of ACEI-AAE attacks and, in doing so, the factors associated with likelihood of hospital admission from the emergency department (ED) after a visit for an attack.A prospective, multicenter, observational study (April 2012-December 2014) was conducted in EDs of 4 French hospitals in collaboration with emergency services (SAMU 93) and a reference center for bradykinin-mediated angioedema. For each patient presenting with an attack, emergency physicians collected demographic and clinical presentation data, treatments, and clinical course. They recorded time intervals from symptom onset to ED arrival and to treatment decision, from ED arrival to specific treatment with plasma-derived C1-inhibitor (C1-INH) or icatibant, and from specific treatment to onset of symptom relief. Attacks requiring hospital admission were compared with those not requiring admission.Sixty-two eligible patients with ACEI-AAE (56% men, median age 63 years) were included. Symptom relief occurred significantly earlier in patients receiving specific treatment than in untreated patients (0.5 [0.5-1.0] versus 3.9 [2.5-7.0] hours; P < 0.0001). Even though icatibant was injected more promptly than plasma-derived C1-INH, there, however, was no significant difference in median time to onset of symptom relief between the 2 drugs (0.5 [0.5-1.3] versus 0.5 [0.4-1.0] hours for C1-INH and icatibant, respectively, P = 0.49). Of the 62 patients, 27 (44%) were admitted to hospital from the ED. In multivariate analysis, laryngeal involvement and progressive swelling at ED arrival were independently associated with admission (Odds ratio [95% confidence interval] = 6.2 [1.3-28.2] and 5.9 [1.3-26.5], respectively). A favorable course

  15. The Divergent Cardiovascular Effects of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on Myocardial Infarction and Death.

    Science.gov (United States)

    Strauss, Martin H; Hall, Alistair S

    2016-01-01

    The renin angiotensin aldosterone system (RAAS) plays a central role in the pathophysiology of hypertension and vascular disease. Angiotensin converting enzyme inhibitors (ACEis) suppress angiotensin II (ANG II) concentrations, whereas angiotensin receptor blockers (ARBs) block the binding of ANG II to AT1 receptors. ACEis and ARBs are both effective anti-hypertensive agents and have similar risk reductions in stroke - a blood pressure dependent phenomenon. ACEis also reduce the risk of myocardial infarction (MI) and mortality in high risk hypertensive patients, as well as in diabetics, the elderly, those with vascular disease, and in congestive heart failure. ARBs, in contrast, do not reduce the risk of MI or death in clinical trials where the comparator has been another active therapy or even a placebo. Systematic reviews of ARBs that include meta-analyses or meta-regression analyses confirm that ARBs lack the cardiovascular protective effects of ACEis, which in part are "independent" of blood pressure lowering. Practice guidelines, especially those in high risk hypertensive patients, should reflect the evidence that ACEis and ARBs have divergent cardiovascular effects - ACEis reduce mortality, whereas ARBs do not. ACEis should be the preferred RAAS inhibitor in high risk patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Molecular dynamics simulation and molecular docking studies of Angiotensin converting enzyme with inhibitor lisinopril and amyloid Beta Peptide.

    Science.gov (United States)

    Jalkute, Chidambar Balbhim; Barage, Sagar Hindurao; Dhanavade, Maruti Jayram; Sonawane, Kailas Dasharath

    2013-06-01

    Angiotensin converting enzyme (ACE) cleaves amyloid beta peptide. So far this cleavage mechanism has not been studied in detail at atomic level. Keeping this view in mind, we performed molecular dynamics simulation of crystal structure complex of testis truncated version of ACE (tACE) and its inhibitor lisinopril along with Zn(2+) to understand the dynamic behavior of active site residues of tACE. Root mean square deviation results revealed the stability of tACE throughout simulation. The residues Ala 354, Glu 376, Asp 377, Glu 384, His 513, Tyr 520 and Tyr 523 of tACE stabilized lisinopril by hydrogen bonding interactions. Using this information in subsequent part of study, molecular docking of tACE crystal structure with Aβ-peptide has been made to investigate the interactions of Aβ-peptide with enzyme tACE. The residues Asp 7 and Ser 8 of Aβ-peptide were found in close contact with Glu 384 of tACE along with Zn(2+). This study has demonstrated that the residue Glu 384 of tACE might play key role in the degradation of Aβ-peptide by cleaving peptide bond between Asp 7 and Ser 8 residues. Molecular basis generated by this attempt could provide valuable information towards designing of new therapies to control Aβ concentration in Alzheimer's patient.

  17. Efficacy and Safety of Angiotensin-Converting Enzyme Inhibitors in Patients With Left Ventricular Systolic Dysfunction and Hyponatremia

    DEFF Research Database (Denmark)

    Balling, Louise; Kober, Lars; Schou, Morten;

    2013-01-01

    The presence of hyponatremia has been perceived to increase the risk of adverse events on initiation of treatment with angiotensin-converting enzyme inhibition in heart failure patients. The aim of this study was to investigate if baseline hyponatremia (plasma Na(+)......The presence of hyponatremia has been perceived to increase the risk of adverse events on initiation of treatment with angiotensin-converting enzyme inhibition in heart failure patients. The aim of this study was to investigate if baseline hyponatremia (plasma Na(+)...

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  19. Effects of specific interleukin-1β-converting enzyme inhibitor on ischemic acute renal failure in murine models

    Institute of Scientific and Technical Information of China (English)

    Hua-feng LIU; Dong LIANG; Li-ming WANG; Nan ZHOU; Cui-wei YAO; Tao HONG; De-shen TANG; Xiao-wen CHEN

    2005-01-01

    Aim: To study the effect of selective interleukin-1 β-converting enzyme (ICE,caspase-1) inhibitor on ischemic acute renal failure (ARF). Methods: Mouse models of ischemic ARF were treated with the specific ICE inhibitor AC-YVAD-CMK.A renal function assay and renal morphological studies were employed to estimate the renal protective effect of AC-YVAD-CMK. The survival rate of mouse models was also analyzed by a time series test. Furthermore, renal ICE activity,mature interleukin-18 (IL-18) protein expression and interferon-γ (IFN-γ) mRNA expression were also detected by fluorescent enzyme-linked immunosorbent assay (ELISA), ELISA, and semi-quantitative reverse transcription-polymerase chain reaction, respectively. Results: The levels of blood urea nitrogen (BUN) and serum creatinine (Scr) increased remarkably in the model controls compared with the sham-operated groups (P<0.01). Typical renal tubular necrosis was found in the model controls. Renal ICE activity, mature IL-18 protein expression, and IFN-γmRNA expression were also increased significantly in the model controls compared with the sham-operated groups. The levels of BUN and Scr in the AC-YVAD-CMK therapy group were decreased significantly compared with the untreated model controls (P<0.01). Renal tubulointerstitial lesion was also attenuated significantly (P<0.05). AC-YVAD-CMK therapy alleviated the clinical features of ARF, and increased the survival rate (P<0.01). Furthermore, AC-YVADCMK therapy also decreased ICE activity, mature IL-18 protein expression, and IFN-γ mRNA expression in renal tissue (P<0.05). Conclusion: The selective ICEinhibitor AC-YVAD-CMK can effectively protect the kidney from acute ischemic lesions. This protective effect is associated with decreased renal ICE activity and suppressed IL- 18 maturation and IFN-γ mRNA transcription.

  20. Cardiac mortality in users of olmesartan, other angiotensin-receptor blockers and angiotensin-converting enzyme inhibitors.

    Science.gov (United States)

    Walker, Alexander M; Liang, Caihua; Clifford, C Robin; Parker, Crawford; Feldman, Allen

    2014-04-01

    Clinical trials of olmesartan for prevention of progression of renal disease in patients with diabetes showed renal protection but an unexpected imbalance in cardiac deaths. The US Food and Drug Administration requested from the manufacturer a cohort study of olmesartan, other angiotensin-receptor blockers (ARBs), and angiotensin-converting enzyme (ACE) inhibitors in a large population. A retrospective cohort study was conducted with the cooperation of a US health insurer. Subject entry and follow-up ran from 2002 through 2009. In propensity-matched cohorts, the primary analysis considered continuous current users. Endpoints were sudden cardiac death (SCD) and all-cause mortality, identified through the US National Death Index, supplemented by insurance and hospital discharge data. Statistical estimation was based on proportional hazards analyses with 95% confidence intervals. Power calculations had shown that 25,000 olmesartan initiators would be required to detect relative risks (RRs) of SCD of twofold or greater. A total of 57,123 initiators of olmesartan were matched 1:2 to initiators of other ARBs and 41,801 to initiators of ACE inhibitors. Average follow-up time ranged from 8 to 9 months. Olmesartan initiators and comparators experienced similar patterns of both outcomes, with RRs ≤1.0 and upper confidence bounds ≤1.6. Among persons with prior use of hypoglycemic agents, in comparison with other ARBs, the RR of SCD for olmesartan users was 0.8, with an upper confidence bound of 2.2. The results of this well-powered study do not raise concerns for the risk of SCD or death from all causes among olmesartan users in comparison with users of other ARBs or ACE inhibitors. Copyright © 2013 John Wiley & Sons, Ltd.

  1. Mortality in patients with hypertension on angiotensin-I converting enzyme (ACE)-inhibitor treatment is influenced by the ACE insertion/deletion polymorphism

    NARCIS (Netherlands)

    Bleumink, GS; Schut, Anna F.C.; Sturkenboom, MCJM; van Duijn, CM; Deckers, JW; Hofman, A; Kingma, J. Herre; Witteman, JCM; Stricker, BHC

    2005-01-01

    Background The response to angiotensin-l converting enzyme (ACE)-inhibitor therapy is highly variable. Residual ACE activity during treatment, potentially modified by the ACE insertion/deletion (I/D) polymorphism, may explain part of this variability. We studied the possible interaction between ACE-

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

    DEFF Research Database (Denmark)

    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-Yusu...

  3. ADVANTAGES OF COMBINATION THERAPY OF HYPERTENSION WITH CALCIUM CHANNEL BLOCKER AND ANGIOTENSIN-CONVERTING ENZYME INHIBITOR IN PATIENTS WITH IMPAIRED RENAL FUNCTION

    Directory of Open Access Journals (Sweden)

    N. A. Dzhaiani

    2014-01-01

    Full Text Available Up-to-date data on combination therapy of arterial hypertension in patients with chronic kidney disease are presented. Special attention is paid to the fixed combination of calcium antagonist lercanidipine and angiotensin-converting enzyme inhibitor enalapril.

  4. Polypharmacy in chronic heart failure : practical issues regarding the use of angiotensin-converting enzyme inhibitors, beta-blockers and other drugs

    NARCIS (Netherlands)

    de Boer, RA; van Veldhuisen, DJ

    2002-01-01

    Angiotensin-converting enzyme (ACE) inhibitors and beta-blockers are the cornerstone for treatment of patients with chronic heart failure (CHF), and are usually combined with diuretics, with or without digoxin. With the development of new, additional treatments, the problem of polypharmacy becomes r

  5. Mortality in patients with hypertension on angiotensin-I converting enzyme (ACE)-inhibitor treatment is influenced by the ACE insertion/deletion polymorphism

    NARCIS (Netherlands)

    Bleumink, GS; Schut, Anna F.C.; Sturkenboom, MCJM; van Duijn, CM; Deckers, JW; Hofman, A; Kingma, J. Herre; Witteman, JCM; Stricker, BHC

    Background The response to angiotensin-l converting enzyme (ACE)-inhibitor therapy is highly variable. Residual ACE activity during treatment, potentially modified by the ACE insertion/deletion (I/D) polymorphism, may explain part of this variability. We studied the possible interaction between

  6. 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

    NARCIS (Netherlands)

    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

  7. Polypharmacy in chronic heart failure : practical issues regarding the use of angiotensin-converting enzyme inhibitors, beta-blockers and other drugs

    NARCIS (Netherlands)

    de Boer, RA; van Veldhuisen, DJ

    Angiotensin-converting enzyme (ACE) inhibitors and beta-blockers are the cornerstone for treatment of patients with chronic heart failure (CHF), and are usually combined with diuretics, with or without digoxin. With the development of new, additional treatments, the problem of polypharmacy becomes

  8. IC 50-to-K i: a web-based tool for converting IC 50 to K i values for inhibitors of enzyme activity and ligand binding

    OpenAIRE

    Cer, R. Z.; Mudunuri, U.; Stephens, R.; Lebeda, F. J.

    2009-01-01

    A new web-server tool estimates K i values from experimentally determined IC 50 values for inhibitors of enzymes and of binding reactions between macromolecules (e.g. proteins, polynucleic acids) and ligands. This converter was developed to enable end users to help gauge the quality of the underlying assumptions used in these calculations which depend on the type of mechanism of inhibitor action and the concentrations of the interacting molecular species. Additional calculations are performed...

  9. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in high vascular risk.

    Science.gov (United States)

    Potier, Louis; Roussel, Ronan; Elbez, Yedid; Marre, Michel; Zeymer, Uwe; Reid, Christopher M; Ohman, Magnus; Eagle, Kim A; Bhatt, Deepak L; Steg, Philippe Gabriel

    2017-09-01

    ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are widely prescribed in patients with high cardiovascular (CV) risk. However, whether both classes have equivalent effectiveness to prevent CV events remains unclear. The aim of this study was to compare the incidence of major CV events between ACEI and ARB users. The Reduction of Atherothrombosis for Continued Health registry is an observational study who enrolled 69 055 individuals with high CV risk. Among them, 40 625 patients (ACEIs 67.9% and ARBs 32.1%) were included. Main outcome was rates of CV mortality, non-fatal myocardial infarction, non-fatal stroke or hospitalisation for CV disease at 4 years. In a propensity score-adjusted cohort, the incidence of the primary outcome was lower in patients on ARBs compared with ACEIs (29.2% vs 33.4%; adjusted HR 0.90; 95% CI 0.86 to 0.95; pACEIs, especially in patients with established CV disease. Our results suggest that ARBs may provide superior protection against CV events than ACEIs in high-risk patients in real-world practice. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. Angiotensin-converting enzyme inhibitors attenuate propofol-induced pro-oxidative and antifibrinolytic effect in human endothelial cells.

    Science.gov (United States)

    Wojewodzka-Zelezniakowicz, Marzena; Gromotowicz-Poplawska, Anna; Kisiel, Wioleta; Konarzewska, Emilia; Szemraj, Janusz; Ladny, Jerzy Robert; Chabielska, Ewa

    2017-01-01

    The aim of this study was to investigate the effects of plasma and tissue angiotensin-converting enzyme inhibitors (ACE-Is) against propofol-induced endothelial dysfunction and to elucidate the involved mechanisms in vitro. We examined the effects of propofol (50 μM), quinaprilat and enalaprilat (10(-5) M) on fibrinolysis (t-PA, PAI-1, TAFI antigen levels), oxidative stress parameters (H2O2 and MDA antigen levels and SOD and NADPH oxidase mRNA levels) and nitric oxide bioavailability (NO2/NO3 concentration and NOS expression at the level of mRNA) in human umbilical vein endothelial cells (HUVECs). We found that both ACE-Is promoted similar endothelial fibrinolytic properties and decreased oxidative stress in vitro. Propofol alone increased the release of antifibrinolytic and pro-oxidative factors from the endothelium and increased mRNA iNOS expression. We also found that the incubation of HUVECs in the presence of propofol following ACE-Is pre-incubation caused weakness of the antifibrinolytic and pro-oxidative potential of propofol and this effect was similar after both ACE-Is. This observation suggests that the studied ACE-Is exerted protective effects against endothelial cell dysfunction caused by propofol, independently of hemodynamics.

  11. Angiotensin-converting enzyme inhibitor-induced angioedema and hereditary angioedema: a comparison study of attack severity.

    Science.gov (United States)

    Javaud, Nicolas; Charpentier, Stéphane; Lapostolle, Frédéric; Lekouara, Hakim; Boubaya, Marouane; Lenoir, Gilles; Mekinian, Arsène; Adnet, Frédéric; Fain, Olivier

    2015-01-01

    Objective There appears to be differences in the clinical presentation of hereditary angioedema (HAE) and angiotensin-converting enzyme inhibitor-induced (ACE-I) angioedema (AE). The aim of this study was to compare the clinical characteristics of these two AE forms. Methods We conducted a retrospective study of consecutive patients with HAE or ACE-I AE. The attack characteristics experienced by the patients were compared by a logistic regression analysis using generalized estimating equations. Results A total of 56 patients were included in this study (ACE-I AE, n=25; HAE, n=31). A total of 534 attacks were documented. Severe attacks were more common in the patients who had an acute episode of ACE-I AE than HAE. Swelling of the tongue, lips and larynx were significantly associated with ACE-I AE [OR: 8.70 (95% CI, 1.04-73.70), OR: 20.4 (95% CI, 4.9-84.2) and OR: 7.50 (95% CI, 1.20-48.30), respectively]. Conclusion Swelling of the tongue, lips and larynx are significantly more frequent in drug-induced AE than HAE.

  12. Angiotensin-converting enzyme inhibitor captopril prevents activation-induced apoptosis by interfering with T cell activation signals

    Science.gov (United States)

    Odaka, C; Mizuochi, T

    2000-01-01

    Captopril is an orally active inhibitor of angiotensin-converting enzyme (ACE) which is widely used as an anti-hypertensive agent. In addition to its ability to reduce blood pressure, captopril has a number of other biological activities. Recently the drug was shown to inhibit Fas-induced apoptosis in human activated peripheral T cells and human lung epithelial cells. In this study, we investigated whether captopril blocks activation-induced apoptosis in murine T cell hybridomas, and found that captopril inhibited IL-2 synthesis and apoptotic cell death upon activation with anti-CD3 antibody. In addition, captopril inhibited an inducible caspase-3-like activity during activation-induced apoptosis. On the other hand, captopril did not interfere with Fas signalling, since anti-Fas antibody-induced apoptosis in Fas+ Jurkat cells was unaffected by the drug. Furthermore, we examined whether captopril blocks activation-induced apoptosis by interfering with expression of Fas, Fas ligand (FasL), or both on T cell hybridomas. FasL expression on activated T cells was significantly inhibited by captopril, whereas up-expression of Fas was partially inhibited, as assessed by cell surface staining. Taking all data together, we conclude that captopril prevents activation-induced apoptosis in T cell hybridomas by interfering with T cell activation signals. Captopril has been reported to induce systemic lupus erythematosus syndrome, and our findings may be useful for elucidating the mechanism of captopril-induced autoimmunity. PMID:10971519

  13. Effects of Spironolactone in Combination with Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers in Patients with Proteinuria

    Directory of Open Access Journals (Sweden)

    Ha Yeon Kim

    2014-12-01

    Full Text Available Background/Aims: This study aimed to investigate the potential beneficial anti-proteinuric effect of an add-on aldosterone blockade and the impact of the aldosterone escape phenomenon. Methods: We retrospectively analyzed data of 304 patients with persistent proteinuria, who were administered spironolactone (25 mg/day after treatment with angiotensin-converting enzyme inhibitors (ACEIs or angiotensin II receptor blockers (ARBs for >3 months. Patients were divided according to their aldosterone levels during ACEI/ARB treatment into an escape group (plasma aldosterone >80 pg/mL, N=95, 31.5% and a non-escape group (plasma aldosterone ≤80 pg/mL, N=209, 68.5% and according to their urine albumin-to-creatinine ratio (UACR and estimated glomerular filtration rate (eGFR. Results: After 12 months, the UACR decreased significantly in patients with 1≤UACR2, and in the non-escape group. Severe hyperkalemia (K≥7.0 mEq/L developed in 9 of 137 patients with eGFR2 (6.5% and in none of the 167 patients with eGFR≥60 mL/min/1.73 m2. Conclusions: Proteinuria decreased significantly after add-on spironolactone treatment in patients with 1≤UACR2, and in the non-escape group. The anti-proteinuric effect of spironolactone may vary according to the degree of albuminuria, impaired eGFR, and aldosterone escape.

  14. Hyperkalemia of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in hemodialysis: a meta-analysis.

    Science.gov (United States)

    Zhang, Qian; Luan, Hong; Wang, Le; Zhang, Miao; Chen, Yan; Lv, Yongman; Ma, Zufu

    2012-10-01

    The safety of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) used in hemodialysis (HD) patients was evaluated. Medline, Embase, the Cochrane Library, some databases of clinical trial registries, grey literatures, other reference lists of eligible articles and review articles for the randomized clinical trials (RCTs) on comparison of ACEIs/ARBs or placebo in HD patients were retrieved. RCTs reporting the risk of hyperkalemia by using ACEIs/ARBs in HD patients were selected. Eight articles met the eligibility criteria and were subjected to meta-analysis by using the Cochrane Collaboration's RevMan 4.2 software package. The results showed that there was no significant difference in hyperkalemia in HD patients between ACEIs or ARBs group and control group (ACEIs vs. control: RD=0.03, 95% CI=-0.13-0.18, Z=0.34, P=0.73; ARBs vs. control: RD=-0.02, 95% CI=-0.07-0.03, Z=0.75, P=0.45). However, there was no significant difference in the serum potassium between ACEIs or ARBs group and control group in HD patients (ACEIs vs. control: WMD=0.10, 95% CI=0.06-0.15, Z=4.64, PACEIs or ARBs could not cause an increased risk of hyperkalemia in HD patients, however the serum potassium could be increased with use of ACEIs in HD patients. Therefore the serum potassium concentration should still be closely monitored when ACEIs are taken during the maintenance HD.

  15. Renoprotective Effect of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Diabetic Patients with Proteinuria

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    Feng-Yi Hsu

    2017-06-01

    Full Text Available Background/Aims: Limited evidence exists on the choice of angiotensin-converting enzyme inhibitors (ACEIs and angiotensin II receptor blockers (ARBs in diabetic patients with nephropathy. We aim to assess the renal effectiveness and safety of these drugs among diabetic nephropathy patients. Methods: This retrospective cohort study was conducted with diabetic nephropathy patients who initiated ACEI or ARB monotherapy. The primary outcome was a composite of end stage of renal disease and renal transplantation, and the secondary outcome was all-cause mortality. The safety endpoint was hyperkalemia. Results: Three thousand seven hundred and thirty-nine ACEI users and 3,316 ARB users were identified. ARBs seemed to be inferior to ACEIs given their poorer renal outcome (HR 1.31; 95% CI, 1.15-1.50 and higher risk of hyperkalemia (HR 1.17; 95% CI, 1.04-1.32. Among the four ACEIs compared, captopril was an inferior treatment choice given its poorer renal outcomes (HR 1.42; 95% CI, 1.05-1.93 and higher mortality rate (HR 1.25; 95% CI, 1.01-1.55. Irbesartan appeared to be a poorer treatment choice among the three ARBs compared, given its inferior renal protective effect (HR 1.35; 95% CI, 1.03-1.78. Conclusions: Our findings suggest ACEIs as a relatively more renoprotective and safer treatment as compared to ARBs. Captopril and irbesartan may be inferior to the other ACEIs and ARBs respectively.

  16. Transdermal delivery of angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs) and others for management of hypertension.

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    Ahad, Abdul; Al-Mohizea, Abdullah Mohammed; Al-Jenoobi, Fahad Ibrahim; Aqil, Mohd

    2016-01-01

    Angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs) are some of the most commonly prescribed medications for hypertension. Most of all conventional dosage forms of ARBs and ACEIs undergo extensive first-pass metabolism, which significantly reduces bioavailability. Majority of ARBs and ACEIs are inherently short acting due to a rapid elimination half-life. In addition, oral dosage forms of ARBs and ACEIs have many high incidences of adverse effects due to variable absorption profiles, higher frequency of administration and poor patient compliance. Many attempts have been made globally at the laboratory level to investigate the skin permeation and to develop transdermal therapeutic systems of various ARBs, ACEIs and other anti-hypertensives, to circumvent the drawbacks associated with their conventional dosage form. This manuscript presents an outline of the transdermal research specifically in the area of ARBs, ACEIs and other anti-hypertensives reported in various pharmaceutical journals. The transdermal delivery has gained a significant importance for systemic treatment as it is able to avoid first-pass metabolism and major fluctuations of plasma levels typical of repeated oral administration. As we can experience from this review article that transdermal delivery of different ARBs and ACEIs improves bioavailability as well as patient compliance by many folds. In fact, the rationale development of some newer ARBs, ACEIs and other anti-hypertensives transdermal systems will provide new ways of treatment, circumventing current limitations for conventional dosage forms.

  17. Adverse drug reaction monitoring with angiotensin converting enzyme inhibitors: A prospective, randomized, open-label, comparative study.

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    Sangole, Nishant V; Dadkar, Vaishali N

    2010-02-01

    Angiotensin converting enzyme inhibitors (ACEIs) are known to possess different chemical structures, and change in structure of a drug can bring about change in its adverse drug reaction (ADR) profile. The study aims to observe the incidence and severity of ADRs between the di-carboxyl group containing ACEIs (d-ACEIs) versus phosphonate group containing ACEIs (p-ACEIs), in patients suffering from essential hypertension. One hundred and twenty patients with essential hypertension were randomized into four groups receiving enalapril, lisinopril, ramipril, and fosinopril. They were followed up for four months, to observe the clinical efficacy along with the associated ADRs. Mild, dry brassy cough (% incidence; 95% CI) was observed with d-ACEIs (6.6%; 0 to 15.6) versus p-ACEI (20%; 5.7 to 34.3), in which the cough observed was moderate-to-severe in intensity and two patients required treatment discontinuation (P ACEIs, whereas, two patients on p-ACEI (6.6%; 0 to15.6) had hypotension (P ACEIs had nausea, which was not observed with p-ACEI treatment (0%) (P ACEIs may have a probable relationship with increase in the incidence and severity of ADRs such as dry brassy cough and hypotension. The di-carboxyl group in d-ACEIs may have a probable relationship with increase in the incidence of ADRs like nausea.

  18. Renoprotective Effect of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Diabetic Patients with Proteinuria.

    Science.gov (United States)

    Hsu, Feng-Yi; Lin, Fang-Ju; Ou, Huang-Tz; Huang, Shih-Hui; Wang, Chi-Chuan

    2017-01-01

    Limited evidence exists on the choice of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in diabetic patients with nephropathy. We aim to assess the renal effectiveness and safety of these drugs among diabetic nephropathy patients. This retrospective cohort study was conducted with diabetic nephropathy patients who initiated ACEI or ARB monotherapy. The primary outcome was a composite of end stage of renal disease and renal transplantation, and the secondary outcome was all-cause mortality. The safety endpoint was hyperkalemia. Three thousand seven hundred and thirty-nine ACEI users and 3,316 ARB users were identified. ARBs seemed to be inferior to ACEIs given their poorer renal outcome (HR 1.31; 95% CI, 1.15-1.50) and higher risk of hyperkalemia (HR 1.17; 95% CI, 1.04-1.32). Among the four ACEIs compared, captopril was an inferior treatment choice given its poorer renal outcomes (HR 1.42; 95% CI, 1.05-1.93) and higher mortality rate (HR 1.25; 95% CI, 1.01-1.55). Irbesartan appeared to be a poorer treatment choice among the three ARBs compared, given its inferior renal protective effect (HR 1.35; 95% CI, 1.03-1.78). Our findings suggest ACEIs as a relatively more renoprotective and safer treatment as compared to ARBs. Captopril and irbesartan may be inferior to the other ACEIs and ARBs respectively. © 2017 The Author(s). Published by S. Karger AG, Basel.

  19. Angiotensin-Converting Enzyme Inhibitor (ACEI-Mediated Amelioration in Renal Fibrosis Involves Suppression of Mast Cell Degranulation

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    Nan Sun

    2016-02-01

    Full Text Available Background/Aims: The mechanism by which angiotensin-converting enzyme inhibitors (ACEIs attenuate renal fibrosis has not been fully uncovered. Methods: Renal fibrosis in rats was triggered by unilateral ureteral obstruction (UUO and treated with Enalapril. Results: Enalapril attenuated renal fibrosis, as evidenced by the fibrosis scores (1.07±0.73 versus 2.18±0.75 for 200 mg/ml Enalapril versus control, pwsh/wsh mice developing renal fibrosis. We detected lower levels of transforming growth factor β (TGF-β and alpha-smooth muscle actin (α-SMA, a fibroblast activation marker in the kidney tissue of Enalapril-treated UUO rats relative to the control UUO rats. Enalapril-treated UUO rats exhibited far fewer mast cells infiltrating per area in the kidney tissue than the control UUO rats (8.00±0.65 versus 29.00±0.57, pin vivo. Conclusion: Enalapril attenuated renal fibrosis in UUO rats, possibly by a mechanism involving the suppression of mast cell degranulation.

  20. Angiotensin-converting enzyme inhibitors attenuate propofol-induced pro-oxidative and antifibrinolytic effect in human endothelial cells

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    Marzena Wojewodzka-Zelezniakowicz

    2017-01-01

    Full Text Available Introduction: The aim of this study was to investigate the effects of plasma and tissue angiotensin-converting enzyme inhibitors (ACE-Is against propofol-induced endothelial dysfunction and to elucidate the involved mechanisms in vitro. Materials and methods: We examined the effects of propofol (50 μM, quinaprilat and enalaprilat (10−5 M on fibrinolysis (t-PA, PAI-1, TAFI antigen levels, oxidative stress parameters (H2O2 and MDA antigen levels and SOD and NADPH oxidase mRNA levels and nitric oxide bioavailability (NO2/NO3 concentration and NOS expression at the level of mRNA in human umbilical vein endothelial cells (HUVECs. Results: We found that both ACE-Is promoted similar endothelial fibrinolytic properties and decreased oxidative stress in vitro. Propofol alone increased the release of antifibrinolytic and pro-oxidative factors from the endothelium and increased mRNA iNOS expression. We also found that the incubation of HUVECs in the presence of propofol following ACE-Is pre-incubation caused weakness of the antifibrinolytic and pro-oxidative potential of propofol and this effect was similar after both ACE-Is. Conclusions: This observation suggests that the studied ACE-Is exerted protective effects against endothelial cell dysfunction caused by propofol, independently of hemodynamics.

  1. Pharmacological and clinical studies with temocapril, an angiotensin converting enzyme inhibitor that is excreted in the bile.

    Science.gov (United States)

    Yasunari, Kenichi; Maeda, Kensaku; Nakamura, Munehiro; Watanabe, Takanori; Yoshikawa, Junichi; Asada, Akira

    2004-01-01

    Temocapril is an angiotensin converting enzyme inhibitor (ACEI), a prodrug with a thiazepine ring. Its active form, temocaprilat, is slightly more potent than enalaprilat in inhibiting ACE isolated from rabbit lung. The inhibitory potency of temocaprilat on isolated rat aorta is 3 times that of enalaprilat. Temocapril is excreted in the bile and urine and can be used in patients with renal insufficiency. It reduces blood pressure without causing any significant change in heart rate or cardiac output. Temocapril has been reported to improve endothelial dysfunction in vitro by suppressing increased oxidative stress. In vivo it improves reactive hyperemia in patients with essential hypertension. It has been reported to prevent coronary vascular remodeling in vivo by suppressing local ACE and increased oxidative stress. In humans temocapril has been found to improve insulin resistance partly by increasing adiponectin levels. Cardiac remodeling was improved by temocapril not only in experiment animals but also in humans. It improves renal function and decreases urinary albumin excretion in diabetics as well as in hypertensive patients. Temocapril is currently marketed only in Japan. Considering its beneficial effects and unique pharmacokinetics, temocapril, is likely to be introduced in other countries as well.

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

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    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.

  3. IC50-to-Ki: a web-based tool for converting IC50 to Ki values for inhibitors of enzyme activity and ligand binding.

    Science.gov (United States)

    Cer, R Z; Mudunuri, U; Stephens, R; Lebeda, F J

    2009-07-01

    A new web-server tool estimates K(i) values from experimentally determined IC(50) values for inhibitors of enzymes and of binding reactions between macromolecules (e.g. proteins, polynucleic acids) and ligands. This converter was developed to enable end users to help gauge the quality of the underlying assumptions used in these calculations which depend on the type of mechanism of inhibitor action and the concentrations of the interacting molecular species. Additional calculations are performed for nonclassical, tightly bound inhibitors of enzyme-substrate or of macromolecule-ligand systems in which free, rather than total concentrations of the reacting species are required. Required user-defined input values include the total enzyme (or another target molecule) and substrate (or ligand) concentrations, the K(m) of the enzyme-substrate (or the K(d) of the target-ligand) reaction, and the IC(50) value. Assumptions and caveats for these calculations are discussed along with examples taken from the literature. The host database for this converter contains kinetic constants and other data for inhibitors of the proteolytic clostridial neurotoxins (http://botdb.abcc.ncifcrf.gov/toxin/kiConverter.jsp).

  4. Pharmacogenetic Risk Stratification in Angiotensin-Converting Enzyme Inhibitor-Treated Patients with Congestive Heart Failure: A Retrospective Cohort Study.

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    Karl Emil Nelveg-Kristensen

    Full Text Available 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 SNPs of the angiotensin-converting enzyme gene (rs4343 and ABO blood group genes (rs495828 and rs8176746.Danish patients with CHF enrolled in the previously reported Echocardiography and Heart Outcome Study were included. Subjects were genotyped and categorized according to pharmacogenetic scores A and B of ≤1, 2 and ≥3 each, and followed for up to 10 years. Difference in cumulative incidences of cardiovascular death and all-cause death were assessed by the cumulative incidence estimator. Survival was modeled by Cox proportional hazard analyses.We included 667 patients, of whom 80% were treated with ACEIs. Differences in cumulative incidences of cardiovascular death (P = 0.346 and P = 0.486 and all-cause death (P = 0.515 and P = 0.486 were not significant for score A and B, respectively. There was no difference in risk of cardiovascular death or all-cause death between subjects with score A ≤1 vs. 2 (HR 1.03 [95% CI 0.79-1.34] and HR 1.11 [95% CI 0.88-1.42], score A ≤1 vs. ≥3 (HR 0.80 [95% CI 0.59-1.08] and HR 0.91 [95% CI 0.70-1.20], score B ≤1 vs. 2 (HR 1.02 [95% CI 0.78-1.32] and HR 0.98 [95% CI 0.77-1.24], and score B ≤1 vs. ≥3 (HR 1.03 [95% CI 0.75-1.41] and HR 1.05 [95% CI 0.79-1.40], respectively.We found no association between either of the analyzed pharmacogenetic scores and fatal outcomes in ACEI-treated patients with CHF.

  5. Pharmacogenetic Risk Stratification in Angiotensin-Converting Enzyme Inhibitor-Treated Patients with Congestive Heart Failure: A Retrospective Cohort Study

    Science.gov (United States)

    Nelveg-Kristensen, Karl Emil; Busk Madsen, Majbritt; Torp-Pedersen, Christian; Køber, Lars; Egfjord, Martin; Berg Rasmussen, Henrik; Riis Hansen, Peter

    2015-01-01

    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 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 scores A and B of ≤1, 2 and ≥3 each, and followed for up to 10 years. Difference in cumulative incidences of cardiovascular death and all-cause death were assessed by the cumulative incidence estimator. Survival was modeled by Cox proportional hazard analyses. Results We included 667 patients, of whom 80% were treated with ACEIs. Differences in cumulative incidences of cardiovascular death (P = 0.346 and P = 0.486) and all-cause death (P = 0.515 and P = 0.486) were not significant for score A and B, respectively. There was no difference in risk of cardiovascular death or all-cause death between subjects with score A ≤1 vs. 2 (HR 1.03 [95% CI 0.79–1.34] and HR 1.11 [95% CI 0.88–1.42]), score A ≤1 vs. ≥3 (HR 0.80 [95% CI 0.59–1.08] and HR 0.91 [95% CI 0.70–1.20]), score B ≤1 vs. 2 (HR 1.02 [95% CI 0.78–1.32] and HR 0.98 [95% CI 0.77–1.24]), and score B ≤1 vs. ≥3 (HR 1.03 [95% CI 0.75–1.41] and HR 1.05 [95% CI 0.79–1.40]), respectively. Conclusions We found no association between either of the analyzed pharmacogenetic scores and fatal outcomes in ACEI

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

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    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.

  7. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers reduced dementia risk in patients with diabetes mellitus and hypertension.

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    Kuan, Yi-Chun; Huang, Kuang-Wei; Yen, Der-Jen; Hu, Chaur-Jong; Lin, Cheng-Li; Kao, Chia-Hung

    2016-10-01

    The effects of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) on dementia risk in patients with type 2 diabetes mellitus (DM) and hypertension remain unknown. We investigated the effects of ACEIs and ARBs on dementia risk in patients with type 2 DM and hypertension. We conducted a cohort study by using the Taiwan National Health Insurance Research Database. We included 2377 patients receiving ACEIs and 1780 patients receiving ARBs in the ACEI and ARB cohorts, respectively. We included a comparable number of patients not receiving ACEIs and ARBs as controls in the non-ACEI and non-ARB cohorts through propensity score matching. The effect of ACEIs and ARBs on dementia risk was estimated through multivariate Cox proportional hazard regression after adjustment for several confounding factors. During the 12-year follow-up period, compared with the non-ACEI cohort, all-cause dementia risk decreased by 26% in the ACEI cohort [hazard ratio (HR)=0.74, 95% confidence interval (CI)=0.56-0.96]. The all-cause dementia risk was nearly 40% lower in the ARB cohort than in the non-ARB cohort (HR=0.60, 95% CI=0.37-0.97). These drugs prevented the occurrence of vascular dementia (VD), however, this effect was nonsignificant for Alzheimer's dementia (AD). Treatment duration- and dosage-related protection effects on dementia occurrence were observed. ACEIs and ARBs may effectively prevent all-cause dementia, particularly VD, in patients with type 2 DM and hypertension. Moreover, compared with ACEIs, ARBs appear to be more advantageous in dementia prevention. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Effects of angiotensin-converting enzyme inhibitor, captopril, on bone of mice with streptozotocin-induced type 1 diabetes.

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    Diao, Teng-Yue; Pan, Hai; Gu, Sa-Sa; Chen, Xi; Zhang, Fang-Yi; Wong, Man-Sau; Zhang, Yan

    2014-05-01

    There are contradictory results about the effect of angiotensin-converting enzyme inhibitors (ACEIs) on bone. This study was performed to address the skeletal renin-angiotensin system (RAS) activity and the effects of the ACEI, captopril, on the bone of streptozotocin-induced type 1 diabetic mice. Histochemical assessment on bone paraffin sections was conducted by Safranin O staining and tartrate-resistant acid phosphatase staining. Micro-computed tomography was performed to analyze bone biological parameters. Gene and protein expression were determined by real-time polymerase chain reaction and immunoblotting, respectively. Type 1 diabetic mice displayed osteopenia phenotype and captopril treatment showed no osteoprotective effects in diabetic mice as shown by the reduction of bone mineral density, trabecular thickness and bone volume/total volume. The mRNA expression of ACE and renin receptor, and the protein expression of renin and angiotensin II were markedly up-regulated in the bone of vehicle-treated diabetic mice compared to those of non-diabetic mice, and these molecular changes of skeletal RAS components were effectively inhibited by treatment with captopril. However, treatment with captopril significantly elevated serum tartrate-resistant acid phosphatase 5b levels, reduced the ratio of osteoprotegerin/receptor activator of nuclear factor-κB ligand expression, increased carbonic anhydrase II mRNA expression and the number of matured osteoclasts and decreased transforming growth factor-β and osteocalcin mRNA expression in the tibia compared to those of diabetic mice. The present study demonstrated that the use of the ACEI, captopril, has no beneficial effect on the skeletal biological properties of diabetic mice. However, this could be attributed, at least partially, to its suppression of osteogenesis and stimulation of osteoclastogenesis, even though it could effectively inhibit high activity of local RAS in the bone of diabetic mice.

  9. Comparative effects of a novel angiotensin-converting enzyme inhibitor versus captopril on plasma angiotensins after myocardial infarction.

    Science.gov (United States)

    Flores-Monroy, Jazmín; Ferrario, Carlos M; Valencia-Hernández, Ignacio; Hernández-Campos, Maria Elena; Martínez-Aguilar, Luisa

    2014-01-01

    The compound 4-tert-butyl-2,6-bis(thiomorpholin-4-ylmethyl)phenol (TBTIF) has molecular characteristics similar to angiotensin-converting enzyme (ACE) inhibitors of the sulfhydryl subclass. To assess its value as a new therapeutic agent, we performed a comparative analysis of the effect of TBTIF versus captopril on the circulating levels of angiotensin (Ang) peptides and bradykinin as well as ACE and ACE2 expression after myocardial infarction. Male Wistar rats were divided into four groups: (1) sham-operated rats; (2) rats subjected to 48 h of coronary artery ligation; (3) rats administered captopril (1 mg/kg, i.m.), and (4) a similar group of rats given TBTIF (1 mg/kg, i.m.). Both drugs were administered 30 min before coronary artery ligation and again 24 h later. Acute myocardial infarction lowered both systolic and left ventricular systolic blood pressures compared to the sham group and increased plasma levels of Ang I, Ang II, Ang(1-7) and Ang(1-12). Administration of either captopril or TBTIF reversed the increases in plasma angiotensins. Interestingly, the levels of plasma Ang(1-7) achieved by administration of TBTIF reached values higher than those recorded with captopril. Both agents reversed the decreases in plasma concentrations of bradykinin; in addition, TBTIF upregulated ACE expression, while both agents suppressed the ACE2 upregulation induced by myocardial infarction. These results demonstrate a beneficial effect of the novel compound TBTIF in suppressing the acute surge in the circulating renin-angiotensin system activity induced by myocardial infarction. The greater effects of this compound in augmenting plasma Ang(1-7) concentrations may be highly significant as drugs which augment the concentration of this heptapeptide will exert cardioprotective actions in part by suppressing the hypertrophic and profibrotic actions of Ang II. © 2014 S. Karger AG, Basel.

  10. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers decrease the incidence of atrial fibrillation: a meta-analysis.

    Science.gov (United States)

    Huang, Gang; Xu, Jun-bo; Liu, Jian-xiong; He, Yong; Nie, Xiao-li; Li, Qiu; Hu, Yong-mei; Zhao, Si-qin; Wang, Mian; Zhang, Wen-yong; Liu, Xiao-rong; Wu, Tao; Arkin, Akram; Zhang, Ting-jie

    2011-07-01

    There is not a general agreement regarding antiarrhythmic effects on atrial fibrillation (AF) of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). This study was to assess whether ACEIs and ARBs could decrease the incidence of AF. Medline, Embase and Cochrane Library databases were searched for trials reported from 1950 to May 2009. Search terms included 'randomized controlled trial (RCT), controlled clinical trials, random allocation' and medical subject headings that included all spellings of ACEIs and ARBs agents, 'atrial fibrillation' and 'atrial flutter'. Randomized, controlled human trials of ACEIs or ARBs reporting AF were included. Data were extracted independently by two reviewers using a predefined data extraction sheet, including study quality indicators. Meta-analysis and subgroup analyses were carried out with a random effects model. Twenty-one trials including 91,381 patients and 5730 AF events were identified. Overall, ACEIs/ARBs reduced the relative risk (c) of AF by 25%. In primary and secondary prevention, ACEIs/ARBs decreased the incidence of AF by 24% and 27%, respectively. Patients with hypertension (RR: 0·71, 95%CI: 0·54-0·92), patients with chronic heart failure (RR: 0·58, 95%CI: 0·39-0·87) and those with AF (RR: 0·71, 95%CI: 0·52-0·96) benefited from ACEIs/ARBs treatment. ACEIs/ARBs are effective for primary prevention and secondary prevention of AF. They decrease the incidence of AF especially in patients with hypertension, patients with chronic heart failure and those with AF. © 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.

  11. Impact of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on Mortality of Coronary Artery Bypass Grafting

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    Ahmad Sharafi

    2015-10-01

    Full Text Available Background: There is controversy over the potential benefits/harms of the usage of angiotensin-converting enzyme inhibitors (ACEIs or angiotensin receptor blockers (ARBs as regards the postoperative mortality of coronary artery bypass grafting (CABG. This study investigates the correlation between the in-hospital mortality of CABG and the preoperative administration of ACEI/ARB.Methods: Out of 10055 consecutive patients with isolated CABG from 2006 to 2009, 4664 (46.38% patients received preoperative ACEI/ARB. Data were gathered from the Cardiac Surgery Registry of Tehran Heart Center. In-hospital mortality was defined as death within the same admission for surgery. Adjusted for confounders, multivariable logistic regression models were used to evaluate the impact of preoperative ACEI/ARB therapy on in-hospital death.Results: The mean age of the patients was 60.04 ± 9.51 years and 7364 (73.23% were male. Eighty-seven (0.86% patients expired within 30 days. Multivariate analysis revealed that the administration of ACEI/ARB significantly protected against in-hospital deaths inasmuch as there were 33 (0.70% vs. 54 (1.0% deaths in the ACEI/ARB positive and negative groups, respectively (OR: 0.628; p value = 0.09. Patients without ACEI/ARB were more likely to have a higher global ejection fraction.Conclusion: Preoperative ACEI usage in patients undergoing CABG can be associated with decreased in-hospital mortality. Large-scale randomized clinical trials are suggested.

  12. Preoperative angiotensin-converting enzyme inhibitor use is not associated with increased postoperative pain and opioid use.

    Science.gov (United States)

    Turan, Alparslan; Atim, Abdulkadir; Dalton, Jarrod E; Keeyapaj, Worasak; Chu, Weihan; Bernstein, Ethan; Fu, Alexander; Jae Ho, Lee; Saager, Leif; Sessler, Daniel I

    2013-12-01

    Angiotensin-converting enzyme inhibitors (ACEIs) increase potent proinflammatory and pain mediators in local tissues. Consistent with these observations, animal and human studies demonstrate that ACEIs have hyperalgesic and proinflammatory properties. However, there is no information in literature whether or not the use of ACEIs is associated with increased postoperative pain. Specifically, we tested the primary hypothesis that use of ACEIs is independently associated with increased opioid requirements and pain scores during the initial 72 hours after surgery. Data from 9993 patients undergoing colorectal resection, hysterectomy, nephrectomy, or open prostatectomy were obtained from the Cleveland Clinic Perioperative Health Documentation System. A propensity-matching procedure was used to pair ACEI users to similar nonusers. Corresponding estimates and Bonferroni-adjusted 95% confidence intervals for the effect of ACEIs on each outcome were also estimated. The exact matching procedure, based on type of surgery and propensity score, identified 1038 matched pairs. The final analyzed subsample size was 212. The adjusted difference in mean 72-hour postoperative using a time-weighted average pain score was estimated at +0.17 [-0.40, +0.74] units on the verbal response scale. This was not statistically significant (P=0.50). Opioid use was estimated by the percent difference in mean 72-hour total postoperative intravenous morphine equivalent dose at -8.1% [-46%, +56%], which was not statistically significant (P=0.72). In conclusion, after controlling for all available factors, we found no significant difference that postoperative pain-as defined by either pain scores or opioid requirements-differed between patients taking ACEIs and patients not taking ACEIs.

  13. Role of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in the management of atrial fibrillation

    Science.gov (United States)

    Anis, Rafik R

    2009-01-01

    Atrial fibrillation (AF) is the most common clinical arrhythmia, and is difficult to treat. Current treatment strategies are far from optimal. Antiarrhythmic drug therapy to maintain sinus rhythm is limited by inadequate efficacy and potentially serious side effects. New areas of research include targeting the AF substrate and examining whether drugs can produce atrial structural and/or electrophysiological remodelling, and whether this results in a reduction in AF burden. There are two approaches to the treatment of AF. The first approach is cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm. The other approach is the use of rate-controlling drugs allowing AF to persist. In both approaches, the use of anticoagulant drugs is recommended. There is an increasing interest in novel therapeutic approaches that target AF-substrate development. Recent trials suggest that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor II blockers (ARBs) may be useful, particularly in patients with left ventricular hypertrophy, hypertension, chronic heart failure and left ventricular dysfunction. While experimental studies have shown that the pathogenic structural and electrical remodelling of the atria are prevented by inhibition of angiotensin II, the clinical potential and mechanisms of this approach are still under active investigation. The present article will discuss information pertaining to the mechanism of action and clinical use of ACEIs and ARBs in AF. It will also review the current data on the use of ACEIs and ARBs in a high-risk group of AF patients (heart failure, hypertensive with left ventricular hypertrophy, and myocardial infarction), together with the potential benefit of this class type of pharmacological therapy in direct current cardioversion and after radiofrequency catheter ablation. PMID:19492029

  14. Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers therapy and colorectal cancer: a systematic review and meta-analysis.

    Science.gov (United States)

    Dai, Yi-Ning; Wang, Jing-Hua; Zhu, Jin-Zhou; Lin, Jie-Qiong; Yu, Chao-Hui; Li, You-Ming

    2015-09-01

    We aim to investigate the association between angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) therapy and colorectal cancer (CRC) by conducting a systematic review with meta-analysis. Literature was searched on PubMed, Scopus, and the Cochrane library to identify relevant studies evaluating ACEIs/ARBs therapy and risk of CRC incidence or survival of CRC patients. Pooled risk ratio (RR) with 95% confidence intervals was calculated for the association between ACEIs/ARBs and CRC risk and mortality. Eleven observational studies were included in the systematic review. A meta-analysis of six studies totaling 113,048 individuals indicated a 6% decreased risk of CRC in ACEIs/ARBs users compared to non-users (95% CI 0.89-0.98). In the four case-control studies, individuals using ACEIs/ARBs were associated with a 6% decreased risk of CRC (95% CI 0.90-0.99). The meta-analysis of three studies investigating the relationship between ACEIs/ARBs and survival of CRC did not show a significantly decreased mortality in ACEIs/ARBs users (RR 0.81, 95% CI 0.60-1.09). Seven studies evaluated the dose-response relationship between ACEIs/ARBs therapy and CRC, and two of them showed that the association was related to longer duration and higher dose. CEIs/ARBs therapy might be associated with a reduce risk of CRC development, but whether use of these medications improves the outcomes of CRC remains unknown. Large-scale and more robust studies are needed to further explore this association.

  15. Increased Tumor Response to Neoadjuvant Therapy Among Rectal Cancer Patients Taking Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers

    Science.gov (United States)

    Morris, Zachary S.; Saha, Sandeep; Magnuson, William J.; Morris, Brett A.; Borkenhagen, Jenna F.; Ching, Alisa; Hirose, Gayle; McMurry, Vanesa; Francis, David M.; Harari, Paul M.; Chappell, Rick; Tsuji, Stuart; Ritter, Mark A.

    2016-01-01

    BACKGROUND Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly used antihypertensive medications that have been reported to affect aberrant angiogenesis and the dysregulated inflammatory response. Because of such mechanisms, it was hypothesized that these medications might affect the tumor response to neoadjuvant radiation in patients with rectal cancer. METHODS One hundred fifteen patients who were treated with neoadjuvant radiation at the University of Wisconsin (UW) between 1999 and 2012 were identified. Univariate analyses were performed with anonymized patient data. In a second independent data set, 186 patients with rectal cancer who were treated with neoadjuvant radiation at the Queen’s Medical Center of the University of Hawaii (UH) between 1995 and 2010 were identified. These data were independently analyzed as before. Multivariate analyses were performed with aggregate data. RESULTS Among patients taking ACEIs/ARBs in the UW data set, a significant 3-fold increase in the rate of pathologic complete response (pCR) to neoadjuvant therapy (52% vs 17%, P = .001) was observed. This finding was confirmed in the UH data set, in which a significant 2-fold–increased pCR rate (24% vs 12%, P = .03) was observed. Identified patient and treatment characteristics were otherwise balanced between patients taking and not taking ACEIs/ARBs. No significant effect was observed on pCR rates with other medications, including statins, metformin, and aspirin. Multivariate analyses of aggregate data identified ACEI/ARB use as a strong predictor of pCR (odds ratio, 4.02; 95% confidence interval, 2.06–7.82; P ACEIs/ARBs among patients with rectal cancer is associated with a significantly increased rate of pCR after neoadjuvant treatment. PMID:27203227

  16. Angiotensin-converting enzyme inhibitors reduce albuminuria more than angiotensin receptor blockers in patients with type 2 diabetes.

    Science.gov (United States)

    Al-Sayed, Nasreen A; Gao, Tianming; Wells, Brian J; Yu, Changhong; Zimmerman, Robert S

    2013-01-01

    This study retrospectively compared the effects of angiotensin-converting enzyme inhibitors (ACEIs) versus angiotensin receptor blockers (ARBs) as classes with respect to overall mortality and cardiovascular and renal events in patients with type 2 diabetes. An electronic database of medical records was reviewed. A total of 16,489 patients with type 2 diabetes were enrolled and divided into ACEI (n = 12,351) or ARB (n = 4,138) groups. Baseline patient characteristics were compared using univariable analysis. A chi-square test was used for categorical outcomes, and the propensity class was calculated using multivariable logistic regression. Survival analysis was performed to evaluate the effect of ACEIs/ARBs on overall survival, coronary artery disease (CAD), and renal events via Cox regression analysis, adjusting for propensity class and baseline variables. All statistical analyses were conducted using R 2.15.1 software. No significant differences in overall survival (P = .16) and CAD (P = .81) events were observed between groups. With respect to renal events, ARBs increased the risk of creatinine doubling compared with ACEIs, but the difference was not significant (hazard ratio [HR], 1.207; 95% confidence interval [CI], 0.921-1.583; P = .173). Patients who received ARBs had a significantly higher rate of albuminuria than patients who received ACEIs (HR, 1.303; 95% CI, 1.053-1.612; P = .015). The early effects of ACEIs and ARBs on albuminuria outcome seem to be different in type 2 diabetes, favoring the use of ACEIs. A well-designed prospective study is warranted to evaluate this finding.

  17. EVALUATING THE PRESCRIPTION OF ANGIOTENSIN CONVERTING ENZYME INHIBITORS OR RECEPTOR BLOCKERS IN PATIENTS WITH DIABETES IN JORDAN.

    Science.gov (United States)

    Mayyas, Fadia; Bataineh, Wa'ed; Jarab, Anan

    2017-08-17

    The angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are guideline-recommended agents to prevent development and progression of nephropathy and cardiovascular diseases in diabetic Mellitus (DM). The aim of this study was to evaluate the prescription of ACEIs/ARBs in DM patients with guideline indications. electronic data files for diabetes patients were retrospectively reviewed at a primary care setting northern Jordan. Patient's characteristics and data on ACEIs/ARBs were collected. The primary outcome measure was ACEIs/ARBs persistence of prescription in DM patients with guideline indications. 859 DM patients were reviewed. The mean age ± SEM was 60.75±0.41 years. Most of patients (97.4%) had Type 2 DM. 780 patients (90.8%) had at least one clinical indication to use ACEIs/ARBs. Hypertension followed by coronary artery diseases (CAD) and albuminuria were the most common indications for ACEIs/ARBs prescription. 686 (87.9%) of eligible patients were on ACEIs/ARBs. As the number of indications increased, ACEIs/ARBs use has also increased. ACEIs/ARBs were prescribed regularly in about 59% of patients, whereas 40.9% were ex-users. Most of patients received ACEIs/ARBs after the onset of first indication. By multivariate analysis, hypertension, CAD and albuminuria were significant independent predictors of ACEI/ARB prescription. Indications for ACEI/ARBs use are highly prevalent and rate of receipt is relatively high, but with significant lack of persistence of prescription. Management of DM should enforce healthcare professionals'/patients interaction and education to improve medications prescription.

  18. Administration of angiotensin-converting enzyme inhibitors is associated with slow progression of mild aortic stenosis in Japanese patients.

    Science.gov (United States)

    Wakabayashi, Kana; Tsujino, Takeshi; Naito, Yoshiro; Ezumi, Akira; Lee-Kawabata, Masaaki; Nakao, Shinji; Goda, Akiko; Sakata, Yasushi; Yamamoto, Kazuhiro; Daimon, Takashi; Masuyama, Tohru

    2011-05-01

    It is almost unknown which demographic factors or medications affect the progression of aortic stenosis (AS) in Japanese patients with mild AS. We identified a total of 194 patients with native tricuspid valvular AS, defined as a continuous-wave Doppler determined peak aortic valve jet velocity of ≥ 2.0 m/s, in whom echo Doppler studies were repeated at an interim of at least 6 months. Annualized change in peak jet velocity was calculated, and effects of age, sex, diabetes mellitus, blood pressure, serum low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels, and use of statins and antihypertensive agents on the progression of AS were retrospectively evaluated. Peak aortic valve jet velocity was 2.36 ± 0.79 m/s (mean ± SD) and annualized increase in peak aortic valve jet velocity was 0.17 ± 0.32 m/s/year for all the studied patients. The increase in peak aortic valve jet velocity was lower in patients taking angiotensin-converting enzyme inhibitors (ACE-Is) than in those not taking ACE-Is (0.04 ± 0.22 vs. 0.20 ± 0.32 m/s/year, P < 0.05). Such protective associations were not observed for other first-line antihypertensive agents and statins. Multiple linear regression analysis revealed that ACE-I treatment, decrease in left ventricular ejection fraction, and higher peak aortic valve jet velocity at the first echocardiogram were associated with slower progression of AS. Administration of ACE-Is was associated with the slow progression of mild AS in Japanese patients. Prospective study to assess this hypothesis is needed.

  19. Weight loss for reduction of proteinuria in diabetic nephropathy: Comparison with angiotensin-converting enzyme inhibitor therapy

    Directory of Open Access Journals (Sweden)

    M R Patil

    2013-01-01

    Full Text Available Reduction of weight in obese type 2 diabetes mellitus (T2DM individuals is emerging as a significant strategy in the reduction of proteinuria in diabetic nephropathy along with control of hyperglycemia, hypertension, and dyslipidemia. The objective was to evaluate the reduction in 24-h proteinuria in T2DM patients with nephropathy by weight loss, with conventional therapy (angiotensin-converting enzyme [ACE] inhibitors as the control arm. A prospective, randomized controlled trial was conducted between June 2010 and May 2011. T2DM patients with confirmed nephropathy by 24-h urinary protein estimation with a body mass index (BMI of >25 kg/m 2 were studied. Patients who had nondiabetic nephropathy, uncontrolled hypertension (>125/75 mmHg irrespective of antihypertensive drugs, excess weight due to edema or obesity due to other specific diseases, alcoholics, smokers, and patients who were on hemodialysis were excluded from the study. The patients were divided into three groups, namely, group A, patients on ACE inhibitor therapy; group B, patients on lifestyle modifications for weight loss; and group C, patients on an antiobesity drug (orlistat and lifestyle modifications. At the end of 6 months, all the three groups were compared. Data were analyzed using software SPSS version 15.0. This study encompassed a total of 88 patients; 12 patients were dropped during the study period and 76 (group A: 22, group B: 23, and group C: 31 patients remained. The mean age of the patients was 58.36 ± 10.87 years (range: 30-70 years. At baseline, age, gender, mean BMI, waist-to-hip ratio (WHR, and 24-h proteinuria did not vary significantly among the three groups. At 6 months, the mean BMI significantly decreased in group C ( P < 0.001 compared to that in the other two groups. Among the parameters BMI and WHR, the proportional form of BMI correlated well with the degree of reduction in proteinuria (r = 0.397, P = 0.01. Reduction in weight using lifestyle

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

    DEFF Research Database (Denmark)

    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...

  1. Propofol increases vascular relaxation in aging rats chronically treated with the angiotensin-converting enzyme inhibitor captopril.

    Science.gov (United States)

    Gragasin, Ferrante S; Bourque, Stephane L; Davidge, Sandra T

    2013-04-01

    Both propofol use and advanced age are predictors of intraoperative hypotension. We previously demonstrated that propofol enhances vasodilation in mesenteric arteries from aged rats, partly due to increased nitric oxide (NO) bioavailability. Patients chronically treated with angiotensin-converting enzyme (ACE) inhibitors may exhibit refractory hypotension under general anesthesia. We hypothesized that propofol enhances NO-mediated vasodilation in arteries from aged rats chronically treated with ACE inhibitors. Sprague-Dawley rats aged 12 to 13 months were treated with or without captopril for 7 to 8 weeks, yielding a final age of 14 to 15 months at the time of experimentation. Before euthanasia, arterial blood pressures were obtained through carotid artery cannulation. Concentration-response curves to propofol (0.1-100 µM) or methacholine (MCh) (0.01-3 µM) were then assessed on isolated resistance mesenteric arteries (100-200 μm diameter) from both treatment (captopril) and control rats. MCh relaxation was also assessed after propofol pretreatment (1 and 10 µM). N(G)-nitro-l-arginine methyl ester (l-NAME) (100 µM) and meclofenamate (10 µM) were used to inhibit NO and prostaglandin synthesis, respectively. Concentration-response data were summarized as 50% of the maximum relaxation response or area under the curve. Mean arterial blood pressure in the captopril-treated rats was lower than in untreated rats (P = 0.049). When comparing relaxation in arteries from captopril-treated versus untreated rats, concentration-response curves revealed that captopril-treated rats display greater direct propofol relaxation (P = 0.018). MCh relaxation in the absence of propofol, however, was not different between captopril-treated and untreated rats (P = 0.80). Propofol pretreatment increased MCh relaxation in arteries from captopril-treated compared with untreated rats (P = 0.029 for 1 µM and P = 0.020 for 10 µM). Meclofenamate did not have an effect in this response (P

  2. 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?

    DEFF Research Database (Denmark)

    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...

  3. 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?

    DEFF Research Database (Denmark)

    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...

  4. Angiotensin-converting enzyme inhibitors and amyotrophic lateral sclerosis risk: a total population-based case-control study.

    Science.gov (United States)

    Lin, Feng-Cheng; Tsai, Ching-Piao; Kuang-Wu Lee, Johnny; Wu, Ming-Tsang; Tzu-Chi Lee, Charles

    2015-01-01

    Although several studies have shown that use of angiotensin-converting enzyme inhibitors (ACEIs) potentially decreased amyotrophic lateral sclerosis (ALS) risk in animal models, to our knowledge, there has been no human study in the literature discussing this issue. To investigate the association between the use of ACEIs and the risk for developing ALS. This case-control study was conducted using the total population of Taiwanese citizens seen in general medical practice; therefore, the findings can be applied to the general population. The case group comprised 729 patients with newly diagnosed ALS and a severely disabling disease certificate between January 1, 2002, and December 31, 2008. These cases were compared with 14,580 sex-, age-, residence-, and insurance premium-matched control individuals. Use of ACEIs was analyzed using a conditional logistic regression model that controlled for other antihypertensives, aspirin, steroids, nonsteroidal anti-inflammatory drugs, Charlson Comorbidity Index score, length of hospital stay, and number of outpatient visits. The cumulative defined daily dose (cDDD), which indicates the exposed duration of drug use, was estimated as the sum of dispensed DDD of drug and compared with the risk for ALS. All patients with ALS fulfilled El Escorial criteria in this study. Medical claim data past 1 to 5 years of ALS first diagnosis date for patients and claim data from their matched control individuals were included in the analysis. There was a dose-dependent inverse association between ACEI use and the risk for developing ALS. When compared with patients who did not use ACEIs, the adjusted odds ratios were 0.83 (95% CI, 0.65-1.07; P = .15) for the group prescribed ACEIs lower than 449.5 of the cDDD and 0.43 cDDD (95% CI, 0.26-0.72; P = .001) for the group with a cumulative ACEI use of greater than 449.5 cDDD. The association was most predominant in men older than 55 years. Use of ACEIs exhibited a dose-dependent inverse

  5. 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 Collaborative Group

    DEFF Research Database (Denmark)

    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 ...

  6. A unique downstream estrogen responsive unit mediates estrogen induction of proteinase inhibitor-9, a cellular inhibitor of IL-1beta- converting enzyme (caspase 1).

    Science.gov (United States)

    Krieg, S A; Krieg, A J; Shapiro, D J

    2001-11-01

    Recently, proteinase inhibitor 9 (PI-9) was identified as the first endogenous inhibitor of caspase 1 (IL-1beta-converting enzyme). The regulation of PI-9 expression, therefore, has great importance in the control of inflammatory processes. We reported that PI-9 mRNA and protein are rapidly and directly induced by estrogen in human liver cells. Using transient transfections to assay PI-9 promoter truncations and mutations, we demonstrate that this strong estrogen induction is mediated by a unique downstream estrogen responsive unit (ERU) approximately 200 nucleotides downstream of the transcription start site. Using primers flanking the ERU in chromatin immunoprecipitation assays, we demonstrate estrogen-dependent binding of ER to the cellular PI-9 promoter. The ERU consists of an imperfect estrogen response element (ERE) palindrome immediately adjacent to a direct repeat containing two consensus ERE half-sites separated by 13 nucleotides (DR13). In transient transfections, all four of the ERE half-sites in the imperfect ERE and in the DR13 were important for estrogen inducibility. Transfected chicken ovalbumin upstream transcription factor I and II down-regulated estrogen-mediated expression from the ERU. EMSAs using purified recombinant human ERalpha demonstrate high-affinity binding of two ER complexes to the ERU. Further EMSAs showed that one ER dimer binds to an isolated DR13, supporting the view that one ER dimer binds to the imperfect ERE and one ER dimer binds to DR13. Deoxyribonuclease I footprinting showed that purified ER protected all four of the half-sites in the ERU. Our finding that a direct repeat can function with an imperfect ERE palindrome to confer estrogen inducibility on a native gene extends the repertoire of DNA sequences able to function as EREs.

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    pharmacies within 30 d from discharge was obtained from the National Patient Registry and the Danish Registry of Medicinal Product Statistics. RESULTS: Beta-blocker use increased from 38.1% of patients in 1995 to 67.9% in 2002 (OR = 3.85, CI: 3.58-4.13). Women, elderly patients and patients taking loop......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 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...

  8. Screening of inhibitors of angiotensin-converting enzyme (ACE) employing high performance liquid chromatography-electrospray ionization triple quadrupole mass spectrometry (HPLC-ESI-QqQ-MS).

    Science.gov (United States)

    Musharraf, Syed Ghulam; Bhatti, Muhammad Salman; Choudhary, Muhammad Iqbal; Rahman, Atta-Ur

    2017-04-01

    Angiotensin-converting enzyme (ACE) plays a key role in regulating blood pressure in the body by converting the angiotensin I (AI) into angiotensin II (AII). Angiotensin II is a potent vaso-active peptide that causes arterioles to constrict, resulting in increased blood pressure. A rapid and sensitive method for the identification of inhibitors of ACE was developed, and optimized employing HPLC-ESI-QqQ-MS. In this assay, angiotensin I substrate was converted into the product angiotensin II with the catalytic action of ACE. A calibration curve for depleting concentration of angiotensin I was developed and linearity of R(2)=0.999 with a remarkably low concentration of substrate range 20-200nM. The limit of detection and quantification of angiotensin I was found to be 1.93 and 5.84nM, respectively. The enzymatic reaction was optimized for incubation time, concentration, and volume of enzyme and substrate. All reactions were performed at 37°C at pH7.5 with standard incubation time of 20min. Two standard inhibitors, Captopril and Lisinopril, were checked through the newly developed method for their inhibitory potential, and their IC50 values were found to be 3.969 and 0.852μM, respectively. Reproducibility and precision analysis of different experiments showed <9.9% RSD. The developed method can be used for the identification of new ACE inhibitors.

  9. 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

    NARCIS (Netherlands)

    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

  10. Apricot and other seed stones: amygdalin content and the potential to obtain antioxidant, angiotensin I converting enzyme inhibitor and hypocholesterolemic peptides.

    Science.gov (United States)

    García, M C; González-García, E; Vásquez-Villanueva, R; Marina, M L

    2016-11-09

    Stones from olives and Prunus genus fruits are cheap and sustainable sources of proteins and could be potential sources of bioactive peptides. The main limitation to the use of these seeds is the presence of amygdalin. This work proposes to determine amygdalin in olive and Prunus seeds and in protein isolates obtained from them. Moreover, antioxidant, angiotensin I converting enzyme (ACE) inhibitor, and hypocholesterolemic properties will be evaluated in hydrolysates obtained from these seeds. Despite some seeds contained amygdalin, all protein isolates were free of this substance. Two different procedures to obtain bioactive peptides from protein isolates were examined: gastrointestinal digestion and processing with Alcalase, Flavourzyme or Thermolysin. Higher antioxidant, ACE inhibitor and hypocholesterolemic activities were observed when proteins were processed with Alcalase, Flavourzyme or Thermolysin. The highest antioxidant and ACE inhibitor capacities were observed for the Prunus genus seed hydrolysates while the highest capacity to reduce micellar cholesterol solubility was observed for the apricot and olive seed hydrolysates.

  11. 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

    Directory of Open Access Journals (Sweden)

    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.

  12. When Nothing Else Works: Fresh Frozen Plasma in the Treatment of Progressive, Refractory Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema.

    Science.gov (United States)

    Chaaya, Gerard; Afridi, Faraz; Faiz, Arfa; Ashraf, Ali; Ali, Mahrukh; Castiglioni, Analia

    2017-01-11

    Angioedema is a severe form of an allergic reaction characterized by the localized edematous swelling of the dermis and subcutaneous tissues. Angiotensin-converting enzyme inhibitor-induced angioedema (ACEI-IA) is an allergic reaction that can be severe in some cases requiring advanced management measures. Fresh frozen plasma has been used off-labeled in some case reports to improve and to prevent worsening of the angioedema in a few cases of ACEI-IA. We are reporting this case to increase the awareness of physicians and to widen their therapeutic options when encountering this clinically significant condition.

  13. Perioperative angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers for preventing mortality and morbidity in adults.

    Science.gov (United States)

    Zou, Zui; Yuan, Hong B; Yang, Bo; Xu, Fengying; Chen, Xiao Y; Liu, Guan J; Shi, Xue Y

    2016-01-27

    Perioperative hypertension requires careful management. Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs) have shown efficacy in treating hypertension associated with surgery. However, there is lack of consensus about whether they can prevent mortality and morbidity. To systematically assess the benefits and harms of administration of ACEIs or ARBs perioperatively for the prevention of mortality and morbidity in adults (aged 18 years and above) undergoing any type of surgery under general anaesthesia. We searched the current issue of the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 12), Ovid MEDLINE (1966 to 8 December 2014), EMBASE (1980 to 8 December 2014), and references of the retrieved randomized trials, meta-analyses, and systematic reviews. We included randomized controlled trials (RCTs) comparing perioperative administration of ACEIs or ARBs with placebo in adults (aged 18 years and above) undergoing any type of surgery under general anaesthesia. We excluded studies in which participants underwent procedures that required local anaesthesia only, or participants who had already been on ACEIs or ARBs. Two review authors independently performed study selection, assessed the risk of bias, and extracted data. We used standard methodological procedures expected by Cochrane. We included seven RCTs with a total of 571 participants in the review. Two of the seven trials involved 36 participants undergoing non-cardiac vascular surgery (infrarenal aortic surgery), and five involved 535 participants undergoing cardiac surgery, including valvular surgery, coronary artery bypass surgery, and cardiopulmonary bypass surgery. The intervention was started from 11 days to 25 minutes before surgery in six trials and during surgery in one trial. We considered all seven RCTs to carry a high risk of bias. The effects of ACEIs or ARBs on perioperative mortality and acute myocardial infarction were uncertain

  14. Serp2, an Inhibitor of the Interleukin-1β-Converting Enzyme, Is Critical in the Pathobiology of Myxoma Virus

    Science.gov (United States)

    Messud-Petit, Frederique; Gelfi, Jacqueline; Delverdier, Maxence; Amardeilh, Marie-France; Py, Robert; Sutter, Gerd; Bertagnoli, Stephane

    1998-01-01

    Recently, myxoma virus was shown to encode an additional member of the serpin superfamily. The viral gene, called serp2, was cloned, and the Serp2 protein was shown to specifically bind to interleukin-1β (IL-1β)-converting enzyme (ICE), thus inhibiting the cleavage of pro-IL-1β by the protease (F. Petit, S. Bertagnoli, J. Gelfi, F. Fassy, C. Boucraut-Baralon, and A. Milon, J. Virol. 70:5860–5866, 1996). Here, we address the role of Serp2 in the development of myxomatosis, a lethal infectious disease of the European rabbit. A Serp2 mutant myxoma virus was constructed by disruption of the single-copy serp2 gene and insertion of the Escherichia coli gpt gene serving as the selectable marker. A revertant virus was obtained by replacing the E. coli gpt gene by the intact serp2 open reading frame. The Serp2− mutant virus replicated with wild-type kinetics both in rabbit fibroblasts and a rabbit CD4+ T-cell line (RL5). Moderate reduction of cell surface levels of major histocompatibility complex I was observed after infection with wild-type or Serp2− mutant myxoma virus, and both produced white pocks on the chorioallantoic membrane of the chick embryo. After the infection of European rabbits, the Serp2− mutant virus proved to be highly attenuated compared to wild-type myxoma virus, as demonstrated by the clinical course of myxomatosis and the survival rates of infected animals. Pathohistological examinations revealed that infection with wild-type myxoma virus resulted in a blockade of the inflammatory response at the vascular level. In contrast, rapid inflammatory reactions occurred upon infection with the Serp2− mutant virus. Furthermore, lymphocytes in lymph nodes derived from animals inoculated with Serp2 mutant virus were shown to rapidly undergo apoptosis. We postulate that the virulence of myxoma virus in the European rabbit can be partially attributed to an impairment of host inflammatory processes and to the prevention of apoptosis in lymphocytes. The

  15. Patients With Newly Diagnosed Hypertension Treated With the Renin Angiotensin Receptor Blocker Azilsartan Medoxomil vs Angiotensin-Converting Enzyme Inhibitors: The Prospective EARLY Registry.

    Science.gov (United States)

    Schmieder, Roland E; Potthoff, Sebastian A; Bramlage, Peter; Baumgart, Peter; Mahfoud, Felix; Buhck, Hartmut; Ouarrak, Taoufik; Ehmen, Martina; Senges, Jochen; Gitt, Anselm K

    2015-12-01

    For patients with newly diagnosed hypertension, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are usually the first-line therapies. There is, however, no real-life data regarding the relative clinical effectiveness and tolerability of either drug class. The prospective registry, Treatment With Azilsartan Compared to ACE Inhibitors in Antihypertensive Therapy (EARLY), was conducted to evaluate the effectiveness of the ARB azilsartan medoxomil (AZL-M) vs ACE inhibitors in real-world patients. Of the 1153 patients with newly diagnosed hypertension who were included in the registry, 789 were prescribed AZL-M and 364 were prescribed an ACE inhibitor. After multivariate adjustment, AZL-M was found to provide superior blood pressure reduction and better target blood pressure (<140/90 mm Hg) achievement. The proportion of patients with adverse events was not statistically different between groups. The authors conclude that in newly diagnosed hypertensive patients, AZL-M provides superior blood pressure control with a similar safety profile compared with ACE inhibitors.

  16. Updates on the treatment of essential hypertension: a summary of AHRQ's comparative effectiveness review of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and direct renin inhibitors.

    Science.gov (United States)

    Powers, Benjamin; Greene, Laurence; Balfe, Lisa M

    2011-10-01

    In 2007, the Agency for Healthcare Research and Quality (AHRQ) published a comparative effectiveness review (CER) on the benefits and risks of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) for treating essential hypertension in adults. The main findings indicated that the 2 classes of antihypertensive medications caused similar reductions in blood pressure, although higher rates of adverse events, especially cough, were reported by patients treated with ACEIs. In addition, the 2007 review indicated no treatment related differences in lipid levels, glycemic control, or progression of kidney disease among the agents. Since 2007, 39 relevant studies have been published that compare outcomes for adults treated with ACEIs versus ARBs or a drug in one of these 2 classes versus a direct renin inhibitor (DRI). To systematically analyze findings from the new research, AHRQ commissioned and, in June 2011, published an updated comparative effectiveness review on the benefits and risks of agents that target the renin-angiotensin- aldosterone system (RAAS), specifically ACEIs, ARBs, and DRIs. To (a) familiarize health care professionals with the methods and findings from AHRQ's 2011 comparative effectiveness review on ACEIs, ARBs, and DRIs for adults with essential hypertension; (b) provide commentary and encourage consideration of the clinical and managed care applications of the review findings; and (c) identify limitations to the existing research on the benefits and risks of ACEIs, ARBs, and DRIs. Consistent with the findings from AHRQ's 2007 report, the 2011 update indicated no overall differences in blood pressure control, mortality rates, and major cardiovascular events in patients treated with ACEIs versus ARBs. With a low strength of evidence, 2 studies reported a small significantly greater blood pressure reduction for patients treated with the DRI aliskiren versus the ACEI ramipril. Studies evaluating the DRI aliskiren

  17. Synergistic effect of mycophenolate mofetil and angiotensin-converting enzyme inhibitor in patients with chronic allograft nephropathy

    Directory of Open Access Journals (Sweden)

    G.T. Moscoso-Solorzano

    2009-05-01

    Full Text Available Experimental data and few clinical non-randomized studies have shown that inhibition of the renin-angiotensin system by angiotensin-converting enzyme (ACE associated or not with the use of mycophenolate mofetil (MMF could delay or even halt the progression of chronic allograft nephropathy (CAN. In this retrospective historical study, we investigated whether ACE inhibition (ACEI associated or not with the use of MMF has the same effect in humans as in experimental studies and what factors are associated with a clinical response. A total of 160 transplant patients with biopsy-proven CAN were enrolled. Eighty-one of them were on ACE therapy (G1 and 80 on ACEI_free therapy (G2. Patients were further stratified for the use of MMF. G1 patients showed a marked decrease in proteinuria and stabilized serum creatinine with time. Five-year graft survival after CAN diagnosis was more frequent in G1 (86.9 vs 67.7%; P < 0.05. In patients on ACEI-free therapy, the use of MMF was associated with better graft survival. The use of ACEI therapy protected 79% of the patients against graft loss (OR = 0.079, 95%CI = 0.015-0.426; P = 0.003. ACEI and MMF or the use of MMF alone after CAN diagnosis conferred protection against graft loss. This finding is well correlated with experimental studies in which ACEI and MMF interrupt the progression of chronic allograft dysfunction and injury. The use of ACEI alone or in combination with MMF significantly reduced proteinuria and stabilized serum creatinine, consequently improving renal allograft survival.

  18. Calcium channel blockers, angiotensin receptor blockers, and angiotensin-converting enzyme inhibitors: Effectiveness in combination with diuretics or β-blockers for treating hypertension

    Science.gov (United States)

    Bisognano, John D; McLaughlin, Trent; Roberts, Craig S; Tang, Simon SK

    2007-01-01

    This retrospective database analysis compared the effectiveness of dihydropyridine calcium channel blockers (DHPs), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) added to diuretics or β-blockers. Adults with hypertension treated with diuretic or β-blocker monotherapy between 1998 and 2001 were identified from a large US electronic medical records database of primary care practices. Patients were required to have a baseline blood pressure (BP) ≥140/90 mmHg (≥130/80 mmHg for diabetes mellitus) and recorded BP measurements within 6 months before and 1–12 months following index date. Patients were matched 1:1:1 by propensity score to correct for differences in baseline characteristics. 1875 patients met study criteria and 660 (220 in each cohort) were matched based on propensity scores. Matched cohorts had no significant differences in baseline characteristics. Mean changes in systolic/diastolic BP were −17.5/−8.8, −15.7/−6.3, and −13.0/−8.0 mmHg with DHPs, ACE inhibitors, and ARBs, respectively. Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High BP 6/7 goal attainment for each regimen was 47.3%, 40.0%, and 32.2%, respectively. DHPs, ACE inhibitors, and ARBs improved BP when added to patients’ β-blocker or diuretic therapy. The greatest benefits were observed with DHPs, followed by ACE inhibitors, then ARBs. PMID:18078009

  19. The role of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists in the management of diabetic complications.

    Science.gov (United States)

    Podar, Toomas; Tuomilehto, Jaakko

    2002-01-01

    Evidence suggests that ACE inhibitors can be advantageous for prevention and halting progression of both micro- and macrovascular complications in patients with diabetes mellitus. ACE inhibitors are useful antihypertensive agents in both type 1 and type 2 diabetes; however, ACE inhibitor therapy often needs to be supplemented with calcium channel antagonists, beta-blockers or diuretics to achieve good blood pressure control. ACE inhibitors are also indicated in non-hypertensive patients with type 1 and type 2 diabetes who have micro- or macroalbuminuria. The effect of ACE inhibitors in halting the development and progression of retinopathy and, potentially, neuropathy needs further proof in large-scale studies. More recently, angiotensin II receptor antagonists are emerging as drugs with the potential to be successfully included in the management of diabetic complications, especially when ACE inhibitors are not suitable because of adverse effects.

  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

    DEFF Research Database (Denmark)

    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. Calcium channel blockers, angiotensin receptor blockers, and angiotensin-converting enzyme inhibitors: Effectiveness in combination with diuretics or β-blockers for treating hypertension

    Directory of Open Access Journals (Sweden)

    John D Bisognano

    2007-11-01

    Full Text Available John D Bisognano1, Trent McLaughlin2, Craig S Roberts3, Simon SK Tang31Internal Medicine Department, Cardiology Division, the University of Rochester Medical Center, Rochester, NY, USA; 2NDC Health, Phoenix, Arizona, USA; 3Pfizer Inc, New York, NY, USAAbstract: This retrospective database analysis compared the effectiveness of dihydropyridine calcium channel blockers (DHPs, angiotensin-converting enzyme (ACE inhibitors, and angiotensin receptor blockers (ARBs added to diuretics or β-blockers. Adults with hypertension treated with diuretic or β-blocker monotherapy between 1998 and 2001 were identified from a large US electronic medical records database of primary care practices. Patients were required to have a baseline blood pressure (BP ≥140/90 mmHg (≥130/80 mmHg for diabetes mellitus and recorded BP measurements within 6 months before and 1–12 months following index date. Patients were matched 1:1:1 by propensity score to correct for differences in baseline characteristics. 1875 patients met study criteria and 660 (220 in each cohort were matched based on propensity scores. Matched cohorts had no significant differences in baseline characteristics. Mean changes in systolic/diastolic BP were –17.5/–8.8, –15.7/–6.3, and –13.0/–8.0 mmHg with DHPs, ACE inhibitors, and ARBs, respectively. Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High BP 6/7 goal attainment for each regimen was 47.3%, 40.0%, and 32.2%, respectively. DHPs, ACE inhibitors, and ARBs improved BP when added to patients’ β-blocker or diuretic therapy. The greatest benefits were observed with DHPs, followed by ACE inhibitors, then ARBs.Keywords: hypertension, amlodipine besylate, lisinopril, valsartan, Joint National Committee (JNC 6 and 7

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  3. Evaluation of angiotensin-converting enzyme inhibitor's absorption with retention data of micellar thin-layer chromatography and suitable molecular descriptor.

    Science.gov (United States)

    Odovic, Jadranka; Markovic, Bojan; Vladimirov, Sote; Karljikovic-Rajic, Katarina

    2015-01-01

    Twelve angiotensin-converting enzyme (ACE) inhibitors were studied to evaluate correlation between their absorption (ABS) data available in the literature (22-96%) and hydrophobicity parameters (km and Pm/w) obtained in micellar thin-layer chromatography (MTLC) using Brij 35. The theoretical considerations showed that the geometric molecular descriptor-volume value (Vol) should be considered as an independent variable simultaneously with calculated hydrophobicity parameters in multiple linear regression analysis to obtain reliable correlation between ACE inhibitor's absorption and lipophilicity (calculated KOWWINlog P) and that captopril should be excluded from further correlations. The results of MTLC confirmed that between the two hydrophobicity parameters km and Pm/w, for absorption prediction of 11 ACE inhibitors, the micelle-water partition coefficient Pm/w provided higher correlation (R(2) = 0.756), while for the km parameter R(2) = 0.612 was obtained. The micelle-water partition coefficient Pm/w could be considered as analogous to hydrophobicity parameter C0 from reversed-phase thin-layer chromatography. Dissimilar retention behavior of lisinopril indicated its lowest non-polar interaction with micelle, because of its di-acid form. The proposed model which included ACE inhibitors on the opposite site of lipophilicity-lisinopril and fosinopril (KOWWINlog P = -0.96 and KOWWINlog P = 6.61, respectively), both with similar absorption values (25 and 36%, respectively), could indicate that absorption of investigated compounds occurs via two different mechanisms: active and passive transport. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Structure-based rational design of peptide hydroxamic acid inhibitors to target tumor necrosis factor-α converting enzyme as potential therapeutics for hepatitis.

    Science.gov (United States)

    Wu, Dan; Gu, Qiuhong; Zhao, Ning; Xia, Fei; Li, Zhiwei

    2015-12-01

    The human tumor necrosis factor-α converting enzyme (TACE) has recently been raised as a new and promising therapeutic target of hepatitis and other inflammatory diseases. Here, we reported a successful application of the solved crystal structure of TACE complex with a peptide-like ligand INN for rational design of novel peptide hydroxamic acid inhibitors with high potency and selectivity to target and inhibit TACE. First, the intermolecular interactions between TACE catalytic domain and INN were characterized through an integrated bioinformatics approach, with which the key substructures of INN that dominate ligand binding were identified. Subsequently, the INN molecular structure was simplified to a chemical sketch of peptide hydroxamic acid compound, which can be regarded as a linear tripeptide capped by a N-terminal carboxybenzyl group (chemically protective group) and a C-terminal hydroxamate moiety (coordinated to the Zn(2+) at TACE active site). Based on the sketch, a virtual combinatorial library containing 180 peptide hydroxamic acids was generated, from which seven samples were identified as promising candidates by using a knowledge-based protein-peptide affinity predictor and were then tested in vitro with a standard TACE activity assay protocol. Consequently, three designed peptide hydroxamic acids, i.e. Cbz-Pro-Ile-Gln-hydroxamic acid, Cbz-Leu-Ile-Val-hydroxamic acid and Cbz-Phe-Val-Met-hydroxamic acid, exhibited moderate or high inhibitory activity against TACE, with inhibition constants Ki of 36 ± 5, 510 ± 46 and 320 ± 26 nM, respectively. We also examined the structural basis and non-bonded profile of TACE interaction with a designed peptide hydroxamic acid inhibitor, and found that the inhibitor ligand is tightly buried in the active pocket of TACE, forming a number of hydrogen bonds, hydrophobic forces and van der Waals contacts at the interaction interface, conferring both stability and specificity for TACE-inhibitor complex

  5. Cost-effectiveness of angiotensin-converting enzyme inhibitors for the prevention of diabetic nephropathy in The Netherlands--a Markov model.

    Directory of Open Access Journals (Sweden)

    Charles Christian Adarkwah

    Full Text Available OBJECTIVE: Type 2 diabetes is the main cause of end-stage renal disease (ESRD in Europe and the USA. Angiotensin-converting enzyme (ACE inhibitors have a potential to slow down the progression of renal disease and therefore provide a renal-protective effect. The aim of our study was to assess the most cost-effective time to start an ACE inhibitor (or an angiotensin II receptor blocker [ARB] if coughing as a side effect occurs in patients with newly diagnosed type 2 diabetes in The Netherlands. METHODS: A lifetime Markov decision model with simulated 50-year-old patients with newly diagnosed diabetes mellitus was developed using published data on costs and health outcomes and simulating the progression of renal disease. A health insurance perspective was adopted. Three strategies were compared: treating all patients at the time of diagnosing type 2 diabetes, screening for microalbuminuria, and screening for macroalbuminuria. RESULTS: In the base-case analysis, the treat-all strategy is associated with the lowest costs and highest benefit and therefore dominates screening both for macroalbuminuria and microalbuminuria. A multivariate sensitivity analysis shows that the probability of savings is 70%. CONCLUSIONS: In The Netherlands for patients with type 2 diabetes prescription of an ACE inhibitor immediately after diagnosis should be considered if they do not have contraindications. An ARB should be considered for those patients developing a dry cough under ACE inhibitor therapy. The potential for cost savings would be even larger if the prevention of cardiovascular events were considered.

  6. Impact of Angiotensin I-converting Enzyme Inhibitors and Angiotensin II Type-1 Receptor Blockers on Survival of Patients with NSCLC

    Science.gov (United States)

    Miao, Lili; Chen, Wei; Zhou, Ling; Wan, Huanying; Gao, Beili; Feng, Yun

    2016-01-01

    It has been shown that angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) can decrease tumor growth and tumor-associated angiogenesis and inhibit metastasis. Epidermal growth factor receptor (EGFR) mutations are found in approximately 30% of patients with advanced non-small cell lung cancer (NSCLC) in East Asia and in 10–15% of such patients in Western countries. We retrospectively identified 228 patients with histologically confirmed advanced NSCLC and 73 patients with early stage disease; 103 of these patients took antihypertensive drugs, and 112 received treatment with EGFR tyrosine kinase inhibitors (TKIs). There was a significant difference in progression-free survival after first-line therapy (PFS1) between the ACEI/ARB group and the non-ACEI/ARB group. For the patients treated with TKIs, there was a significant difference in PFS but not in overall survival (OS) between the ACEI/ARB group and the non-ACEI/ARB group. For the patients with advanced NSCLC, there was a significant difference in PFS1 between the ACEI/ARB group and the non-ACEI/ARB group. ACEI/ARB in combination with standard chemotherapy or TKIs had a positive effect on PFS1 or OS, regardless of whether the lung cancer was in the early or advanced stage. PMID:26883083

  7. POTENSI BAKTERI ASAM LAKTAT YANG DIISOLASI DARI BEKASAM SEBAGAI PENGHASIL ANGIOTENSIN CONVERTING ENZYME INHIBITOR PADA FERMENTASI “BEKASAM-LIKE” PRODUCT

    Directory of Open Access Journals (Sweden)

    Prima Retno Wikandari

    2013-03-01

    Full Text Available Potency of Lactic Acid Bacteria Isolated from Bekasam as Angiotensin Converting Enzyme Inhibitor Producing-Bacteria in Fermentation of “Bekasam-Like” Product Prima Retno Wikandari, Suparmo, Yustinus Marsono, Endang Sutriswati Rahayu 1Jurusan Kimia, Fakultas Matematika dan Ilmu Pengetahuan Alam, Universitas Negeri Surabaya, Gedung C3 Kampus Unesa,Ketintang, Surabaya 60231 2Jurusan Teknologi Pangan dan Hasil Pertanian, Fakultas Teknologi Pertanian, Universitas Gadjah Mada, Jl. Flora No. 1,Bulaksumur, Yogyakarta 55281 Email: wikandari@yahoo.com ABSTRAK Bekasam adalah salah satu produk ikan fermentasi tradisional. Produk ini diduga mempunyai aktivitas antihipertensiyang disebabkan oleh aktivitas peptida Angiotensin Converting Enzyme (ACE inhibitor yang dihasilkan dari degradasiproteolitik selama proses fermentasi bekasam. Bakteri asam laktat diduga berperan dalam degradasi proteolitikmenghasilkan peptida ACE inhibitor pada fermentasi bekasam. Sebanyak 6 strain bakteri asam laktat terpilih yangdiisolasi dari bekasam yaitu Lactobacillus plantarum B1765, L. plantarum T2565, L. plantarum N2352, L. plantarumB1465, Lactobacillus pentosus B2555, Pediococcus pentosaseus B1661 telah dikaji pertumbuhan, jumlah peptidayang terbentuk dari hasil degradasi proteolitik dan presentase penghambatannya terhadap aktivitas ACE selamafermentasi “bekasam-like” product. Semua strain dapat tumbuh dengan baik dan menunjukkan peningkatan jumlahpeptida dan peningkatan aktivitas penghambatan selama proses fermentasi yang bervariasi antar strain. Jumlah peptidatertinggi pada akhir proses fermentasi (8,55 ± 0,05 mg/g dihasilkan L. plantarum B1765 dan terkecil (4,45±0,10mg/g dihasilkan oleh P. pentosaceus B1661. L. plantarum B1765 juga menghasilkan aktivitas penghambatantertinggi (68,17±1,32%, diikuti oleh L. plantarum T2565 (62,54±2,11%, L. plantarum N2352 (61,56±1,32%, L.plantarum B1465 (59,85±1,58%, L. pentosus B2555 (56,61±4,28%, aktivitas penghambatan terkecil

  8. The angiotensin-converting enzyme inhibitor captopril inhibits poly(ADP-ribose)polymerase activation and exerts beneficial effects in an ovine model of burn and smoke injury

    Science.gov (United States)

    Asmussen, Sven; Bartha, Eva; Olah, Gabor; Sbrana, Elena; Rehberg, Sebastian W.; Yamamoto, Yusuke; Enkhbaatar, Perenlei; Hawkins, Hal K.; Ito, Hiroshi; Cox, Robert A.; Traber, Lillian D.; Traber, Daniel L.; Szabo, Csaba

    2011-01-01

    We investigated the effect of the angiotensin converting enzyme (ACE) inhibitor captopril in a clinically relevant ovine model of smoke and burn injury, with special reference to oxidative stress, activation of poly(ADP-ribose) polymerase in the lung and in circulating leukocytes. Female, adult sheep (28–40 kg) were divided into 3 groups. After tracheostomy and under deep anesthesia both vehicle-control (n=5) and captopril (20 mg/kg/d, iv., starting 0.5 hour before the injury) treated (n=5) groups were subjected to 2×20%, third degree burn injury and were insufflated with 48 breaths of cotton smoke. A sham group not receiving burn/smoke was also studied (n=5). Animals were mechanically ventilated and fluid resuscitated for 24 h in the awake state. Burn and smoke injury resulted in an upregulation of ACE in the lung, evidenced by immunohistochemical determination and Western blotting. Burn and smoke injury resulted in pulmonary dysfunction, as well as systemic hemodynamic alterations. Captopril treatment of burn and smoke animals improved PaO2/FiO2 ratio and pulmonary shunt fraction and reduced the degree of lung edema. There was a marked increase in PAR levels in circulating leukocytes after burn/smoke injury, which was significantly decreased by captopril. The pulmonary level of ACE and the elevated pulmonary levels of TGF-β in response to burn and smoke injury were significantly decreased by captopril treatment. Our results suggest that the ACE inhibitor captopril exerts beneficial effects on the pulmonary function in burn/smoke injury. The effects of the ACE inhibitor may be related to the prevention of ROS-induced PARP over-activation. ACE inhibition may also exert additional beneficial effects by inhibiting the expression of the pro-fibrotic mediator TGF-β. PMID:21701415

  9. The renoprotective effect of angiotensin-converting enzyme inhibitors in experimental chronic renal failure is not dependent on enhanced kinin activity.

    Science.gov (United States)

    Nabokov, A; Amann, K; Gassmann, P; Schwarz, U; Orth, S R; Ritz, E

    1998-01-01

    Angiotensin-converting enzyme (ACE) inhibitors have been shown to ameliorate the progression of glomerulosclerosis both in experimental models of uraemia and in patients with renal failure. It has not been documented, however, whether this is due to a decrease in angiotensin II generation or is a consequence of elevated local level of bradykinin. Morphometric investigation of renal tissue was performed in 5/6 nephrectomized (SNx) rats, i.e. untreated or treated with the ACE inhibitor ramipril (SNx-RAM), the B2 kinin receptor antagonist HOE 140 (SNx-HOE), or a combination of both (SNx-RAM + HOE) over 8 weeks. A further group of SNx received delayed treatment with ramipril from week 5 onward (SNx-RAMD). In addition, a sham-operated (SHAM) control group was studied. Systolic blood pressure was significantly lower in both SNx-RAM and SNx-RAM + HOE groups compared to (untreated) SNx. The glomerulosclerosis index (GSI) was substantially higher in the (untreated) SNx group (0.24 +/- 0.04) vs SHAM (0.02 +/- 0.01). A significantly higher GSI was found in the SNx-HOE group (0.45 +/- 0.08) as compared to (untreated) SNx. However, in the SNx-RAM, SNx-RAM + HOE, and SNx-RAMD groups, the GSI was lowered to a similar extent (0.1 +/- 0.02, 0.09 +/- 0.02, and 0.07 +/- 0.01 respectively). In addition, a concomitant attenuation of tubulointerstitial damage was noted in all the above groups. Increased kinin activity does not appear to play a major role in the renoprotective effect of ACE inhibitors in the remnant kidney model.

  10. Plasma levels of nitric oxide and related vasoactive factors following long-term treatment with angiotensin-converting enzyme inhibitor in patients with essential hypertension.

    Science.gov (United States)

    Kohno, M; Yokokawa, K; Minami, M; Yasunari, K; Maeda, K; Kano, H; Hanehira, T; Yoshikawa, J

    1999-10-01

    Several mechanisms other than the inhibition of systemic and local formation of angiotensin II (Ang II) have been proposed to play a role in mediating the hypotensive effects of angiotensin-converting enzyme (ACE) inhibitors. In the present study, we measured plasma levels of nitric oxide (NO) and the related vasoactive factors bradykinin, 6-keto prostaglandin F1alpha (6-keto PGF1alpha) a stable metabolite of prostacyclin, and cyclic guanosine-3',5'-monophosphate (cGMP) before and after a 4-week treatment with the ACE inhibitor lisinopril in 17 patients with essential hypertension. Plasma NO levels were measured by the Griess method after conversion of nitrate to nitrite. Long-term lisinopril treatment significantly reduced blood pressure and increased plasma NO and 6-keto PGF1alpha. The treatment also tended to increase plasma levels of bradykinin and cGMP, but not to a significant extent. The posttreatment NO level was inversely correlated with posttreatment systolic, diastolic, and mean blood pressure (n = 17, r= -.68, P< .01, n = 17, r= -.54, P < .05, and n = 17, r= -.66, P< .01, respectively). The posttreatment bradykinin level was also modestly correlated with posttreatment systolic and mean blood pressure (n = 17, r = -.51, P < .05 and n = 17, r = -.55, P < .05, respectively). In contrast, posttreatment 6-keto PGF1alpha and cGMP levels were not correlated with posttreatment systolic, diastolic, or mean blood pressure. These findings raise the possibility that increased formation of NO and bradykinin, as well as inhibition of the renin-angiotensin system, contribute to the hypotensive effect of the ACE inhibitor observed in our hypertensive patients.

  11. Does the new angiotensin converting enzyme inhibitor cilazapril prevent restenosis after percutaneous transluminal coronary angioplasty? Results of the MERCATOR study: a multicenter, randomized, double-blind placebo-controlled trial

    NARCIS (Netherlands)

    P.W.J.C. Serruys (Patrick); W.R. Rutsch (Wolfgang); N. Danchin (Nicolas); W. Wijns (William); H.U. Emanuelsson (Hakan); F. Chappuis; W.R.M. Hermans (Walter)

    1992-01-01

    textabstractBACKGROUND. Cilazapril is a novel angiotensin converting enzyme inhibitor with antiproliferative effects in the rat model after balloon injury. METHODS AND RESULTS. We conducted a randomized, double-blind placebo-controlled trial to assess the effect of cilazapril in angiographic resteno

  12. 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

    Institute of Scientific and Technical Information of China (English)

    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

  13. A comparative study of the prevalence of hyperkalemia with the use of angiotensin-converting enzyme inhibitors versus angiotensin receptor blockers

    Directory of Open Access Journals (Sweden)

    Seyed Ali Sadjadi

    2009-07-01

    Full Text Available Seyed Ali Sadjadi1, James I McMillan1, Navin Jaipaul1, Patricia Blakely1, Su Su Hline21Section of Nephrology (111N, Jerry L Pettis Memorial Veterans Medical Center, Loma Linda, CA, USA; 2Divison of Nephrology, Loma Linda University Medical Center, Loma Linda, CA, USABackground and objectives: Angiotensin-converting enzyme inhibitors (ACEI and angiotensin receptor blockers (ARB are increasingly used in a variety of settings including heart failure, renal failure, arterial hypertension, and diabetic nephropathy. The objective of this study was to investigate the prevalence of hyperkalemia with ACEI and ARB use, in a population of the United States veterans.Design, settings, material, and measurements: Retrospective observational cohort study of 1163 patients on ACEIs and 1168 patients on ARBs in a single Veterans Affairs Medical Center. Electronic medical records were reviewed over a 12-month period with data collected on various demographic, laboratory, comorbidity, and medication related variables. Results: Hyperkalemia (>5 mEq/L was observed in 20.4% of patients on ACEIs and 31.0% on ARBs. Severe hyperkalemia (6 mEq/L or higher, was observed in 0.8% of ACEI and 2.8% of ARB users. In univariate logistic regression analyses, diabetes mellitus; serum glucose, total carbon dioxide content, creatinine, and estimated glomerular filtration rate (GFR were significantly associated with hyperkalemia. ARB use, when compared to ACEI, was associated with a 42% increase in odds of hyperkalemia (odds ratio [OR] = 1.42; p = 0.001 in a model including adjustment for GFR and a 56% increase in odds of hyperkalemia (OR = 1.56; p < 0.001 in a model including adjustment for serum creatinine.Conclusions: Hyperkalemia, associated with the use of ACEIs and ARBs, is usually mild and severe hyperkalemia is rare. Hyperkalemia is more common with ARBs than ACEIs. ARB use, when compared to ACEI use, may significantly and independently be associated with increased odds of

  14. Sulfhydryl angiotensin-converting enzyme inhibitor promotes endothelial cell survival through nitric-oxide synthase, fibroblast growth factor-2, and telomerase cross-talk.

    Science.gov (United States)

    Donnini, Sandra; Terzuoli, Erika; Ziche, Marina; Morbidelli, Lucia

    2010-03-01

    The protective effect exerted by angiotensin-converting enzyme inhibitors (ACEI) in cardiovascular diseases caused by endothelial injury and aging has been attributed to the restoration of endothelial cell functions. Recently, we demonstrated a central role of the fibroblast growth factor-2 (FGF-2)/FGF receptor-1 system in mediating the acquisition of an angiogenic phenotype in coronary microvascular endothelium exposed to ACEI. Here, we report on the rescuing effect of ACEI on impaired endothelium and the intracellular signaling mechanisms that lead endothelial cells to enter apoptosis and to senesce. Conditions mimicking pathological cell damage (serum deprivation) lead to endothelial apoptosis as evidenced by increased caspase-3 activity. ACEI enhanced cell survival through activation of prosurvival and antiaging signals involving Akt phosphorylation, endothelial nitric-oxide synthase (eNOS) expression and activation, FGF-2 and telomerase catalytic subunit (TERT) up-regulation, and delayed senescence. In microvascular endothelial cells exposed to ACEI, Akt/eNOS pathway-dependent FGF-2 was necessary for gene transcription of TERT. These protective effects were particularly evident for sulfhydryl-containing ACEI (zofenoprilat), which were reported to exhibit potent antioxidant effects. In conclusion, ACEI with antioxidant properties up-regulate eNOS, FGF-2, and TERT mRNA, which favor endothelial cell survival and prolong their lifespan, thus restoring endothelial cell functions after vascular damage. These effects could explain the beneficial effects of these drugs in various cardiovascular diseases associated with endothelial injury and aging.

  15. An angiotensin converting enzyme inhibitor, benazepril can be transformed to an active metabolite, benazeprilat, by the liver of dogs with ascitic pulmonary heartworm disease.

    Science.gov (United States)

    Kitagawa, Hitoshi; Ohba, Yasunori; Kuwahara, Yasuhito; Ohne, Rieko; Kondo, Masahiro; Nakano, Masakazu; Sasaki, Yoshihide; Kitoh, Katsuya

    2003-06-01

    To examine whether an angiotensin converting enzyme (ACE) inhibitor, benazepril, can be transformed to the active metabolite, benazeprilat, by severely injured liver of dogs with ascitic heartworm disease, benazepril hydrochloride was administered orally to dogs once daily for 7 consecutive days at a dose rate of 0.29 mg/kg to 0.63 mg/kg of body weight, and plasma benazepril and benazeprilat concentrations were determined on the 1st and 7th administration days. In 7 dogs with ascitic pulmonary heartworm disease, plasma benazeprilat concentrations tended to be higher than in 7 control dogs both on the 1st and 7th administration days. The peak concentration and area under the concentration-time curve tended to be greater in dogs of the ascites group than in control dogs, but the statistics could not detect significant differences in the time to peak concentration and t(1/2) between the control and ascites groups. Plasma ACE activities decreased after administration of benazepril. In dogs with ascitic heartworm disease, benazepril was readily transformed to benazeprilat by the liver, and was effective for suppression of plasma ACE activity.

  16. [The investigation of angiotensin converting enzyme I/D and plasminogen activator inhibitor-1 4G/5G polymorphisms in venous thromboembolism patients].

    Science.gov (United States)

    Kaya, Halide; Karkucak, Mutlu; Salifoğlu, Hatice; Torun, Deniz; Kozan, Salih; Tunca, Yusuf

    2013-01-01

    Deep venous thrombosis and pulmonary embolism, known as venous thromboembolism and seen as a fairly common multifactorial diseases. Differ between populations due to genetic factors, several polymorphisms associated with venous thromboembolism was conducted. As a result of these studies the relationship between disease development and polymorphism is not clear yet. In this study we aimed to investigate the role of angiotensin converting enzyme insersion/deletion (ACE I/D) and plasminogen activator inhibitor-1 4G/5G (PAI-1 4G/5G) polymorphism in the development of disease. In our study, DNA isolated from 80 venous thromboembolism patients and 79 control groups was used. While the classical polymerase chain reaction method used to investigate the ACE I/D polymorphism, the polymerase chain reaction based on allele-specific amplification was used for the detection of PAI-1 4G/5G polymorphism. As a result, there were no significant statistical differences for ACE I/D and PAI-1 4G/5G polymorphism among patient and control groups (p> 0.05). These findings revealed that there is no relationship between these polymorphisms and the development of venous thromboembolism, but large-scale studies are need to be done.

  17. Angiotensin-Converting Enzyme Inhibitor Initiation and Dose Uptitration in Children With Cardiovascular Disease: A Retrospective Review of Standard Clinical Practice and a Prospective Randomized Clinical Trial.

    Science.gov (United States)

    Roche, S Lucy; Timberlake, Kathryn; Manlhiot, Cedric; Balasingam, Mervin; Wilson, Judith; George, Kristen; McCrindle, Brian W; Kantor, Paul F

    2016-05-20

    Angiotensin-converting enzyme inhibitors (ACEIs) are a mainstay of medical management in pediatric cardiology. However, there are no data defining how best to initiate and uptitrate the dose of these medications in children. Retrospective chart review revealed only 24% of our pediatric cardiology inpatients were discharged on predefined optimal doses of ACEIs and few underwent further dose uptitration in the 8 weeks after hospital discharge. Therefore, 2 alternative protocols for initiation of captopril were compared in a prospective randomized clinical trial. A "rapid uptitration" protocol reached an optimal dose on day 3, whereas the alternative, "prolonged uptitration" protocol, reached an optimal dose on day 9. Forty-6 patients (54% male) were recruited to the trial, with a median age of 0.7 year (IQR 0.5-2.3 years). Captopril was initiated while in intensive care in 39% of patients and on the cardiology ward in 61%. There were no differences between the protocols in episodes of hypotension, symptomatic hypotension, or indices of renal function. Patients following the rapid protocol reached higher doses of captopril (0.93±0.24 versus 0.57±0.38 mg/kg per dose, Ppractice or with a more prolonged protocol, rapid ACEI dose uptitration achieves a higher dosage in this population with no evident disadvantages. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00742040. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  19. Tumor growth-inhibitory effect of an angiotensin-converting enzyme inhibitor (captopril) in a lung cancer xenograft model analyzed using 18F-FDG-PET/CT.

    Science.gov (United States)

    Nakaya, Koji; Otsuka, Hideki; Kondo, Kazuya; Otani, Tamaki; Nagata, Motoi

    2016-02-01

    We administered an angiotensin-converting enzyme inhibitor (captopril) to mice implanted with a human lung adenocarcinoma epithelial cell line (A549 cells) and investigated the tumor growth-inhibitory effect of captopril from the viewpoint of glucose metabolism using (18)F-fluorodeoxyglucose ((18)F-FDG)-PET/CT. Subcutaneous implantation of A549 cells (1.9×10(6) cells) was carried out in the lower right flank of mice. Fifteen days after the transplantation of A549 cells, mice (six in each group) were treated with captopril (3.0 mg/mouse) or saline (1000 μl/mouse) for 5 days. We performed (18)F-FDG-PET/CT imaging of the mice before and after the treatment and evaluated the degree of (18)F-FDG accumulation in tumors. In both groups (the captopril-administrated and control groups), values for the metabolic tumor volume (MTV), maximum standardized uptake value, total lesion glycolysis, and tumor volume after treatment had a tendency to increase. However, tumor growth was suppressed in the captopril-administrated group compared with the control group. In terms of the growth rate, the MTV and tumor volume were significantly different (Pcaptopril exerted a potential tumor growth-inhibitory effect; this was because the captopril-administrated group showed low values of MTV, maximum standardized uptake value, total lesion glycolysis, and tumor volume in comparison with the control group.

  20. Angiotensin-converting enzyme inhibitors (ACEIs) and age-related maculopathy (ARM): cross-sectional findings from the Blue Mountains Eye Study.

    Science.gov (United States)

    Wu, Kathy H C; Wang, Jie Jin; Rochtchina, Elena; Foran, Suriya; Ng, Martin K C; Mitchell, Paul

    2004-06-01

    To assess the relationship between the use of angiotensin-converting enzyme inhibitors (ACEIs) and prevalence of age-related maculopathy (ARM). Eligible residents aged >/= 49 years were first examined in 1992-94 (Cross-section 1, n = 3654). Of these, 2335 were re-examined in 1997-99, together with an additional 1174 who became eligible after 1994 (Cross-section 2, n = 3509). Information regarding ACEI use was obtained and retinal photographs were graded using the Wisconsin ARM Grading System. In Cross-section 1, prevalence rates of late and early stage ARM were 1.3% and 4.3% among current ACEI users, and 2.0% and 4.8% among non-current users, respectively. In Cross-section 2, prevalence rates of late and early stage ARM were 2.3% and 11.3% among current ACEI users, and 1.3% and 9.3% among non-current users, respectively. After adjusting for age, sex and smoking, neither survey found any significant association between ACEI use and prevalence of either late or early ARM. No significant cross-sectional associations were found between ACEI use and ARM prevalence in this population.

  1. A Propensity-Matched Study of the Comparative Effectiveness of Angiotensin Receptor Blockers versus Angiotensin-Converting Enzyme Inhibitors in Heart Failure Patients Age ≥65 Years

    Science.gov (United States)

    Zhang, Yan; Fonarow, Gregg C.; Sanders, Paul W.; Farahmand, Firoozeh; Allman, Richard M.; Aban, Inmaculada B.; Love, Thomas E.; Levesque, Raynald; Kilgore, Meredith L.; Ahmed, Ali

    2011-01-01

    The comparative effectiveness of angiotensin-converting enzyme inhibitors (ACEIs) versus angiotensin receptor blockers (ARBs) in real-world older heart failure (HF) patients remains unclear. Of the 8049 hospitalized HF patients ≥65 years discharged alive from 106 Alabama hospitals, 4044 received discharge prescriptions of either ACEIs (n=3383) or ARBs (n=661). Propensity scores for ARB use, calculated for each of 4044 patients, were used to match 655 (99% of 661) patients receiving ARBs with 661 patients receiving ACEIs. The assembled cohort of 655 pairs of patients was well-balanced on 56 baseline characteristics. During over 8 years of follow-up, all-cause mortality occurred in 63% and 68% of matched patients receiving ARBs and ACEIs respectively (hazard ratio {HR} associated with ARB use, 0.86; 95% confidence interval {CI}, 0.75–0.99; p=0.031). Among the 956 matched patients with data on left ventricular ejection fraction (LVEF), the association between ARB (versus ACEI) use was significant only in 419 patients with LVEF≥45% (HR, 0.65; 95% CI, 0.51–0.84; p=0.001) but not in the 537 patients with LVEF ACEI) was associated with lower mortality and a trend toward lower HF hospitalization, findings which need replication in other HF populations. PMID:21890091

  2. Primary prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with end-stage renal disease undergoing dialysis.

    Science.gov (United States)

    Lin, Ting-Tse; Yang, Yao-Hsu; Liao, Min-Tsun; Tsai, Chia-Ti; Hwang, Juey J; Chiang, Fu-Tien; Chen, Pau-Chung; Lin, Jiunn-Lee; Lin, Lian-Yu

    2015-08-01

    Current evidence suggests that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reduce the incidence of new atrial fibrillation (AF) in a variety of clinical conditions, including the treatment of left ventricular dysfunction or hypertension. Here we assessed whether ACEIs and ARBs could decrease incidence of new-onset AF in patients with end-stage renal disease (ESRD). We identified patients from the Registry for Catastrophic Illness, a nation-wide database encompassing almost all of the patients receiving dialysis therapy in Taiwan from 1995 to 2008. Propensity score matching and Cox proportional hazards regression models were used to estimate hazard ratios for new-onset AF. Among 113,186 patients, 13% received ACEIs, 14% received ARBs therapy, and 9% received ACEIs or ARBs alternatively. After a median follow-up of 1524 days, the incidence of new-onset AF significantly decreased in patients treated with ACEIs (hazard ratio 0.587, 95% confidence interval 0.519-0.663), ARBs (0.542, 0.461-0.637), or ACEIs/ARBs (0.793, 0.657-0.958). The prevention of new-onset AF was significantly better in patients taking longer duration of ACEI or ARB therapy. The effect remained robust in subgroup analyses. Thus both ACEIs and ARBs appear to be effective in the primary prevention of AF in patients with ESRD. Hence, renin-angiotensin system inhibition may be an emerging treatment target for the primary prevention of AF.

  3. Comparative effectiveness of angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers for major renal outcomes in patients with diabetes: A 15-year cohort study.

    Science.gov (United States)

    Wu, Hon-Yen; Peng, Chiao-Ling; Chen, Pei-Chun; Chiang, Chih-Kang; Chang, Chee-Jen; Huang, Jenq-Wen; Peng, Yu-Sen; Tu, Yu-Kang; Chu, Tzong-Shinn; Hung, Kuan-Yu; Chien, Kuo-Liong

    2017-01-01

    Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are considered to have similar renoprotective effects; so far there has been no consensus about their priorities. This study aimed to compare ACEIs and ARBs for major renal outcomes and survival in a 15-year cohort of adults with diabetes. This study utilized Taiwan's medical and pharmacy claims data in the Longitudinal Cohort of Diabetes Patients. The primary outcome was long-term dialysis, and secondary outcomes were hospitalization for acute kidney injury, hospitalization for hyperkalemia, all-cause death, cardiovascular death, and non-cardiovascular death. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes comparing ACEIs with ARBs. We conducted subgroup analyses and interaction tests among patients with different age and comorbid diseases. A total of 34,043 patients received ACEIs and 23,772 patients received ARBs. No differences were found for primary or secondary outcomes in the main analyses. ACEIs showed significantly lower hazard than ARBs for long-term dialysis among patients with cardiovascular disease (HR 0.80, 95% CI 0.66-0.97, interaction P = 0.003) or chronic kidney disease (0.81, 0.71-0.93, interaction P = 0.001). Our analyses show similar effects of ACEIs and ARBs in patients with diabetes. However, ACEIs might provide additional renoprotective effects among patients who have cardiovascular disease or chronic kidney disease.

  4. Pharmacogenetic effects of angiotensin-converting enzyme inhibitors over age-related urea and creatinine variations in patients with dementia due to Alzheimer disease.

    Science.gov (United States)

    Ferreira de Oliveira, Fabricio; Berretta, Juliana Marília; Suchi Chen, Elizabeth; Cardoso Smith, Marilia; Ferreira Bertolucci, Paulo Henrique

    2016-06-30

    Renal function declines according to age and vascular risk factors, whereas few data are available regarding genetically-mediated effects of anti-hypertensives over renal function. To estimate urea and creatinine variations in dementia due to Alzheimer disease (AD) by way of a pharmacogenetic analysis of the anti-hypertensive effects of angiotensin-converting enzyme inhibitors (ACEis). Consecutive outpatients older than 60 years-old with AD and no history of kidney transplant or dialytic therapy were recruited for prospective correlations regarding variations in fasting blood levels of urea and creatinine in one year, considering ACE genotypes of rs1800764 and rs4291 and their respective haplotypes, and treatment with ACEis along with blood pressure variations. For 190 patients, 152 had arterial hypertension, and 122 used ACEis. Minor allele frequencies were 0.492 for rs1800764-C and 0.337 for rs4291-T, both in Hardy-Weinberg equilibrium. There were no overall significant yearly variations in levels of urea and creatinine, but their concurrent variations were positively correlated (ρ ACEis was protective regarding creatinine variations. The use of ACEis was also protective for carriers of rs1800764-CT/rs4291-AA, while carriers of rs1800764-CT/rs4291-AT had steeper reductions in creatinine levels, particularly when they were treated with ACEis. Effects of ACEis over creatinine variations are genetically mediated and independent of blood pressure variations in older people with AD.

  5. Impact of the additive effect of angiotensin-converting enzyme inhibitors and /or statins with antiplatelet medication on mortality after acute ischaemic stroke.

    Science.gov (United States)

    Hassan, Yahaya; Al-Jabi, Samah W; Aziz, Noorizan Abd; Looi, Irene; Zyoud, Sa'ed H

    2012-04-01

    There has been recent interest in combining antiplatelets, angiotensin-converting enzyme inhibitors (ACEIs) and statins in primary and secondary ischaemic stroke prevention. This observational study was performed to evaluate the impact of adding ACEIs and/or statins to antiplatelets on post-stroke in-hospital mortality. Ischaemic stroke patients attending a hospital in Malaysia over an 18-month period were evaluated. Patients were categorized according to their vital status at discharge. Data included demographic information, risk factors, clinical characteristics and previous medications with particular attention on antiplatelets, ACEIs and statins. In-hospital mortality was compared among patients who were not taking antiplatelets, ACEIs or statins before stroke onset versus those who were taking antiplatelets alone or in combination with either ACEIs, statins or both. Data analysis was performed using SPSS version 15. Overall, 637 patients met the study inclusion criteria. After controlling for the effects of confounders, adding ACEIs or statins to antiplatelets significantly decreased the incidence of death after stroke attack by 68% (p = 0.036) and 81% (p = 0.010), respectively, compared to patients on antiplatelets alone or none of these medications. Additionally, the addition of both ACEIs and statins to antiplatelet medication resulted in the highest reduction (by 94%) of the occurrence of death after stroke attack (p rate of ischaemic stroke morbidity and mortality by enhancing the application of specific therapeutic and management strategies for patients at a high risk of acute stroke.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  7. Fosinopril and zofenopril, two angiotensin-converting enzyme (ACE) inhibitors, potentiate the anticonvulsant activity of antiepileptic drugs against audiogenic seizures in DBA/2 mice.

    Science.gov (United States)

    Sarro, Giovambattista De; Paola, Eugenio Donato Di; Gratteri, Santo; Gareri, Pietro; Rispoli, Vincenzo; Siniscalchi, Antonio; Tripepi, Giovanni; Gallelli, Luca; Citraro, Rita; Russo, Emilio

    2012-03-01

    The renin-angiotensin system (RAS) exists in the brain and it may be involved in pathogenesis of neurological and psychiatric disorders including seizures. The aim of the present research was to evaluate the effects of some angiotensin-converting enzyme inhibitors (ACEi; captopril, enalapril, fosinopril and zofenopril), commonly used as antihypertensive agents, in the DBA/2 mice animal model of generalized tonic-clonic seizures. Furthermore, the co-administration of these compounds with some antiepileptic drugs (AEDs; carbamazepine, diazepam, felbamate, gabapentin, lamotrigine, phenobarbital, phenytoin, topiramate and valproate) was studied in order to identify possible positive interactions in the same model. All ACEi were able to decrease the severity of audiogenic seizures with the exception of enalapril up to the dose of 100mg/kg, the rank order of activity was as follows: fosinopril>zofenopril>captopril. The co-administration of ineffective doses of all ACE inhibitors with AEDs, generally increased the potency of the latter. Fosinopril was the most active in potentiating the activity of AEDs and the combination of ACEi with lamotrigine and valproate was the most favorable, whereas, the co-administrations with diazepam and phenobarbital seemed to be neutral. The increase in potency was generally associated with an enhancement of motor impairment, however, the therapeutic index of combined treatment of AEDs with ACEi was predominantly more favorable than control. ACEi administration did not influence plasma and brain concentrations of the AEDs studied excluding pharmacokinetic interactions and concluding that it is of pharmacodynamic nature. In conclusion, fosinopril, zofenopril, enalapril and captopril showed an additive anticonvulsant effect when co-administered with some AEDs, most notably carbamazepine, felbamate, lamotrigine, topiramate and valproate, implicating a possible therapeutic relevance of such drug combinations.

  8. Effect of angiotensin-converting enzyme inhibitor on left ventricular parameters and circulating brain natriuretic peptide in elderly hypertensives with left venticular hypertrophy.

    Science.gov (United States)

    Kohno, M; Minami, M; Kano, H; Yasunari, K; Maeda, K; Hanehira, T; Yoshikawa, J

    2000-10-01

    In the elderly, left ventricular hypertrophy (LVH) is a powerful risk factor for cardiovascular events and cardiovascular death. The purpose of the present study is to investigate the effect of long-term effective blood pressure control with the angiotensin-converting enzyme (ACE) inhibitor temocapril on left ventricular (LV) mass and function indices and the circulating concentration of the cardiac hormone brain natriuretic peptide (BNP) in elderly hypertensives with LVH. Temocapril treatment was administered for 1 year to 11 elderly hypertensives (mean age, 72 years) with LVH. Cardiac dimensions and circulating concentrations of BNP were monitored before initiation of treatment and after 1 year of treatment. At entry, BNP levels were positively correlated with the LV mass index, but were not correlated with the mean blood pressure, LV ejection fraction, or E/A ratio (the ratio of peak transmitral flow velocity in early diastole, peak E, to that in late diastole, peak A). After 1 year, temocapril treatment resulted in effective control of blood pressure. The treatment did not affect the LV ejection fraction, but modestly increased the E/A ratio. Temocapril significantly reduced septal and posterior wall thickness and the LV mass index. BNP significantly declined after 1 year. Changes in BNP were significantly related to changes in the LV mass index, but were not related to changes in the mean blood pressure, LV ejection fraction, or E/A ratio. The results suggest that long-term ACE inhibitor treatment with temocapril can induce the regression of LV mass and reduce elevated plasma BNP in elderly hypertensive patients with LVH. In this study, changes in BNP reflected the magnitude of regression of LVH.

  9. Effect of angiotensin II type 1 receptor blocker and angiotensin converting enzyme inhibitor on the intraocular growth factors and their receptors in streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Ik Soo Byon

    2017-06-01

    Full Text Available AIM: To investigate the effect of angiotensin II type 1 receptor blocker (ARB and angiotensin converting enzyme inhibitor (ACEI on intraocular growth factors and their receptors in streptozotocin-induced diabetic rats. METHODS: Forty Sprague-Dawley rats were divided into 4 groups: control, diabetes mellitus (DM, candesartan-treated DM, and enalapril-treated DM (each group, n=10. After the induction of DM by streptozotocin, candesartan [ARB, 5 mg/(kg·d] and enalapril [ACEI, 10 mg/(kg·d] were administered to rats orally for 4wk. Vascular endothelial growth factor (VEGF and angiotensin II (Ang II concentrations in the vitreous were measured using enzyme-linked immunosorbent assays, and VEGF receptor 2 and angiotensin II type 1 receptor (AT1R levels were assessed at week 4 by Western blotting. RESULTS: Vitreous Ang II levels were significantly higher in the DM group and candesartan-treated DM group than in the control (P=0.04 and 0.005, respectively. Vitreous AT1R increased significantly in DM compared to the other three groups (P<0.007. Candesartan-treated DM rats showed higher vitreal AT1R concentration than the enalapril-treated DM group and control (P<0.001 and P=0.005, respectively. No difference in vitreous Ang II and AT1R concentration was found between the enalapril-treated DM group and control. VEGF and its receptor were below the minimum detection limit in all 4 groups. CONCLUSION: Increased Ang II and AT1R in the hyperglycemic state indicate activated the intraocular renin-angiotensin system, which is inhibited more effectively by systemic ACEI than systemic ARB.

  10. General pharmacology of the novel angiotensin converting enzyme inhibitor alacepril. 2nd communication: Effects on central nervous and sensory systems and on the other functions.

    Science.gov (United States)

    Matsuno, Y; Hori, H; Oka, M; Nakamura, H; Ito, T; Kadokawa, T

    1986-01-01

    The effects of 1-[(S)-3-acetylthio-2-methylpropanoyl]-L-prolyl-L-phenylalanine (alacepril, DU-1219), an orally active angiotensin converting enzyme inhibitor, on the central nervous and sensory systems and on several other functions were compared with those of captopril in the experimental animals. Alacepril at the high oral dose of 600 mg/kg prolonged the hexobarbital sleeping time and potentiated the reserpine-induced hypothermia in mice. However, alacepril at the same dose did not affect the general behavior, convulsions induced by maximal electroshock, pentetrazol and strychnine, active avoidance in mice and body temperature in rats. In addition, alacepril (200 mg/kg i.v.) has little effect on general behavior in mice. Captopril at over 107 mg/kg p.o. produced eyelid closure and at 320 mg/kg prolonged the hexobarbital sleeping time. A metabolite of alacepril, desacetylalacepril (DU-1227) (200 mg/kg i.v.), caused salivation in mice. Alacepril and DU-1227 at 60 mg/kg i.v. were without effect on flexor reflex and spontaneous electroencephalogram (EEG) in cats, while captopril at the equimolar dose depressed the flexor reflex and showed a tendency to increase the beta 2-band relative power of the cortical EEG. Alacepril and captopril neither affected the writhing syndrome induced by acetic acid nor that by phenylquinone in mice. Local anesthetic and irritant activities in rabbits and effect on neuromuscular junction in anesthetized rats were not observed with the two compounds. Alacepril at the oral dose of 0.1 mg/kg potentiated the carrageenin-induced edema in rats. However, the effect was one third that of captopril. Alacepril and captopril did not affect the increased vascular permeability by acetic acid in mice.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers on lymphangiogenesis of gastric cancer in a nude mouse model

    Institute of Scientific and Technical Information of China (English)

    WANG Liang; CAI Shi-rong; ZHANG Chang-hua; HE Yu-long; ZHAN Wen-hua; WU Hui; PENG Jian-jun

    2008-01-01

    Background Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) can inhibit tumor growth by inhibition of angiogenesis.This study was designed to study the anticancer effects of ACEI and ARB on tumor growth and lymphangiogenesis in an implanted gastric cancer mouse model.Methods A model of gastric cancer was established by subcutaneously inoculating human gastric cancer cell line SGC-7901 into 60 nude mice.One week later,all mice were randomly divided into 5 groups.A control group received physiologic saline once daily for 21 days.Mice in the 4 treatment groups received one of the following agents by gavage once daily for 21 days:perindopril,2 mg/kg;captopril,5 mg/kg;Iosartan,50 mg/kg;or valsartan,40 mg/kg.Twenty-one clays after treatment,all the mice were sacrificed and the tumors were removed.Tumor sections were processed,and immunohistochemical methods were used to observe the expressions of vascular endothelial growth factor C (VEGF-C),matrix metalloproteinase 7 (MMP-7),and lymphatic microvessel density (LMVD).Results Tumor volume was significantly inhibited in all ACEI and ARB groups,compared with the control group (all P <0.01).LMVD in the ACEI and ARB groups was also significantly lower than that of the control group (all P<0.01).In the ACEI groups,the expressions of VEGF-C and MMP-7 were both significantly decreased,compared with the control group (all P<0.05).In the ARB groups,expression of VEGF-C was significantly decreased compared with the control group (all P<0.05).However,no significant difference was found in the expression of MMP-7 between ARB groups and the control group.Conclusion In a mouse model,ACEI and ARB might inhibit gastric cancer tumor growth by suppressing lymphangiogenesis.

  12. Prevention of Trastuzumab and Anthracycline-induced Cardiotoxicity Using Angiotensin-converting Enzyme Inhibitors or β-blockers in Older Adults With Breast Cancer.

    Science.gov (United States)

    Wittayanukorn, Saranrat; Qian, Jingjing; Westrick, Salisa C; Billor, Nedret; Johnson, Brandon; Hansen, Richard A

    2017-05-23

    Although clinical trials have provided some data on the benefit of angiotensin-converting enzyme inhibitors (ACEIs) or β-blockers (BBs) in patients with chemotherapy-induced cardiotoxicity, evidence of ACEIs/BBs on prevention of trastuzumab and/or anthracycline-induced cardiotoxicity outside trials is limited. A cohort study of 142,990 women (66 y and above) newly diagnosed with breast cancer from 2001 to 2009 was conducted using the Surveillance, Epidemiology, and End Results-Medicare-linked database. The ACEI/BB exposure was defined as filled prescription(s) before or after the initiation of trastuzumab/anthracyclines. The nonexposed group was defined as those who had never been prescribed ACEIs/BBs. Cumulative rates of cardiotoxicity and all-cause mortality were estimated and marginal structural Cox models were used to determine factors associated with cardiotoxicity and all-cause mortality adjusting for baseline covariates and use of chemotherapy. All statistical tests were 2 sided. The final sample included 6542 women. Adjusted hazard ratio for cardiotoxicity and all-cause mortality for the ACEI/BB exposed group were 0.77 (95% confidence interval, 0.62-0.95) and 0.79 (95% confidence interval, 0.70-0.90) compared with the nonexposed group, respectively. Starting ACEIs/BBs≤6 months after the initiation of trastuzumab/anthracyclines and having exposed duration≥6 months were also associated with decreased risk of cardiotoxicity and all-cause mortality. Baseline characteristics, including age, non-Hispanic black, advanced cancer, region, comorbidity, preexisting cardiovascular conditions, lower socioeconomic status, and concomitant treatment were significantly associated with an elevated risk of all-cause mortality and/or cardiotoxicity (all PACEIs/BBs show favorable effects on preventing cardiotoxicity and improving survival in female breast cancer patients undergoing trastuzumab/anthracycline treatment.

  13. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in patients with abdominal aortic aneurysms: nation-wide cohort study.

    Science.gov (United States)

    Kristensen, Karl Emil; Torp-Pedersen, Christian; Gislason, Gunnar Hilmar; Egfjord, Martin; Rasmussen, Henrik Berg; Hansen, Peter Riis

    2015-03-01

    The renin-angiotensin system is thought to play a pivotal role in the pathogenesis of abdominal aortic aneurysms (AAAs). However, effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs) on human AAAs remain unclear. We therefore examined whether treatment with ACEIs or ARBs influenced hard clinical end points in a nation-wide cohort of patients with AAA. All patients diagnosed with AAA during the period 1995 to 2011 were identified from the Danish nation-wide registries. Subjects were divided according to ACEI and ARB treatment status and followed up for an average of 5 years. Study outcomes were evaluated by time-dependent Cox proportional hazard models. Of 9441 patients with AAA, 12.6% were treated with ACEIs and 5.0% received ARBs. Incidence rates of death from AAA per 100 patient-years were 3.7, 3.6, 4.0, and 4.7 for treatment with ACEIs or ARBs, ACEIs, ARBs, and no ACEI/ARB, respectively. Hazard ratios of death from AAA were 0.64 (95% confidence interval, 0.51-0.80; PACEIs and 0.65 (95% confidence interval, 0.48-0.88; P=0.006) for those receiving ARBs, respectively (P for difference=0.944). The risk of surgery for AAA was significantly reduced in patients receiving ACEIs (hazard ratio, 0.86 [95% confidence interval, 0.74-0.99]; P=0.040) but not in patients receiving ARBs (hazard ratio, 1.02 [95% confidence interval, 0.84-1.23]; P=0.867; P for difference=0.119). In this observational study, treatment with ACEIs or ARBs was associated with a comparable reduction in mortality but not in surgery for AAA among patients with AAA. Randomized controlled trials are warranted to confirm these findings. © 2015 American Heart Association, Inc.

  14. Mortality benefit of long-term angiotensin-converting enzyme inhibitors or angiotensin receptor blockers after successful percutaneous coronary intervention in non-ST elevation acute myocardial infarction.

    Science.gov (United States)

    González-Cambeiro, María Cristina; López-López, Andrea; Abu-Assi, Emad; Raposeiras-Roubín, Sergio; Peña-Gil, Carlos; García-Acuña, José; González-Juanatey, Ramón

    2016-12-01

    Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been shown to reduce mortality after myocardial infarction (MI). Current guidelines recommend their prescription in all patients after MI. Limited data are available on whether ACEIs/ARBs still improve prognosis in the contemporary era of non-ST elevation MI (NSTEMI) management. We aimed to evaluate the mortality benefit of ACEIs/ARBs in NSTEMI patients treated successfully with percutaneous coronary intervention (PCI). We analyzed 2784 patients with NSTEMI treated successfully with in-hospital PCI. Two groups were formed based on ACEI/ARB prescription at discharge. Two propensity score (PS) analyses were performed to control for differences in covariates: one with adjustment among the entire cohort, and the other with PS matching (n=1626). The outcome variable was all-cause mortality at four-year follow-up. There were 1902 (68.3%) patients prescribed ACEIs/ARBs at discharge. When adjusted by PS, ACEI/ARB use was associated with a hazard ratio (HR) for mortality of 0.75 (0.60-0.94; absolute risk reduction [ARR] 4.0%) in the whole cohort (p=0.01). After one-to-one PS matching (n=813 in each group), the mortality rate was significantly lower in patients prescribed ACEIs/ARBs, with HR of 0.77 (0.63-0.94; ARR 3.8%) (p=0.03). In this observational study of patients with NSTEMI, all of them treated successfully by PCI, the use of ACEIs/ARBs was significantly associated with a lower risk of four-year all-cause mortality. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Terms of Major Cardiovascular Disease Outcomes in Elderly Patients

    Science.gov (United States)

    Chien, Shu-Chen; Ou, Shuo-Ming; Shih, Chia-Jen; Chao, Pei-Wen; Li, Szu-Yuan; Lee, Yi-Jung; Kuo, Shu-Chen; Wang, Shuu-Jiun; Chen, Tzeng-Ji; Tarng, Der-Cherng; Chu, Hsi; Chen, Yung-Tai

    2015-01-01

    Abstract Renin and aldosterone activity levels are low in elderly patients, raising concerns about the benefits and risks of angiotensin-converting-enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARB) use. However, data from direct comparisons of the effects of ACEIs on ARBs in the elderly population remain inconclusive. In this nationwide study, all patients aged ≥ 70 years were retrieved from the Taiwan National Health Insurance database for the period 2000 to 2009 and were followed up until the end of 2010. The ARB cohort (12,347 patients who continuously used ARBs for ≥ 90 days) was matched to ACEI cohort using high-dimensional propensity score (hdPS). Intention-to-treat (ITT) and as-treated (AT) analyses were conducted. In the ITT analysis, after considering death as a competing risk, the ACEI cohort had similar risks of myocardial infarction (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.79–1.06), ischemic stroke (HR 0.98, 95% CI 0.90–1.07), and heart failure (HR 0.93, 95% CI 0.83–1.04) compared with the ARB cohort. No difference in adverse effects, such as acute kidney injury (HR 0.99, 95% CI 0.89–1.09) and hyperkalemia (HR 1.02, 95% CI 0.87–1.20), was observed between cohorts. AT analysis produced similar results to those of ITT analysis. We were unable to demonstrate a survival difference between cohorts (HR 1.03, 95% CI 0.88–1.21) after considering drug discontinuation as a competing risk in AT analysis. Our study supports the notion that ACEI and ARB users have similar risks of major adverse cardiovascular events (MACE), even in elderly populations. PMID:26512568

  16. Association between exposure to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers prior to septic shock and acute kidney injury.

    Science.gov (United States)

    Suberviola, B; Rodrigo, E; González-Castro, A; Serrano, M; Heras, M; Castellanos-Ortega, Á

    To evaluate the association between angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) use prior to a septic shock episode and the development, prognosis and long-term recovery from acute kidney injury (AKI). A single-centre, prospective observational study was carried out between September 2005 and August 2010. Patients admitted to the ICU of a third level hospital. A total of 386 septic shock patients were studied. None. Use of ACEIs/ARBs, AKI development, recovery of previous creatinine levels and time to recovery. A total of 386 patients were included, of which 312 (80.8%) developed AKI during ICU stay and 23% were receiving ACEIs/ARBs. The percentage of patients on ACEIs/ARBs increased significantly in relation to more severe stages of AKI irrespective of the kind of AKI score. After adjusting for confounders, the development of AKI was independently associated to the use of ACEIs/ARBs (OR 2.19; 95%CI 1.21-3.84; p=.04). With respect to the recovery of kidney function, the group of patients on ACEIs/ARBs had significantly higher creatinine levels at ICU discharge and needed hemodialysis more frequently thereafter. However, use of ACEIs/ARBs affected neither recovery of previous creatinine levels nor significantly delayed recovery. The use of ACEIs/ARBs before septic shock episodes was correlated to AKI development and severity, but did not affect the recovery of kidney function after sepsis resolution. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  17. A meta-analytical comparison of atenolol with angiotensin-converting enzyme inhibitors on arterial stiffness, peripheral blood pressure and heart rate in hypertensive patients.

    Science.gov (United States)

    Xie, Hong; Luo, Gaoqing; Zheng, Yong; Peng, Feng; Xie, Liangdi

    2017-01-01

    This meta-analysis of randomized parallel controlled trials was designed to compare the efficacy of atenolol with angiotensin-converting enzyme inhibitors (ACEIs) in changing pulse wave velocity (PWV), peripheral blood pressure and heart rate (HR) among patients with essential hypertension. This study was conducted according to the PRISMA guideline. Data collection was independently completed by two investigators. Statistical analyses were completed by Stata software (v12.0). Eight clinical trials were meta-analyzed in this study. Overall changes in PWV (weighted mean difference or WMD = 0.068, 95% confidence interval or CI: -0.487 to -0.623, P = 0.811) and peripheral systolic blood pressure (PSBP) (WMD = -1.281 mmHg, 95% CI: -6.936 to 4.375, P = 0.657) did not differ significantly between atenolol and ACEIs treatment. Relative to ACEIs, atenolol had a more favorable impact on peripheral diastolic blood pressure (PDBP) (WMD = -1.912 mmHg, 95% CI: -3.732 to -0.091, P = 0.040) and HR (WMD = -9.23 bpm, 95% CI: -12.53 to -5.93, P ACEIs within early 3-month treatment in PSBP (WMD = -4.097 mmHg, 95% CI: -6.589 to -1.605, P = 0.001), PDBP (WMD = -6.802 mmHg, 95% CI: -8.517 to -5.087, P ACEIs were equally effective in reducing PWV and PSBP, while atenolol was superior over ACEIs in improving PDBP and HR, especially within short-term treatment.

  18. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers have no beneficial effect on ablation outcome in chronic persistent atrial fibrillation.

    Science.gov (United States)

    Zheng, Bin; Kang, Junping; Tian, Ying; Tang, Ribo; Long, Deyong; Yu, Ronghui; He, Hua; Zhang, Ming; Shi, Lisheng; Tao, Hailong; Liu, Xingpeng; Dong, Jianzeng; Ma, Changsheng

    2009-06-01

    Previous studies have shown that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) could reverse structural and electrical atria remodelling and decrease atrial fibrillation (AF) onset or recurrence. The aim of this retrospective study was to investigate whether ACEIs/ARBs had beneficial effects on ablation outcome of chronic persistent AF. This study included 139 patients with chronic persistent AF who underwent radiofrequency ablation in our centre. Patients were divided into an ACEIs/ARBs group or a non-ACEIs/ARBs group. During follow-up (14.6 +/- 8.9 months) after AF ablation, AF-free survival in the ACEIs/ARBs group was not significantly different from the non-ACEIs/ARBs group (P = 0.339). Univariate analysis showed that predictors for AF-free survival were AF history (HR, 1.064; 95% CI, 1.021-1.108; P = 0.003) and duration of chronic persistent AF (HR, 1.012; 95% CI, 1.005-1.019; P = 0.001). Multivariate analysis showed that predictors for AF-free survival were AF history (HR, 1.051; 95% CI, 1.004-1.101; P = 0.035) and duration of chronic persistent AF (HR, 1.012; 95% CI, 1.004-1.020; P = 0.004). ACEIs/ARBs therapy was not a predictor for AF-free survival neither in univariate nor multivariate analysis. In this observational study, no effect of ACEIs or ARBs was seen on the AF recurrence after ablation of chronic persistent AF.ACEIs/ARBs did not help to predict a better ablation outcome. Predictors for ablation outcome are AF history and duration of chronic persistent AF.

  19. The Incidence and Risk of Biochemical Recurrence Following Radical Radiotherapy for Prostate Cancer in Men on Angiotensin-Converting Enzyme Inhibitors (ACEIs) or Angiotensin Receptor Blockers (ARBs).

    Science.gov (United States)

    Alashkham, Abduelmenem; Paterson, Catherine; Windsor, Phyllis; Struthers, Allan; Rauchhaus, Petra; Nabi, Ghulam

    2016-10-01

    Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are linked to prostate cancer, but their effect on biochemical recurrence (BR) remains unknown. Our aims were to investigate the incidence and risk of BR in men on ACEIs/ARBs after radical radiotherapy with adjuvant∖neoadjuvant hormone treatment. A propensity score analysis of 558 men was conducted. Men were stratified into 3 groups: hypertensive men on ACEIs/ARBs (as a study group), non-hypertensive men not on ACEIs/ARBs, and hypertensive men not on ACEIs/ARBs (both as a control group). The multivariate analysis of variance, chi-square, Kruskal-Wallis, analysis of variance, risk ratio, confidence interval, Kaplan-Meier plots, and log-rank tests were used. The mean age and follow-up were 68.51 and 3.33 years, respectively. There was a statistically significant difference in the prevalence of BR among the treatment groups (P ACEIs/ARBs than in non-hypertensive men not taking ACEIs/ARBs (P ACEIs/ARBs (P ACEIs/ARBs than in non-hypertensive men not taking ACEIs/ARBs (P ACEIs/ARBs was significantly lower than in the group of non-hypertensive men not taking ACEIs/ARBs (RR, 0.74; 95% CI, 0.64-0.86; P ACEIs/ARBs (RR, 0.78; 95% CI, 0.67-0.91; P ACEIs/ARBs was significantly different compared with the control groups (P ACEIs/ARBs had significantly lower incidence of BR after radical radiotherapy with hormone treatment. The intake of ACEIs/ARBs was associated with reduced risk of BR. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Angiotensin converting enzyme inhibitors for prevention of new-onset type 2 diabetes mellitus: a meta-analysis of 72,128 patients.

    Science.gov (United States)

    Geng, Deng-feng; Jin, Dong-mei; Wu, Wei; Liang, Yong-de; Wang, Jing-feng

    2013-09-10

    Angiotensin converting enzyme inhibitors (ACEIs) have been linked to reduced risk of new-onset diabetes, but the evidence was insufficient. The aim of this study was to evaluate the effect of ACEIs on the development of new-onset type 2 diabetes. Randomized controlled trials (RCTs) about ACEIs and new-onset diabetes were identified by electronic and manual searches. Nine RCTs with 92,404 patients (72,128 non-diabetic patients at baseline) were included in this study. Compared with control group, incidence of new-onset diabetes was significantly reduced in the ACEIs group [OR 0.80, (0.71, 0.91)], irrespective of achieved blood pressure levels at the follow-up. ACEIs therapy was associated with significant reduction in the risk of new-onset diabetes compared with beta-blockers/diuretics [OR 0.78, (0.65, 0.93)], placebo [OR 0.79, (0.64, 0.96)], or calcium channel blockers [OR 0.85, (0.73, 0.99)]. ACEIs treatment was associated with significant reduction in the risk of new-onset diabetes in patients with hypertension [OR 0.80, (0.68, 0.93)], coronary artery disease (CAD) or cardiovascular disease [OR 0.83, (0.68, 1.00)], or heart failure [OR 0.22, (0.10, 0.47)]. Among patients with impaired glucose tolerance or impaired fasting glucose, ramipril did not significantly reduce the incidence of diabetes [OR 0.91, (0.79, 1.05)], but significantly increased regression to normoglycemia. ACEIs have beneficial effects in preventing new-onset diabetes. ACEIs provide additional benefits of lowering the risk of new-onset diabetes in patients with hypertension, CAD or other cardiovascular disease. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

    Huang, Shiou-Huei; Hsu, Chien-Ning; Yu, Shu-Hui; Cham, Thau-Ming

    2012-05-31

    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. 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. 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 ACEIs after 2004 price adjustment (-156.9%, p ACEIs to ARBs within individuals is evident. Policy makers should reconsider the appropriateness of the current adjustment strategies applied to

  2. Effect of angiotensin-converting enzyme inhibitors and receptor blockers on appropriate implantable cardiac defibrillator shock in patients with severe systolic heart failure (from the GRADE Multicenter Study).

    Science.gov (United States)

    AlJaroudi, Wael A; Refaat, Marwan M; Habib, Robert H; Al-Shaar, Laila; Singh, Madhurmeet; Gutmann, Rebecca; Bloom, Heather L; Dudley, Samuel C; Ellinor, Patrick T; Saba, Samir F; Shalaby, Alaa A; Weiss, Raul; McNamara, Dennis M; Halder, Indrani; London, Barry

    2015-04-01

    Sudden cardiac death (SCD) is a leading cause of mortality in patients with cardiomyopathy. Although angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) decrease cardiac mortality in these cohorts, their role in preventing SCD has not been well established. We sought to determine whether the use of ACEi or ARB in patients with cardiomyopathy is associated with a lower incidence of appropriate implantable cardiac defibrillator (ICD) shocks in the Genetic Risk Assessment of Defibrillator Events study that included subjects with an ejection fraction of ≤30% and ICDs. Treatment with ACEi/ARB versus no-ACEi/ARB was physician dependent. There were 1,509 patients (mean age [SD] 63 [12] years, 80% men, mean [SD] EF 21% [6%]) with 1,213 (80%) on ACEi/ARB and 296 (20%) not on ACEi/ARB. We identified 574 propensity-matched patients (287 in each group). After a mean (SD) of 2.5 (1.9) years, there were 334 (22%) appropriate shocks in the entire cohort. The use of ACEi/ARB was associated with lower incidence of shocks at 1, 3, and 5 years in the matched cohort (7.7%, 16.7%, and 18.5% vs 13.2%, 27.5%, and 32.0%; RR = 0.61 [0.43 to 0.86]; p = 0.005). Among patients with glomerular filtration rate (GFR) >60 and 30 to 60 ml/min/1.73 m(2), those on no-ACEi/ARB were at 45% and 77% increased risk of ICD shock compared with those on ACEi/ARB, respectively. ACEi/ARB were associated with significant lower incidence of appropriate ICD shock in patients with cardiomyopathy and GFR ≥30 ml/min/1.73 m(2) and with neutral effect in those with GFR <30 ml/min/1.73 m(2).

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

    Directory of Open Access Journals (Sweden)

    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

  4. The risk of hypertension after preoperative discontinuation of angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists in ambulatory and same-day admission patients.

    Science.gov (United States)

    Twersky, Rebecca S; Goel, Vasudha; Narayan, Preeti; Weedon, Jeremy

    2014-05-01

    The continued use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II subtype I receptor antagonists (ARBs) medications in the preoperative period has been reported to be associated with intraoperative hypotension that can be unresponsive to pressor drugs. As a result, several investigators suggested discontinuation of these medications before scheduled surgery but did not report on unintended consequences that might result from discontinuation. We conducted a prospective, single-blind, randomized trial to observe the effect of the medications on preoperative arterial blood pressure recordings in patients presenting for ambulatory and same-day surgery. Six hundred forty-four patients presenting for ambulatory and same-day surgery were enrolled prospectively between 2006 and 2011 and randomly assigned to 2 groups based on continuation or discontinuation of ACEIs and ARBs. An intention-to-treat analysis was performed. The primary outcome was presence of hypertension (HTN) immediately before surgery. Secondary outcomes included surgical cancellations due to HTN, prolongation of hospitalization, adverse clinical events, and HTN in the postoperative period. Data for 526 patients were analyzed. There were 262 patients in the discontinuation group and 264 patients in the continuation group. Discontinuation of ACEIs and ARBs on the day of surgery was not associated with increased prevalence of preoperative HTN (P = 0.775). The upper bound of a 95% confidence interval for the difference in prevalence of Stage 1 and 2 HTN between study arms indicates that discontinuation of study medication is unlikely to be associated with an increase in Stage 1 HTN of >4.8 percentage points and in Stage 2 HTN of no >5.8 percentage points. Discontinuation was not associated with an increase in postoperative HTN, with prolongation of hospitalization or with adverse clinical events. Discontinuing ACEIs and ARBs in patients on the day of surgery did not result in a

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

    Institute of Scientific and Technical Information of China (English)

    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

  6. Cost-utility of angiotensin-converting enzyme inhibitor-based treatment compared with thiazide diuretic-based treatment for hypertension in elderly Australians considering diabetes as comorbidity.

    Science.gov (United States)

    Chowdhury, Enayet K; Ademi, Zanfina; Moss, John R; Wing, Lindon M H; Reid, Christopher M

    2015-03-01

    The objective of this study was to examine the cost-effectiveness of angiotensin-converting enzyme inhibitor (ACEI)-based treatment compared with thiazide diuretic-based treatment for hypertension in elderly Australians considering diabetes as an outcome along with cardiovascular outcomes from the Australian government's perspective.We used a cost-utility analysis to estimate the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained. Data on cardiovascular events and new onset of diabetes were used from the Second Australian National Blood Pressure Study, a randomized clinical trial comparing diuretic-based (hydrochlorothiazide) versus ACEI-based (enalapril) treatment in 6083 elderly (age ≥65 years) hypertensive patients over a median 4.1-year period. For this economic analysis, the total study population was stratified into 2 groups. Group A was restricted to participants diabetes free at baseline (n = 5642); group B was restricted to participants with preexisting diabetes mellitus (type 1 or type 2) at baseline (n = 441). Data on utility scores for different events were used from available published literatures; whereas, treatment and adverse event management costs were calculated from direct health care costs available from Australian government reimbursement data. Costs and QALYs were discounted at 5% per annum. One-way and probabilistic sensitivity analyses were performed to assess the uncertainty around utilities and cost data.After a treatment period of 5 years, for group A, the ICER was Australian dollars (AUD) 27,698 (&OV0556; 18,004; AUD 1-&OV0556; 0.65) per QALY gained comparing ACEI-based treatment with diuretic-based treatment (sensitive to the utility value for new-onset diabetes). In group B, ACEI-based treatment was a dominant strategy (both more effective and cost-saving). On probabilistic sensitivity analysis, the ICERs per QALY gained were always below AUD 50,000 for group B; whereas for group A, the

  7. Meta-Analysis of Randomized Trials on the Efficacy and Safety of Angiotensin-Converting Enzyme Inhibitors in Patients ≥65 Years of Age.

    Science.gov (United States)

    Bavishi, Chirag; Ahmed, Mohammed; Trivedi, Vrinda; Khan, Abdur Rahman; Gongora, Carlos; Bangalore, Sripal; Messerli, Franz H

    2016-11-01

    The comparative efficacy and safety of angiotensin-converting enzyme inhibitors (ACEIs) with other agents in patients ≥65 years of age with cardiovascular diseases or at-risk are unknown. Electronic databases were systematically searched to identify all randomized controlled trials that compared ACEIs with control (placebo or active) and reported long-term cardiovascular outcomes. We required the mean age of patients in the studies to be ≥65 years. Random-effects model was used to pool study results. Sixteen trials with 104,321 patients and a mean follow-up of 2.9 years were included. Compared with placebo, ACEIs significantly reduced all outcomes except stroke. Compared with active controls, ACEIs had similar effect on all-cause mortality (relative risk [RR] 0.99, 95% confidence interval [CI] 0.95 to 1.03), cardiovascular mortality (RR 0.99, 95% CI 0.93 to 1.04), heart failure (RR 0.97, 95% CI 0.91 to 1.03), myocardial infarction (RR 0.94, 95% CI 0.88 to 1.00), and stroke (RR 1.07, 95% CI 0.99 to 1.15). ACEIs were associated with an increased risk of angioedema (RR 2.79, 95% CI 1.05 to 7.42), whereas risk for hypotension and renal insufficiency was similar compared with active controls. Meta-regression analysis showed that the effect of ACEIs on outcomes remained consistent with age increasing ≥65 years. Sensitivity analysis excluding trials comparing ACEIs with angiotensin receptor blockers and heart failure trials yielded similar results, except for reduction in myocardial infarction. In conclusion, the efficacy of ACEIs was similar to active controls for mortality outcomes. Compared with placebo, there was evidence for reduction in cardiovascular outcomes; however, ACEIs failed to prevent stroke and increased the risk of angioedema, hypotension, and renal failure. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers in Patients Without Heart Failure? Insights From 254,301 Patients From Randomized Trials.

    Science.gov (United States)

    Bangalore, Sripal; Fakheri, Robert; Toklu, Bora; Ogedegbe, Gbenga; Weintraub, Howard; Messerli, Franz H

    2016-01-01

    To compare the efficacy and safety of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) in patients without heart failure. Meta-analysis of randomized trials identified using PubMed, Embase, and Cochrane Central Register of Controlled Trials searches from January 1, 1980, through April 13, 2015, of ACEis and ARBs compared with placebo or active controls and corroborated with head-to-head trials of ARBs vs ACEis. Outcomes were all-cause mortality, cardiovascular death, myocardial infarction (MI), angina, stroke, heart failure, revascularization, and new-onset diabetes. Our search yielded 106 randomized trials that enrolled 254,301 patients. Compared with placebo, ACEis but not ARBs reduced the outcomes of all-cause mortality (ACEis vs placebo: relative risk [RR], 0.89; 95% CI, 0.80-1.00; ARBs vs placebo: RR, 1.01; 95% CI, 0.96-1.06; Pinteraction=.04), cardiovascular death (RR, 0.83; 95% CI, 0.70-0.99 and RR, 1.02; 95% CI, 0.92-1.14; Pinteraction=.05), and MI (RR, 0.83; 95% CI, 0.78-0.90 and RR, 0.93; 95% CI, 0.85-1.03; Pinteraction=.06). The meta-regression analysis revealed that the difference between ACEis and ARBs compared with placebo was due to a higher placebo event rate in the ACEis trials (most of these trials were conducted a decade earlier than the ARB trials) for the outcome of all-cause mortality (P=.001), cardiovascular death (PACEis vs placebo and ARBs vs placebo (Pinteraction>.05). Head-to-head comparison trials of ARBs vs ACEis exhibited no difference in outcomes except for a lower risk of drug withdrawal due to adverse effects with ARBs (RR, 0.72; 95% CI, 0.65-0.81). In patients without heart failure, evidence from placebo-controlled trials (restricted to trials after 2000), active controlled trials, and head-to-head randomized trials all suggest ARBs to be as efficacious and safe as ACEis, with the added advantage of better tolerability. Copyright © 2016 Mayo Foundation for Medical Education and Research

  9. Prescriptions for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and monitoring of serum creatinine and potassium in patients with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Pei-Tzu Wang

    2012-09-01

    Full Text Available Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs are commonly used in patients with chronic kidney disease (CKD. We studied the status of ACEI/ARB prescriptions and serum creatinine (Scr and potassium monitoring in CKD patients. A retrospective observational study was conducted on patients who had at least two sets of Scr data at outpatient visit. Estimated glomerular filtration rate (eGFR based on the second Scr value was calculated using the Modification of Diet in Renal Disease four-variable equation. CKD was defined and staged according to the National Kidney Foundation Disease Outcomes Quality Initiative Guideline. Patients with diabetes and/or hypertension with an eGFR over 60 mL/min/1.73 m2 and without proteinuria were defined as the CKD-at-risk group. The percentages and factors associated with ACEI/ARB prescription and Scr and potassium monitoring were calculated and analyzed by logistic regression. Among the 5714 subjects included, ACEIs/ARBs were prescribed to over 50% of patients in the CKD-at-risk group and in CKD stages 1–5. After adjusting for age, sex, potassium level, eGFR, and co-morbidities, the odds ratios for prescriptions of ACEIs/ARBs were 1.66 [95% confidence interval (CI 1.44–1.91, p < 0.001 and 2.80 (95% CI 2.12–3.70, p < 0.001 in CKD stage 3, and stages 4 and 5, respectively, compared with the reference group (eGFR≥60 mL/min/1.73 m2. During the year of ACEI/ARB treatment, Scr was monitored in 91.6% of ACEI/ARB-treated patients, while potassium was monitored in only 38.1%. Renal function status was the independent factor for monitoring of Scr and potassium. In conclusion, prescription of ACEIs/ARBs was common in all stages of CKD. Most patients underwent Scr monitoring, but potassium monitoring was less frequent, and this should be improved in clinical practice.

  10. Angiotensin-converting enzyme inhibitors (ACEIs), not angiotensin receptor blockers (ARBs), are preferred and effective mode of therapy in high cardiovascular risk patients.

    Science.gov (United States)

    Vijan, Suresh G

    2009-03-01

    Blockade of the renin-angiotensin system (RAS) plays an important role in the prevention and correction of cardiovascular diseases. Agents that block the RAS such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are major in this league. There have been numerous clinical trials looking at the use of ACEIs and ARBs in hypertension, heart failure (HF), and other special population who remain at high risk for cardiovascular and cardiometabolic abnormalities. Overall, ACEIs are the first line agents, recommended for high cardiovascular risk patients and are supported suitably by worldwide therapeutic guidelines including class IA recommendation from American College of Cardiology (ACC)/American Heart Association. These recommendations are based on, large body of clinical results which overall supports ACEIs in reducing mortality, MI, stroke, and new-onset congestive heart failure, and their unique cardioprotective benefits in patients with diabetes, independent of coexistent atherosclerosis and concomitant nephropathy. Although, theoretically, ARBs offer improved blockade of the RAS system than ACEIs, their relative effectiveness in the treatment of HF and other comorbid cardiovascular conditions remains controversial as evident from clinical trial and meta-analysis results which shows that ARBs are not as effective in reducing mortality, rate of hospitalisation, prevention of nephropathic progression, etc. The results from the latest ONTARGET 'non-inferiority' trial has further elucidated the fact that ARBs are no better than ACEIs at reducing fatal and non-fatal cardiovascular events including MI and CV death. Although theoretically, combination of ACEIs and ARBs is an attractive therapeutic option as none of them block RAS completely, but it may also open the gate for supplementary collection of adverse events as has been evidenced in recent trials. Although, there are no data at present to precisely suggest the efficacy

  11. Serum angiotensin converting enzyme in pemphigus vulgaris

    Directory of Open Access Journals (Sweden)

    Reza M Robati

    2014-01-01

    Full Text Available Background: Pemphigus vulgaris is an autoimmune blistering skin disease with unknown etiology. Drugs such as angiotensin-converting enzyme (ACE inhibitors may contribute in the pathogenesis of pemphigus. Objective: We plan this essay to evaluate the serum ACE level in pemphigus vulgaris patients in comparison with healthy controls to recognize its possible role in disease pathogenesis or activity. Methods: This study was planned and performed in the dermatology clinics of Shahid Beheshti University of MedicalSciences′ Hospitals between July 2010 and June 2011. Patients with new onset of pemphigus vulgaris were enrolled in our study. Control subjects were frequency-matched to cases by sex and age. Serum ACE was determined by the spectrophotometric method. Results: Thirty-four patients with pemphigus vulgaris and 35 healthy individuals were recruited in the study. No statistical significant difference was detected in the mean level of serum ACE of the two groups (t-test, P = 0.11. The mean ACE level was significantly lower in male patients compared with male controls (P = 0.04. Moreover, a significant higher serum ACE level of patients with cutaneous involvement was observed compared to patients with mucosal involvement (P = 0.02. Conclusions: Despite lack of any significant difference of serum ACE level between pemphigus and control group, the serum ACE level was considerably lower in male pemphigus vulgaris patients compared with male controls. Therefore, ACE might have some association with pemphigus vulgaris especially in male patients; however, further studies are required to confirm this association.

  12. Angiotensin converting enzyme inhibitors effect on arterial stiffness and wave reflections: a meta-analysis and meta-regression of randomised controlled trials.

    Science.gov (United States)

    Shahin, Yousef; Khan, Junaid Alam; Chetter, Ian

    2012-03-01

    Several studies have assessed the effect of angiotensin converting enzyme inhibitors (ACEIs) on arterial stiffness and wave reflections as measured by pulse wave velocity (PWV) and augmentation index (AIx), respectively. We conducted a meta-analysis to investigate this effect in comparison to placebo and to other antihypertensive agents. Additionally, we investigated this effect when ACEIs are combined with other antihypertensive agents and in comparison to a combination of antihypertensive agents. MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception to May 2011 on randomised controlled trials (RCTs) which assessed the effect of ACEIs on arterial stiffness vs. placebo or no treatment and ACEIs vs. angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), β-blockers and diuretics. RCTs which assessed the effect of ACEIs combined with other antihypertensives or compared ACEIs with a combination of antihypertensives were also sought. Data from included RCTs were pooled with use of fixed and random effects meta-analysis of the weighted mean change differences between the comparator groups. Heterogeneity across studies was assessed with the I(2) statistic. In 5 trials including 469 patients, treatment with ACEIs (n=227) vs. placebo (n=216) significantly reduced PWV (pooled mean change difference -1.69, 95% C.I. -2.05, -1.33, pACEIs (n=178) insignificantly reduced PWV when compared with other antihypertensives (ARBs, CCBs, β-blockers, diuretics and a combination of ACEI and ARB) (n=220) (pooled mean change difference -0.19, 95% C.I. -0.59, 0.21, p=0.36, I(2)=0%). ACEI effect on AIx in comparison to placebo was assessed in 7 trials. Treatment with ACEIs significantly reduced AIx (pooled mean change difference -3.79, 95% C.I. -5.96, -1.63, p=0.0006) with significant heterogeneity. In 7 trials, treatment with ACEIs significantly reduced AIx when compared with other antihypertensives (pooled mean change

  13. Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study

    Science.gov (United States)

    Lapi, Francesco; Azoulay, Laurent; Yin, Hui; Nessim, Sharon J

    2013-01-01

    Objectives To assess whether a double therapy combination consisting of diuretics, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers with addition of non-steroidal anti-inflammatory drugs (NSAIDs) and the triple therapy combination of two of the aforementioned antihypertensive drugs to which NSAIDs are added are associated with an increased risk of acute kidney injury. Design Retrospective cohort study using nested case-control analysis. Setting General practices contributing data to the UK Clinical Practice Research Datalink linked to the Hospital Episodes Statistics database. Participants A cohort of 487 372 users of antihypertensive drugs. Main outcome measures Rate ratios with 95% confidence intervals of acute kidney injury associated with current use of double and triple therapy combinations of antihypertensive drugs with NSAIDs. Results During a mean follow-up of 5.9 (SD 3.4) years, 2215 cases of acute kidney injury were identified (incidence rate 7/10 000 person years). Overall, current use of a double therapy combination containing either diuretics or angiotensin converting enzyme inhibitors or angiotensin receptor blockers with NSAIDs was not associated with an increased rate of acute kidney injury. In contrast, current use of a triple therapy combination was associated with an increased rate of acute kidney injury (rate ratio 1.31, 95% confidence interval 1.12 to 1.53). In secondary analyses, the highest risk was observed in the first 30 days of use (rate ratio 1.82, 1.35 to 2.46). Conclusions A triple therapy combination consisting of diuretics with angiotensin converting enzyme inhibitors or angiotensin receptor blockers and NSAIDs was associated with an increased risk of acute kidney injury. The risk was greatest at the start of treatment. Although antihypertensive drugs have cardiovascular benefits, vigilance may be warranted when they are used concurrently with NSAIDs. PMID:23299844

  14. Imbalance between pulmonary angiotensin-converting enzyme and angiotensin-converting enzyme 2 activity in acute respiratory distress syndrome

    NARCIS (Netherlands)

    Wosten-van Asperen, Roelie M.; Bos, Albert; Bem, Reinout A.; Dierdorp, Barbara S.; Dekker, Tamara; van Goor, Harry; Kamilic, Jelena; van der Loos, Chris M.; van den Berg, Elske; Bruijn, Martijn; van Woensel, Job B.; Lutter, Rene

    2013-01-01

    Objective: Angiotensin-converting enzyme and its effector peptide angiotensin II have been implicated in the pathogenesis of acute respiratory distress syndrome. Recently, angiotensin-converting enzyme 2 was identified as the counter-regulatory enzyme of angiotensin-converting enzyme that converts

  15. Imbalance between pulmonary angiotensin-converting enzyme and angiotensin-converting enzyme 2 activity in acute respiratory distress syndrome

    NARCIS (Netherlands)

    Wosten-van Asperen, Roelie M.; Bos, Albert; Bem, Reinout A.; Dierdorp, Barbara S.; Dekker, Tamara; van Goor, Harry; Kamilic, Jelena; van der Loos, Chris M.; van den Berg, Elske; Bruijn, Martijn; van Woensel, Job B.; Lutter, Rene

    2013-01-01

    Objective: Angiotensin-converting enzyme and its effector peptide angiotensin II have been implicated in the pathogenesis of acute respiratory distress syndrome. Recently, angiotensin-converting enzyme 2 was identified as the counter-regulatory enzyme of angiotensin-converting enzyme that converts a

  16. Economic evaluations of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in type 2 diabetic nephropathy: a systematic review.

    Science.gov (United States)

    Huang, Yunyu; Zhou, Qiyun; Haaijer-Ruskamp, Flora M; Postma, Maarten J

    2014-01-15

    Structured comparison of pharmacoeconomic analyses for ACEIs and ARBs in patients with type 2 diabetic nephropathy is still lacking. This review aims to systematically review the cost-effectiveness of both ACEIs and ARBs in type 2 diabetic patients with nephropathy. A systematic literature search was performed in MEDLINE and EMBASE for the period from November 1, 1999 to Oct 31, 2011. Two reviewers independently assessed the quality of the articles included and extracted data. All cost-effectiveness results were converted to 2011 Euros. Up to October 2011, 434 articles were identified. After full-text checking and quality assessment, 30 articles were finally included in this review involving 39 study settings. All 6 ACEIs studies were literature-based evaluations which synthesized data from different sources. Other 33 studies were directed at ARBs and were designed based on specific trials. The Markov model was the most common decision analytic method used in the evaluations. From the cost-effectiveness results, 37 out of 39 studies indicated either ACEIs or ARBs were cost-saving comparing with placebo/conventional treatment, such as amlodipine. A lack of evidence was assessed for valid direct comparison of cost-effectiveness between ACEIs and ARBs. There is a lack of direct comparisons of ACEIs and ARBs in existing economic evaluations. Considering the current evidence, both ACEIs and ARBs are likely cost-saving comparing with conventional therapy, excluding such RAAS inhibitors.

  17. Effects of Angiotensin-Converting Enzyme Inhibitor Derived from Tropaeolum majus L. in Rat Preimplantation Embryos: Evidence for the Dehydroepiandrosterone and Estradiol Role

    Directory of Open Access Journals (Sweden)

    Emerson Luiz Botelho Lourenço

    2014-01-01

    Full Text Available Although several studies have shown the inhibitory effects of Tropaeolum majus extracts (HETM on angiotensin-converting enzyme (ACE activity, no studies have been carried out during the beginning of pregnancy, when humoral and hormonal imbalance may affect zygote and early embryo transport. This study investigates whether HETM can affect embryonic development when administered during the one-cell-blastocyst period. Pregnant Wistar rats received orally the HETM (3, 30, and 300 mg/kg/day from the 1st to the 7th gestational day. Rats were killed on the 8th day of pregnancy and the following parameters were evaluated: clinical symptoms of toxicity (including organ weights, number of corpora lutea, implants per group, preimplantation losses ratio, and the serum levels of dehydroepiandrosterone (DHEA, estradiol, and progesterone. No clinical symptoms of maternal toxicity were evidenced. On the 8th day of pregnancy, the levels of DHEA and estradiol were increased and significant preimplantation losses were observed at all doses used. The present study reveals that the HETM can raise levels of DHEA and estradiol and induce difficulty in the embryo implantation in the early stages of pregnancy. The data contributes significantly to the safety aspects of using this natural product when trying to get pregnant or during pregnancy.

  18. 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

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    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

  19. Angiotensin converting enzyme 2 and atherosclerosis.

    Science.gov (United States)

    Wang, Yutang; Tikellis, Chris; Thomas, Merlin C; Golledge, Jonathan

    2013-01-01

    Angiotensin converting enzyme 2 (ACE2) is a homolog of angiotensin converting enzyme (ACE) which generates angiotensin II from angiotensin I. ACE, its product angiotensin II and the downstream angiotensin type I receptor are important components of the renin-angiotensin system (RAS). Angiotensin II, the most important component of the RAS, promotes the development of atherosclerosis. The identification of ACE2 in 2000 opened a new chapter of research on the regulation of the RAS. ACE2 degrades pro-atherosclerotic angiotensin II and generates anti-atherosclerotic angiotensin 1-7. In this review, we explored the importance of ACE2 in protecting experimental animals from developing atherosclerosis and its involvement in human atherosclerosis. We also examined the published evidence assessing the importance of ACE2 in different cell types relevant to atherosclerosis and putative underlying cellular and molecular mechanisms linking ACE2 with protection from atherosclerosis. ACE2 shifts the balance from angiotensin II to angiotensin 1-7 inhibiting the progression of atherosclerosis in animal models.

  20. An open-label, randomized, controlled, 4-week comparative clinical trial of barnidipine hydrochloride, a calcium-channel blocker, and benazepril, an angiotensin-converting enzyme inhibitor, in Chinese patients with renal parenchymal hypertension.

    Science.gov (United States)

    Chen, X; Zheng, F; Chen, P; Tang, L; Wei, R; Yu, Y; Su, Y; Kikkawa, T; Yamamoto, M

    2006-01-01

    This study compared barnidipine, a calcium-channel blocker, and benazepril, an angiotensin-converting enzyme inhibitor, in 85 Chinese patients with renal parenchymal hypertension (diastolic blood pressure range 95 - 110 mmHg). Patients were randomly assigned to receive either 10 mg barnidipine or 10 mg benazepril orally daily for 4 weeks. In patients with diastolic blood pressure > 90 mmHg after 2 weeks of treatment, the dose of barnidipine or benazepril was increased by 5 or 10 mg, respectively. Both the barnidipine-treated group (n = 43) and the benazepril-treated group (n = 42) showed significant mean reductions from baseline in sitting systolic and diastolic blood pressures. The decrease in diastolic blood pressure with benazepril was significantly greater than with barnidipine treatment. Sitting heart rate was not changed by either drug. There was no significant difference in adverse events between the two groups. Barnidipine is similar to benazepril for the treatment of renal parenchymal hypertension.

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

    DEFF Research Database (Denmark)

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

    2004-01-01

    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......% compared with placebo. CONCLUSION: In addition to the pronounced effect on mortality and morbidity in patients with symptomatic LVSD, ACE inhibitors have improving effect on functional capacity measured as exercise tolerance time....

  2. 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

    NARCIS (Netherlands)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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.

    Science.gov (United States)

    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.

  5. Analysis of Angiotensin-converting Enzyme Inhibitors by Mass Spectrometry%加合钠离子的血管紧张素转换酶抑制剂类化合物的质谱分析

    Institute of Scientific and Technical Information of China (English)

    朱培曦; 徐慧; 王峰; 李会林

    2011-01-01

    OBJECTIVE To establish a method for the identification of angiotensin-converting enzyme (ACE) inhibitors. METHODS Electrospray ionization tandem mass spectrometry (ESI-MS2) was employed and samples were introduced by a syringe pump. RESULTS Their fragmentation pathways were described and a unique rearrangement was observed for the eight compounds. CONCLUSION These characters can be used for future studies of ACE inhibitors.%目的 建立在加合钠离子条件下血管紧张素转换酶抑制剂类化合物质谱鉴定和分析的新方法.方法 电喷雾离子阱质谱,注射泵直接进样.结果 在加合钠离子的条件下,都出现了特殊的重排离子,通过对碎裂离子的分析,总结了这类化合物在加合钠离子的条件下的质谱碎裂特征.结论 采用解析加合钠离子的准分子离子碎裂途径的方法,有助于对这类化合物的结构推断.

  6. Endothelin-converting enzymes and related metalloproteases in Alzheimer's disease.

    Science.gov (United States)

    Pacheco-Quinto, Javier; Herdt, Aimee; Eckman, Christopher B; Eckman, Elizabeth A

    2013-01-01

    The efficient clearance of amyloid-β (Aβ) is essential to modulate levels of the peptide in the brain and to prevent it from accumulating in senile plaques, a hallmark of Alzheimer's disease (AD) pathology.We and others have shown that failure in Aβ catabolism can produce elevations in Aβ concentration similar to those observed in familial forms of AD. Based on the available evidence, it remains plausible that in late-onset AD, disturbances in the activity of Aβ degrading enzymes could induce Aβ accumulation, and that this increase could result in AD pathology. The following review presents a historical perspective of the parallel discovery of three vasopeptidases (neprilysin and endothelin-converting enzymes-1 and -2) as important Aβ degrading enzymes. The recognition of the role of these vasopeptidases in Aβ degradation, beyond bringing to light a possible explanation of how cardiovascular risk factors may influence AD risk, highlights a possible risk of the use of inhibitors of these enzymes for other clinical indications such as hypertension. We will discuss in detail the experiments conducted to assess the impact of vasopeptidase deficiency (through pharmacological inhibition or genetic mutation) on Aβ accumulation, as well as the cooperative effect of multiple Aβ degrading enzymes to regulate the concentration of the peptide at multiple sites, both intracellular and extracellular, throughout the brain.

  7. 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

    Directory of Open Access Journals (Sweden)

    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

  8. 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

    DEFF Research Database (Denmark)

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

    2003-01-01

    /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...... underwent exercise tolerance tests at 1, 3 and 12 months. The two treatment arms showed equal improvement in NYHA class both in the entire and exclusively symptomatic population over 4 years of follow-up (P=ns). ETT increased equally in both treatment arms at 1, 3, 12 months (P=ns). A mean of 12mg...

  9. Comparison of efficacy and side effects of combination therapy of angiotensin-converting enzyme inhibitor (benazepril) with calcium antagonist (either nifedipine or amlodipine) versus high-dose calcium antagonist monotherapy for systemic hypertension.

    Science.gov (United States)

    Messerli, F H; Oparil, S; Feng, Z

    2000-12-01

    The present 2 multicenter studies were designed to evaluate whether patients with essential hypertension derived equal benefits from use of combination therapy with a calcium antagonist and angiotensin-converting enzyme (ACE) inhibitor as from doubling the dose of the calcium antagonist. After a 2-week washout and a 2-week single-blind placebo run-in period, a total of 1,390 patients were treated with either nifedipine 30 mg (study 1) or amlodipine 5 mg (study 2) once daily for 4 weeks. The 1,079 patients whose diastolic blood pressure remained between 95 and 115 mm Hg were randomized to 8 weeks of double-blind therapy with amlodipine 5 mg/benazepril 10 mg, amlodipine 5 mg/ benazepril 20 mg, nifedipine 30 mg or nifedipine 60 mg (study 1), and amlodipine 5 mg/benazepril 10 mg, amlodipine 5 mg/benazepril 20 mg, amlodipine 5 mg or amlodipine 10 mg (study 2). Both doses of the calcium antagonist/ACE inhibitor combination therapy lowered diastolic pressure as much as the high dose and significantly better than the lower dose of calcium antagonist monotherapy (with either nifedipine or amlodipine). However, 15% of patients in the nifedipine high-dose monotherapy group and 24% in the amlodipine high-dose monotherapy group presented with some form of edema. In contrast, the incidence of edema was similar for patients treated with both combination therapy and low-dose calcium antagonists. Thus, combination therapy with a calcium antagonist and an ACE inhibitor provides blood pressure control equal to that of high-dose calcium antagonist monotherapy but with significantly fewer dose-dependent adverse experiences such as vasodilatory edema. Inc.

  10. Arterial hypertension treated with angiotensin converting enzyme inhibitors and glucocorticoids are independent risk factors associated with decreased glomerular filtration rate in systemic sclerosis.

    Science.gov (United States)

    Ostojic, Predrag; Stojanovski, Natasa

    2017-03-01

    The aim of this study was to estimate prevalence and severity of renal insufficiency in systemic sclerosis (SSc) and to assess risk factors associated with reduced glomerular filtration rate (GFR) in SSc patients. Seventy-three consecutive patients with SSc (67 women and 6 men), mean age 56.2 years, mean disease duration 6.7 years, were included in this cross-sectional study. GFR was measured by creatinine clearance (CCr) in all patients, as well as 24-h proteinuria. We assessed frequency and severity of renal insufficiency in our patients with SSc and estimated the association of renal insufficiency with age, disease duration, subtype of the disease, earlier diagnosed arterial hypertension, and medications for which we assumed to affect renal function-cytostatics, nonsteroidal anti-inflammatory drugs, glucocorticoids, ACE inhibitors, diuretics, and calcium channel blockers (CCB). Fifty-six out of 73 patients with SSc (76.7%) had reduced GFR (CCr lower than 90 ml/min), compared to 17/73 (23.3%) of patients with normal renal function. Mild renal insufficiency was noticed in 28/73 (38.4%), moderate in 21/73 (28.8%) and severe renal insufficiency in 5/73 (6.8%). End-stage renal disease (CCr arterial hypertension and treatment with glucocorticoids are independent risk factors for reduced GFR. On the other hand, age, disease duration, disease form, as well as antibodies (anticentromere antibodies-ACA and anti-topoisomerase I antibodies-ATA) were excluded as independent risk factors. Patients with SSc and arterial hypertension treated with CCB had significantly higher mean CCr than patients treated with diuretics (90.4 vs 53.5 ml/min, p = 0.03), or patients treated with ACE inhibitors (90.4 vs 41.7 ml/min, p = 0.001). Decreased GFR is common in SSc. Most of patients have mild or moderate renal insufficiency. Previously diagnosed arterial hypertension, especially when treated with ACE inhibitors or diuretics, and glucocorticoids are independent risk factors

  11. The Level of hs-CRP in Coronary Artery Ectasia and Its Response to Statin and Angiotensin-Converting Enzyme Inhibitor Treatment

    Directory of Open Access Journals (Sweden)

    Yilmaz Ozbay

    2007-01-01

    Materials and method. We measured serum hs-CRP level in 40 CAE (26 males, mean age: 56.32±9 years and 41 O-CAD (34 males, mean age: 57.19±10 years patients referred for elective coronary angiography at baseline and after 3-month statin and ACE inhibitor treatment. Results. Plasma hs-CRP levels were significantly higher in CAE group than O-CAD group at baseline (2.68±66 mg/L versus 1,64±64, resp., P<.0001. Plasma hs-CRP levels significantly decreased from baseline 3 months later in the CE (from 2.68±0.66 mg/L to 1.2±0.53 mg/L, P<.0001 as well as in the O-CAD group (from 1.64±0.64 mg/L to 1.01±0.56 mg/L, P<.001. Conclusion. We think that hs-CRP measurement may be a good prognostic value in CAE patients as in stenotic ones. Further placebo-controlled studies are needed to evaluate the clinical significance of this decrease in hs-CRP.

  12. Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin-Receptor Blockers (ARBs) in Patients at High Risk of Cardiovascular Events: A Meta-Analysis of 10 Randomised Placebo-Controlled Trials.

    Science.gov (United States)

    Ong, Hean Teik; Ong, Loke Meng; Ho, Jacqueline Judith

    2013-11-06

    Context. Whether angiotensin converting-enzyme inhibitors (ACEI) and angiotensin-receptor blockers (ARB) are useful in high risk patients without heart failure is unclear. We perform a meta-analysis of prospective randomized placebo-controlled ACEI or ARB trials studying patients with a combination of risk factors to assess treatment impact on all cause mortality, cardiovascular mortality, nonfatal myocardial infarction (MI) and stroke. Method. A PubMed search was made for placebo-controlled trials recruiting at least 1,200 high risk patients randomized to either ACEI or ARB, with follow-up of at least 2 years. Meta-analysis was performed using the RevMan 5 program and Mantel-Haenszel analysis was done with a fixed effects model. Results. Ten trials recruiting 77,633 patients were reviewed. All cause mortality was significantly reduced by ACEI (RR 0.89; P = 0.0008), but not by ARB treatment (RR 1.00; P = 0.89). Cardiovascular mortality and nonfatal MI were also reduced in the ACEI trials but not with ARB therapy. Stroke was significantly reduced in the ACEI trials (RR 0.75; P ACEI treatment reduced stroke, nonfatal MI, cardiovascular and total mortality in high risk patients, while ARB modestly reduced stroke with no effect on nonfatal MI, cardiovascular and total mortality.

  13. Impact of angiotensin converting enzyme inhibitors/angiotensin receptors blockers on mortality in acute heart failure patients with left ventricular systolic dysfunction in the Middle East: Observations from the Gulf Acute Heart Failure Registry (Gulf CARE).

    Science.gov (United States)

    Al-Zakwani, Ibrahim; Sulaiman, Kadhim; Al-Lawati, Jawad A; Alsheikh-Ali, Alawi A; Panduranga, Prashanth; AlHabib, Khalid F; Al Suwaidi, Jassim; Al-Mahmeed, Wael; AlFaleh, Hussam; Elasfar, Abdelfatah; Al-Motarreb, Ahmed; Ridha, Mustafa; Bulbanat, Bassam; Al-Jarallah, Mohammed; Bazargani, Nooshin; Asaad, Nidal; Amin, Haitham

    2017-08-17

    To evaluate the impact of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptors blockers (ARBs) on in-hospital, 3- and 12-month all-cause mortality in acute heart failure (AHF) patients with left ventricular systolic dysfunction in 7 countries of the Middle East. Data was analysed from 2,683 consecutive patients admitted with AHF and low ventricular ejection fraction (LVEF) (ACEIs were associated with lower risk of in-hospital mortality (adjusted odds ratio (aOR), 0.48; 95% confidence interval (CI): 0.25 to 0.94; p=0.031). At 3-month follow-up, both ACEIs (aOR= 0.64; 95% CI: 0.43 to 0.95; p=0.025) and ARBs (aOR=0.34; 95% CI: 0.18 to 0.62; pACEIs (aOR, 0.71; 95% CI: 0.53 to 0.96; p=0.027) and ARBs (aOR, 0.47; 95% CI: 0.31 to 0.71; pACEIs and ARBs treatments were associated with lower mortality risk during admission and up to 12-month of follow-up in Middle East AHF patients with left ventricular systolic dysfunction. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Angiotensin-converting enzyme inhibitors in preventing remodeling and development of heart failure after acute myocardial infarction: results of the German multicenter study of the effects of captopril on cardiopulmonary exercise parameters (ECCE).

    Science.gov (United States)

    Kleber, F X; Sabin, G V; Winter, U J; Reindl, I; Beil, S; Wenzel, M; Fischer, M; Doering, W

    1997-08-04

    Early action of angiotensin-converting enzyme (ACE) inhibitors after myocardial infarction (MI) has been shown in large scale clinical trials to reduce mortality over the first weeks. However, the mechanisms involved are yet unclear and several trials showed a tendency toward a small, albeit unexpected, rise in cardiogenic shock or mortality. Since cardiopulmonary exercise testing (CPX) has become a "gold standard" in assessing the severity of heart failure, we studied--after finishing a pilot trial--the effect of captopril versus placebo in 208 patients who were individually titrated (titrated dose, mean 46/69 mg/day after 7 days/4 weeks, respectively) in order to preserve their blood pressure in the acute phase of myocardial infarction; we followed the development of congestive heart failure (CHF) over 4 weeks by measuring oxygen consumption. After 4 weeks, overall oxygen consumption at the anaerobic threshold (VO2-AT; 13.7 vs 13.1), maximal oxygen consumption (VO2max 19.3 vs 18.9 mL/kg per min) and exercise duration (896 vs 839 sec) showed a nonsignificant difference in favor of the captopril group. The predefined, categorized, combined endpoint of severe heart failure or death (heart failure necessitating ACE inhibition, VO2max 10 patients per 100 treated gained major benefits from this therapy.

  15. 血管紧张素转化酶抑制剂在慢性心力衰竭中的应用%Angiotensin-converting enzyme inhibitors in the treatment of chronic heart failure

    Institute of Scientific and Technical Information of China (English)

    李新立; 周芳

    2011-01-01

    The target of chronic heart failure (CHF) treatment is not only to improve the symptoms and life quality, but also to delay or prevent from the myocardial reconstruction development in order to decrease the mortality and hospitalization rate. Drug therapy is still the major strategy for CHF. Angiotensin-converting enzyme inhibitors (ACEIs) are always the first-line drugs in the treatment of CHF. Recently, angiotensin II receptor blockers (ARBs) have been demonstrated to improve the prognosis of CHF, but there is no much superiority compared with ACEIs. This review discusses the clinical application of ACEIs for CHF.%慢性心力衰竭(CHF)的治疗目标不仅仅是改善症状、提高生活质量,更重要的是延缓和防止心室重构发展,降低CHF死亡率和住院率,目前临床药物治疗仍居主导地位.血管紧张素转化酶抑制剂(ACEI)一直是CHF治疗的一线药物,血管紧张素Ⅱ受体阻断剂(ARB)对CHF预后也有益,但与ACEI相比,其并无显著优势.本文综述ACEI在CHF治疗中的临床地位.

  16. Carbamazepine inhibits angiotensin I-converting enzyme, linking it to the pathogenesis of temporal lobe epilepsy

    Science.gov (United States)

    Almeida, S S; Naffah-Mazzacoratti, M G; Guimarães, P B; Wasinski, F; Pereira, F E G; Canzian, M; Centeno, R S; Carrete, H; Yacubian, E M; Carmona, A K; Vieira, R F F; Nakaie, C R; Sabatini, R A; Perosa, S R; Bacurau, R F P; Gouveia, T L F; Gallo, G; Würtele, M; Cavalheiro, E A; Silva, J A; Pesquero, J B; Araujo, R C

    2012-01-01

    We find that a common mutation that increases angiotensin I-converting enzyme activity occurs with higher frequency in male patients suffering from refractory temporal lobe epilepsy. However, in their brains, the activity of the enzyme is downregulated. As an explanation, we surprisingly find that carbamazepine, commonly used to treat epilepsy, is an inhibitor of the enzyme, thus providing a direct link between epilepsy and the renin–angiotensin and kallikrein–kinin systems. PMID:22832858

  17. Calmodulin interacts with angiotensin-converting enzyme-2 (ACE2) and inhibits shedding of its ectodomain.

    Science.gov (United States)

    Lambert, Daniel W; Clarke, Nicola E; Hooper, Nigel M; Turner, Anthony J

    2008-01-23

    Angiotensin-converting enzyme-2 (ACE2) is a regulatory protein of the renin-angiotensin system (RAS) and a receptor for the causative agent of severe-acute respiratory syndrome (SARS), the SARS-coronavirus. We have previously shown that ACE2 can be shed from the cell surface in response to phorbol esters by a process involving TNF-alpha converting enzyme (TACE; ADAM17). In this study, we demonstrate that inhibitors of calmodulin also stimulate shedding of the ACE2 ectodomain, a process at least partially mediated by a metalloproteinase. We also show that calmodulin associates with ACE2 and that this interaction is decreased by calmodulin inhibitors.

  18. The angiotensin converting enzyme inhibitor, captopril, prevents the hyperactivity and impulsivity of neurokinin-1 receptor gene 'knockout' mice: sex differences and implications for the treatment of attention deficit hyperactivity disorder.

    Science.gov (United States)

    Porter, Ashley J; Pillidge, Katharine; Grabowska, Ewelina M; Stanford, S Clare

    2015-04-01

    Mice lacking functional neurokinin-1 receptors (NK1R-/-) display behavioural abnormalities resembling attention deficit hyperactivity disorder (ADHD): locomotor hyperactivity, impulsivity and inattentiveness. The preferred ligand for NK1R, substance P, is metabolised by angiotensin converting enzyme (ACE), which forms part of the brain renin angiotensin system (BRAS). In view of evidence that the BRAS modulates locomotor activity and cognitive performance, we tested the effects of drugs that target the BRAS on these behaviours in NK1R-/- and wildtype mice. We first tested the effects of the ACE inhibitor, captopril, on locomotor activity. Because there are well-established sex differences in both ADHD and ACE activity, we compared the effects of captopril in both male and female mice. Locomotor hyperactivity was evident in male NK1R-/- mice, only, and this was abolished by treatment with captopril. By contrast, male wildtypes and females of both genotypes were unaffected by ACE inhibition. We then investigated the effects of angiotensin AT1 (losartan) and AT2 (PD 123319) receptor antagonists on the locomotor activity of male NK1R-/- and wildtype mice. Both antagonists increased the locomotor activity of NK1R-/- mice, but neither affected the wildtypes. Finally, we tested the effects of captopril on the performance of male NK1R-/- and wildtype mice in the 5-choice serial reaction-time task (5-CSRTT) and found that ACE inhibition prevented the impulsivity of NK1R-/- mice. These results indicate that certain behaviours, disrupted in ADHD, are influenced by an interaction between the BRAS and NK1R, and suggest that ACE inhibitors could provide a novel treatment for this disorder.

  19. The angiotensin converting enzyme inhibitor, captopril, prevents the hyperactivity and impulsivity of neurokinin-1 receptor gene ‘knockout’ mice: Sex differences and implications for the treatment of attention deficit hyperactivity disorder

    Science.gov (United States)

    Porter, Ashley J.; Pillidge, Katharine; Grabowska, Ewelina M.; Stanford, S. Clare

    2015-01-01

    Mice lacking functional neurokinin-1 receptors (NK1R−/−) display behavioural abnormalities resembling attention deficit hyperactivity disorder (ADHD): locomotor hyperactivity, impulsivity and inattentiveness. The preferred ligand for NK1R, substance P, is metabolised by angiotensin converting enzyme (ACE), which forms part of the brain renin angiotensin system (BRAS). In view of evidence that the BRAS modulates locomotor activity and cognitive performance, we tested the effects of drugs that target the BRAS on these behaviours in NK1R−/− and wildtype mice. We first tested the effects of the ACE inhibitor, captopril, on locomotor activity. Because there are well-established sex differences in both ADHD and ACE activity, we compared the effects of captopril in both male and female mice. Locomotor hyperactivity was evident in male NK1R−/− mice, only, and this was abolished by treatment with captopril. By contrast, male wildtypes and females of both genotypes were unaffected by ACE inhibition. We then investigated the effects of angiotensin AT1 (losartan) and AT2 (PD 123319) receptor antagonists on the locomotor activity of male NK1R−/− and wildtype mice. Both antagonists increased the locomotor activity of NK1R−/− mice, but neither affected the wildtypes. Finally, we tested the effects of captopril on the performance of male NK1R−/− and wildtype mice in the 5-choice serial reaction-time task (5-CSRTT) and found that ACE inhibition prevented the impulsivity of NK1R−/− mice. These results indicate that certain behaviours, disrupted in ADHD, are influenced by an interaction between the BRAS and NK1R, and suggest that ACE inhibitors could provide a novel treatment for this disorder. PMID:25703442

  20. Angiotensin converting enzyme genotype in cardiovascular disease

    Energy Technology Data Exchange (ETDEWEB)

    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.

  1. 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

    Institute of Scientific and Technical Information of China (English)

    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.

  2. Isolation of human liver angiotensin-converting enzyme by chromatofocusing.

    Science.gov (United States)

    Sakharov IYu; Danilov, S M; Sukhova, N V

    1987-10-01

    Angiotensin-converting enzyme (EC 3.4.15.1) has been isolated from human liver by chromatofocusing. The isolation procedure permitted us to obtain a 9000-fold purified enzyme with a 22% yield. Specific activity of the angiotensin-converting enzyme was 10 units/mg of protein. The molecular mass of enzyme determined by polyacrylamide gel electrophoresis under denaturing conditions was 150,000. The isoelectric point (4.2-4.3) was also determined by chromatofocusing. The Km values of the enzyme for hippuryl-L-histidyl-L-leucine and N-benzyloxycarbonyl-L-phenylalanyl-L-histidyl-L-leucine are 5000 and 125 microM, respectively. The human liver angiotensin-converting enzyme is inhibited by bradykinin-potentiating factor SQ 20881 (IC50 = 18 nM).

  3. Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on all-cause mortality, cardiovascular deaths, and cardiovascular events in patients with diabetes mellitus: a meta-analysis.

    Science.gov (United States)

    Cheng, Jun; Zhang, Wen; Zhang, Xiaohui; Han, Fei; Li, Xiayu; He, Xuelin; Li, Qun; Chen, Jianghua

    2014-05-01

    Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) may have different effects on cardiovascular (CV) events in patients with diabetes mellitus (DM). To conduct a meta-analysis to separately evaluate the effects of ACEIs and ARBs on all-cause mortality, CV deaths, and major CV events in patients with DM. DATA SOURCES Data sources included MEDLINE (1966-2012), EMBASE (1988-2012), the Cochrane Central Register of Controlled Trials, conference proceedings, and article reference lists. We included randomized clinical trials reporting the effects of ACEI and ARB regimens for DM on all-cause mortality, CV deaths, and major CV events with an observation period of at least 12 months. Studies were excluded if they were crossover trials. Dichotomous outcome data from individual trials were analyzed using the risk ratio (RR) measure and its 95% CI with random-effects models. We estimated the difference between the estimates of the subgroups according to tests for interaction. We performed meta-regression analyses to identify sources of heterogeneity. Primary end points were all-cause mortality and death from CV causes. Secondary end points were the effects of ACEIs and ARBs on major CV events. Twenty-three of 35 identified trials compared ACEIs with placebo or active drugs (32,827 patients) and 13 compared ARBs with no therapy (controls) (23,867 patients). When compared with controls (placebo/active treatment), ACEIs significantly reduced the risk of all-cause mortality by 13% (RR, 0.87; 95% CI, 0.78-0.98), CV deaths by 17% (0.83; 0.70-0.99), and major CV events by 14% (0.86; 0.77-0.95), including myocardial infarction by 21% (0.79; 0.65-0.95) and heart failure by 19% (0.81; 0.71-0.93). Treatment with ARBs did not significantly affect all-cause mortality (RR, 0.94; 95% CI, 0.82-1.08), CV death rate (1.21; 0.81-1.80), and major CV events (0.94; 0.85-1.01) with the exception of heart failure (0.70; 0.59-0.82). Both ACEIs and ARBs were

  4. Angiotensin receptor blockers (ARB) outperform angiotensin-converting enzyme (ACE) inhibitors on ischemic stroke prevention in patients with hypertension and diabetes - A real-world population study in Taiwan.

    Science.gov (United States)

    Pai, Pei-Ying; Muo, Chih-Hsin; Sung, Fung-Chang; Ho, Hung-Chi; Lee, Yuan-Teh

    2016-07-15

    Combination therapy with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) has been stressed for its comprehensive blocking of the renin-angiotensin-aldosterone system, but the evidence for their respective safety and efficacy, in particular with stroke prevention, is still insufficient in population-based follow-up studies in the real world. Using Taiwan's National Health Insurance claims data, we identified 5445 subjects aged 18years and older who had newly diagnosed hypertension in 1997-2010, from them diagnosed type 2 diabetes later. Among them, 2161 patients took ACEI, 1703 patients took ARB, 165 patients took both ACEI and ARB, and 1416 patients had neither. During the follow-up period, the stroke incidence density was the lowest (23.02 per 1000person-years) in ARB group, followed by the group with neither medication, the ACEI group, and ARB/ACEI combination group (24.06, 30.23, and 37.86 per 1000person-years, respectively). Compared with patients taking neither medication, the adjusted hazard ratios (HRs) were 1.27 (95% CI 1.02-1.58) for ACEI group, 0.95 (95% CI 0.74-1.22) for ARB group, and 1.56 (95% CI 0.99-2.47) for ARB/ACEI combined group. Greater reduction in risk of stroke was observed in patients with high dose ARB (adjusted HR=0·42, 95% CI 0·24-0·75). Our findings support the practice that ARBs could be used, from the perspective of stroke prevention, as a first-line antihypertensive drug for patients with both hypertension and diabetes. The group with ARB regimen reduces 26% of stroke in contrast to the group with ACEI regimen. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. 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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. Do Angiotensin-Converting Enzyme Inhibitors Reduce the Risk of Symptomatic Radiation Pneumonitis in Patients with Non-small Cell Lung Cancer after Definitive Radiotherapy? Analysis of a Single-Institution Database

    Science.gov (United States)

    Wang, Hongmei; Liao, Zhongxing; Zhuang, Yan; Xu, Ting; Nguyen, Quynh-Nhu; Levy, Lawrence B.; O'eilly, Michael S.; Gold, Kathryn A.; Gomez, Daniel R.

    2014-01-01

    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). Patients and Methods We retrospectively identified patients who received definitive radiotherapy for stage I–III NSCLC in 2004–2010 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 the Common Terminology Criteria for Adverse Events v3.0. A Cox proportional hazard model was used to assess potential associations between ACEI use and risk of symptomatic RP. Results Of the 413 patients analyzed, 65 were using ACEIs during RT. In univariate analysis, the rate of grade ⩾2 RP seemed lower in ACEI users than in nonusers (34% vs 46%), but this apparent difference was not statistically significant (P=0.06). In multivariate analysis of all patients, ACEI use was not associated with the risk of symptomatic RP (hazard ratio [HR]=0.66, P=0.07) 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 grade ≥2 RP among patients who received a low (⩽;20 Gy) MLD (PACEIs during RT for NSCLC was not statistically significant on univariate or multivariate analyses, though certain subgroups may benefit from use (i.e., male patients and those with 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. PMID:24161424

  7. Secular Trends in Prescription Patterns of Single-Pill Combinations of an Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Plus a Thiazide Diuretic for Hypertensive Patients in Taiwan

    Science.gov (United States)

    Hsu, Chih-Neng; Wang, Tzung-Dau

    2013-01-01

    Background Poor adherence to recommended drug regimens is one of the fundamental issues behind suboptimal control rates of hypertension worldwide. Single-pill combinations (SPCs) improve patient adherence, decrease cost, and are increasingly prescribed in the Western societies. We conducted this study to elucidate the prescription patterns and the secular trends of SPCs in Taiwan. Methods We retrospectively reviewed the reimbursement database of Taiwan’s National Health Insurance from 2002 to 2007. Among the one million-person random samples, information from those coded with ICD-9 401-405 and antihypertensive prescriptions was obtained. Results From 2002 to 2007, there had been amore than 7.5-fold increase in annual prescription frequency of SPCs of an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) plus a thiazide diuretic (from 1.1% to 8.5%, p ACEIs or ARBs and diuretics, the relative proportion of SPC use, in contrast to free combinations, increased markedly (from 10.8% to 54.2%, p = 0.005). Incorporating patient antihypertensive treatment prior to SPCs prescription,we categorized the SPC prescription patterns into 3 groups: naïve, switch, and add-on. The increase in patients taking SPCs came mostly from the naïve SPC prescription group (from 2.3% in 2002 to 28.8% in 2007 among all patients treated with ACEIs or ARBs and thiazide diuretics, p = 0.003). Compared to both naïve and add-on SPC users, patients in the switch group had a greater pill burden and more comorbidities, whichmight drive physicians to switch from free combinations to SPCs. Conclusions Single-pill combinations are well-accepted and increasingly prescribed in Taiwan, particularly in drug-naïve hypertensive patients. This finding might indicate an aggressive attitude towards early hypertension control among physicians in Taiwan. PMID:27122684

  8. Angiotensin-converting enzyme inhibition or angiotensin receptor blockade in hypertensive diabetics?

    NARCIS (Netherlands)

    Laverman, G; Ruggenenti, P; Remuzzi, G

    2003-01-01

    Hypertension increases the renal and cardiovascular risks in diabetic patients. The beneficial effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on renal and cardiovascular outcomes are discussed in this paper, with a particular focus on their optimal use in the

  9. Renal-selective delivery and angiotensin-converting enzyme inhibition by subcutaneously administered captopril-lysozyme

    NARCIS (Netherlands)

    Prakash, Jai; van Loenen - Weemaes, Anne-miek; Haas, M; Proost, Hans; Meijer, D.K F; Moolenaar, Frits; Poelstra, Klaas; Kok, R.J

    In previous studies, we have demonstrated that the low molecular weight protein lysozyme can be used as a renal-selective drug carrier for delivery of the angiotensin-converting enzyme ( ACE) inhibitor captopril. Typically, such macromolecular drug-targeting preparations are administered

  10. [Percutaneous angioplasty of the left renal artery in a patient with acute infarction of the left kidney with persistent occlusion of the right renal artery treated with angiotensin converting enzyme inhibitor].

    Science.gov (United States)

    Latacz, Paweł; Rudnik, Andrzej; Gutowska, Aleksandra; Zając, Mariola; Kondys, Marek; Ludyga, Tomasz; Kazibudzki, Marek; Cierpka, Lech

    2011-01-01

    A case of a 67 year-old woman with acute renal syndrome during treatment of angiotensin converting enzyme is presented. In angiography was affirmed acute occlusion left renal artery (LRA) with chronic occlusion right renal artery. Percutaneous angioplasty with implantation stent of the LRA were performed with optimal effect. In this article, the clinical management of patients with angiographically documented acute occlusion renal artery is discussed.

  11. Angiotensin Converting Enzyme Regulates Cell Proliferation and Migration

    Science.gov (United States)

    Carvalho, Clarissa Coelho; Florentino, Rodrigo Machado; França, Andressa; Matias, Eveline; Guimarães, Paola Bianchi; Batista, Carolina; Freire, Valder; Carmona, Adriana Karaoglanovic; Pesquero, João Bosco; de Paula, Ana Maria; Foureaux, Giselle; Leite, Maria de Fatima

    2016-01-01

    Background The angiotensin-I converting enzyme (ACE) plays a central role in the renin-angiotensin system, acting by converting the hormone angiotensin-I to the active peptide angiotensin-II (Ang-II). More recently, ACE was shown to act as a receptor for Ang-II, and its expression level was demonstrated to be higher in melanoma cells compared to their normal counterparts. However, the function that ACE plays as an Ang-II receptor in melanoma cells has not been defined yet. Aim Therefore, our aim was to examine the role of ACE in tumor cell proliferation and migration. Results We found that upon binding to ACE, Ang-II internalizes with a faster onset compared to the binding of Ang-II to its classical AT1 receptor. We also found that the complex Ang-II/ACE translocates to the nucleus, through a clathrin-mediated process, triggering a transient nuclear Ca2+ signal. In silico studies revealed a possible interaction site between ACE and phospholipase C (PLC), and experimental results in CHO cells, demonstrated that the β3 isoform of PLC is the one involved in the Ca2+ signals induced by Ang-II/ACE interaction. Further studies in melanoma cells (TM-5) showed that Ang-II induced cell proliferation through ACE activation, an event that could be inhibited either by ACE inhibitor (Lisinopril) or by the silencing of ACE. In addition, we found that stimulation of ACE by Ang-II caused the melanoma cells to migrate, at least in part due to decreased vinculin expression, a focal adhesion structural protein. Conclusion ACE activation regulates melanoma cell proliferation and migration. PMID:27992423

  12. Possible identity of IL-8 converting enzyme in human fibroblasts as a cysteine protease.

    Science.gov (United States)

    Ohashi, Kensaku; Sano, Emiko; Nakaki, Toshio; Naruto, Masanobu

    2003-04-01

    A converting activity was characterized in human diploid fibroblasts, which secrete 72IL-8 and 77IL-8 in treatment with IFN-beta and poly I: poly C. 77IL-8 was significantly converted to 72IL-8 by a partially purified fraction of the culture supernatant of human diploid fibroblasts. The converting activity, which was temperature-dependent and optimal at pH 6, was completely inhibited by cysteine protease inhibitors, antipain dihydrochloride and E-64, but not by other types of protease inhibitors. These data clearly show that human diploid fibroblasts are capable of processing IL-8 to produce a mature IL-8 and that the putative converting enzyme appears to be a cysteine protease.

  13. Modulation of cutaneous inflammation by angiotensin-converting enzyme.

    Science.gov (United States)

    Scholzen, Thomas E; Ständer, Sonja; Riemann, Helge; Brzoska, Thomas; Luger, Thomas A

    2003-04-01

    Cutaneous neurogenic inflammation is a complex biological response of the host immune system to noxious stimuli. Present evidence suggests that zinc metalloproteases may play an important role in the regulation of neurogenic inflammation by controlling the local availability of neuropeptides, such as substance P (SP), that are capable of initiating or amplifying cutaneous inflammation after release from sensory nerves. To address the hypothesis that the dipeptidyl carboxypeptidase angiotensin-converting enzyme (ACE) is capable of modulating skin inflammation, we have analyzed murine allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD) using wild-type C57BL/6J (ACE(+/+)) or genetically engineered mice with a heterozygous deletion of somatic ACE (ACE(+/-)). In 2,4-dinitro-1-fluorobenzene-sensitized ACE(+/-) mice, ACD was significantly augmented in comparison to ACE(+/+) controls as determined by the degree of ear swelling after exposure to hapten. Likewise, systemic treatment of ACE(+/+) mice with the ACE inhibitor captopril before sensitization or elicitation of ACD significantly augmented the ACD response. In contrast, local damage and neuropeptide depletion of sensory nerves following capsaicin, injection of a bradykinin B(2), or a SP receptor antagonist before sensitization significantly inhibited the augmented effector phase of ACD in mice with functionally absent ACE. However, in contrast to ACD, the response to the irritant croton oil was not significantly altered in ACE(+/-) compared with ACE(+/+) mice. Thus, ACE by degrading bradykinin and SP significantly controls cutaneous inflammatory responses to allergens but not to irritants, which may explain the frequently observed exacerbation of inflammatory skin disease in patients under medication with ACE inhibitors.

  14. Antihypertensive efficacy of angiotensin converting enzyme inhibition and aspirin counteraction.

    Science.gov (United States)

    Guazzi, M D; Campodonico, J; Celeste, F; Guazzi, M; Santambrogio, G; Rossi, M; Trabattoni, D; Alimento, M

    1998-01-01

    Blockade of bradykinin breakdown and enhancement of prostaglandin release probably participate in the antihypertensive activity of angiotensin converting enzyme (ACE) inhibitors. Cyclooxygenase blockers may attenuate the efficacy of ACE inhibitors by interfering with prostaglandin synthesis, and patients taking aspirin may not benefit from ACE inhibition. This study was designed to evaluate the incidence of the counteractive phenomenon and to define minimal aspirin dosage that causes an antagonistic effect. These were 26 patients with mild to moderate hypertension (group 1) and 26 patients with severe untreated primary hypertension (group 2). Enalapril (20 mg twice a day) was used as a single drug in group 1 and was added to the combination of long-acting nifedipine (30 mg/day) and atenolol (50 mg/day) in group 2. Aspirin was tested at doses of 100 and 300 mg/day, and an attenuation of more than 20% of the mean blood pressure decrease produced by enalapril was the criteria that defined antagonism. The 100 mg dose was ineffective. However, 300 mg aspirin had an antagonistic effect in 57% of patients in group 1 and 50% of patients in group 2: mean arterial pressure was lowered by 63% and 91% less, respectively. Results were independent of the drug administration order. In "responders," aspirin significantly attenuated the renin rise associated with ACE inhibition. These findings suggest that a number of ACE-inhibited patients are susceptible to 300 mg/day aspirin, regardless of hypertension severity. Antagonism may be mediated through prostaglandin inhibition according to predominance, in an individual patient, of prostaglandin activation (also as a renin secretory stimulus) or angiotensin blockade by enalapril.

  15. 血管紧张素转换酶抑制剂治疗阿尔茨海默病的效果%Effects of angiotensin converting enzyme inhibitors on Alzheimer' s disease

    Institute of Scientific and Technical Information of China (English)

    储佺兵; 苑瑞敏; 童玉翠; 陈广生; 许家佳; 张晗; 孙永安

    2012-01-01

    目的 观察血管紧张素转换酶抑制剂( ACEI)治疗阿尔茨海默病(AD)痴呆患者的精神行为症状、认知功能损害的效果.方法 52例AD痴呆患者口服盐酸卡托普利治疗12周,采用神经精神科问卷(NPI)评定患者的精神行为症状变化,采用简易智能状态检查量表评定患者的认知功能变化.结果 治疗12周后,除情感淡漠外,NPI各项因子得分显著下降(P<0.05),NPI总分下降81.47% (P<0.05);照顾者的苦恼程度也随着患者精神行为症状的改善而降低;治疗前后患者的认知功能无显著性差异(P>0.05).结论 盐酸卡托普利可以明显改善AD痴呆患者的精神行为症状,但对患者的认知功能损害无明显疗效.%Objective To observe the effects of hydrochloride captopril, one of angiotensin converting enzyme inhibitors (ACEIs), on behavioral and psychological symptoms and cognitive impairments of Alzheimer' s disease. Methods Fifty-two patients with Alzheimer' s disease were treated with captopril for 12 weeks. The neural psychiatric questionnaire (NPI) and the mini-mental state examination(MMSE) were used to evaluate the efficacy and cognitive changes. Results After treated for 12 weeks, the scores of each NPI factor were significantly decreased(P0.05). Conclusion Hydrochloride captopril could significantly reduce the psychological and behavioral symptoms without improvement in the cognitive impairments.

  16. Effects of Atorvastatin Dose and Concomitant Use of Angiotensin-Converting Enzyme Inhibitors on Renal Function Changes over Time in Patients with Stable Coronary Artery Disease: A Prospective Observational Study

    Directory of Open Access Journals (Sweden)

    Ewa Wieczorek-Surdacka

    2016-02-01

    Full Text Available Angiotensin-converting enzyme inhibitors (ACEI and statins are widely used in patients with coronary artery disease (CAD. Our aim was to compare changes in glomerular filtration rate (GFR over time in subjects with stable CAD according to atorvastatin dose and concomitant use of ACEI. We studied 78 men with stable CAD referred for an elective coronary angiography who attained the then-current guideline-recommended target level of low-density lipoproteins (LDL cholesterol below 2.5 mmol/L in a routine fasting lipid panel on admission and were receiving atorvastatin at a daily dose of 10–40 mg for ≥3 months preceding the index hospitalization. Due to an observational study design, atorvastatin dosage was not intentionally modified for other reasons. GFR was estimated during index hospitalization and at about one year after discharge from our center. Irrespective of ACEI use, a prevention of kidney function loss was observed only in those treated with the highest atorvastatin dose. In 38 subjects on ACEI, both of the higher atorvastatin doses were associated with increasing beneficial effects on GFR changes (mean ± SEM: −4.2 ± 2.4, 1.1 ± 1.6, 5.2 ± 2.4 mL/min per 1.73 m2 for the 10-mg, 20-mg and 40-mg atorvastatin group, respectively, p = 0.02 by ANOVA; Spearman’s rho = 0.50, p = 0.001 for trend. In sharp contrast, in 40 patients without ACEI, no significant trend effect was observed across increasing atorvastatin dosage (respective GFR changes: −1.3 ± 1.0, −4.7 ± 2.1, 4.8 ± 3.6 mL/min per 1.73 m2, p = 0.02 by ANOVA; rho = 0.08, p = 0.6 for trend. The results were substantially unchanged after adjustment for baseline GFR or time-dependent variations of LDL cholesterol. Thus, concomitant ACEI use appears to facilitate the ability of increasing atorvastatin doses to beneficially modulate time-dependent changes in GFR in men with stable CAD.

  17. Health outcomes and economic consequences of using angiotensin-converting enzyme inhibitors in comparison with angiotensin receptor blockers in the treatment of arterial hypertension in the contemporary Polish setting.

    Science.gov (United States)

    Wrona, Witold; Budka, Katarzyna; Filipiak, Krzysztof J; Niewada, Maciej; Wojtyniak, Bogdan; Zdrojewski, Tomasz

    2016-01-01

    Arterial hypertension (AH) represents a public health problem in Poland, firstly due to the huge, still growing population of patients (10.45 million patients based on NATPOL 2011 and PolSenior Surveys), and secondly because of the substantial cost of reimbursement from the National Health Fund (NHF). The most commonly used drugs in the treatment of AH include angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), the latter being associated with significantly higher unit reimbursement cost. Recent meta-analyses of randomised, controlled trials indicate that there is no medical reason to favour ARBs over ACEIs in AH treatment. To assess the clinical benefit of using ACEIs instead of ARBs and to calculate the potential savings for the payer and patients associated with changing the treatment paradigm to preferential use of ACEIs. The assessment of clinical consequences includes differences between ACEIs and ARBs in terms of average life expectancy and quality-adjusted life years (QALYs) gained. The impact of these drugs on general mortality was estimated based on the meta-analysis carried out by van Vark et al. in 2012. Patients' health-related quality of life was adjusted with Polish population utility norms derived for the EQ-5D-3L questionnaire and additionally for ACEI-induced cough-related utility decrease. Potential savings for the payer on a yearly basis were calculated for a hypothetical cohort of patients who are currently treated with ARBs and might be switched to ACEIs. The number of patients treated with ARBs and ACEIs was estimated based on NHF and IMS Health data. ACEIs were associated with a statistically significant 10% reduction in all-cause mortality, which results in extra life gained of 0.354 years (4.2 months) or an additional 0.201 QALY (2.4 months). Potential annual savings could amount to 112.0 million PLN (25.7 million EUR) and 10.5 million PLN (2.4 million EUR) for the public payer (NHF) and patients

  18. The impact of the 'Better Care Better Value' prescribing policy on the utilisation of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for treating hypertension in the UK primary care setting: longitudinal quasi-experimental design.

    Science.gov (United States)

    Baker, Amanj; Chen, Li-Chia; Elliott, Rachel A; Godman, Brian

    2015-09-10

    In April/2009, the UK National Health Service initiated four Better Care Better Value (BCBV) prescribing indicators, one of which encouraged the prescribing of cheaper angiotensin-converting enzyme inhibitors (ACEIs) instead of expensive angiotensin receptor blockers (ARBs), with 80 % ACEIs/20 % ARBs as a proposed, and achievable target. The policy was intended to save costs without affecting patient outcomes. However, little is known about the actual impact of the BCBV indicator on ACEIs/ARBs utilisation and cost-savings. Therefore, this study aimed to evaluate the impact of BCBV policy on ACEIs/ARBs utilisation and cost-savings, including exploration of regional variations of the policy's impact. This cross-sectional study used data from the UK Clinical Practice Research Datalink. Segmented time-series analysis was applied to monthly ACEIs prescription proportion, adjusted number of ACEIs/ARBs prescriptions and costs. Overall, the proportion of ACEIs prescription decreased during the study period from 71.2% in April/2006 to 70.7% in March/2012, with a small but a statistically significant pre-policy reduction in its monthly trend of 0.02% (p ACEIs prescription; however, it resulted in a statistically significant increase in the post-policy monthly trend of ACEIs prescription proportion of 0.013% (p ACEIs/ARBs prescriptions was increasing; however, their trends declined after the policy implementation. The policy affected neither total ACEIs/ARBs cost nor individual ACEIs or ARBs costs. ACEIs/ARBs utilisation was not affected by the BCBV policy. The small increase in post-policy ACEIs prescription proportion was not associated with any savings. This study represents a case study of a failed or ineffective policy and thus provides key learning lessons for other healthcare authorities. Given the existing opportunity of potential cost-savings from achieving the 80 % target, specific measures would be needed to enhance the policy implementation and uptake; however

  19. 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.

    Science.gov (United States)

    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.

  20. Clinical events in high-risk hypertensive patients randomly assigned to calcium channel blocker versus angiotensin-converting enzyme inhibitor in the antihypertensive and lipid-lowering treatment to prevent heart attack trial.

    Science.gov (United States)

    Leenen, Frans H H; Nwachuku, Chuke E; Black, Henry R; Cushman, William C; Davis, Barry R; Simpson, Lara M; Alderman, Michael H; Atlas, Steven A; Basile, Jan N; Cuyjet, Aloysius B; Dart, Richard; Felicetta, James V; Grimm, Richard H; Haywood, L Julian; Jafri, Syed Z A; Proschan, Michael A; Thadani, Udho; Whelton, Paul K; Wright, Jackson T

    2006-09-01

    The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) provides a unique opportunity to compare the long-term relative safety and efficacy of angiotensin-converting enzyme inhibitor and calcium channel blocker-initiated therapy in older hypertensive individuals. Patients were randomized to amlodipine (n=9048) or lisinopril (n=9054). The primary outcome was combined fatal coronary heart disease or nonfatal myocardial infarction, analyzed by intention-to-treat. Secondary outcomes included all-cause mortality, stroke, combined cardiovascular disease (CVD), end-stage renal disease (ESRD), cancer, and gastrointestinal bleeding. Mean follow-up was 4.9 years. Blood pressure control was similar in nonblacks, but not in blacks. No significant differences were found between treatment groups for the primary outcome, all-cause mortality, ESRD, or cancer. Stroke rates were higher on lisinopril in blacks (RR=1.51, 95% CI 1.22 to 1.86) but not in nonblacks (RR=1.07, 95% CI 0.89 to 1.28), and in women (RR=1.45, 95% CI 1.17 to 1.79), but not in men (RR=1.10, 95% CI 0.92 to 1.31). Rates of combined CVD were higher (RR=1.06, 95% CI 1.00 to 1.12) because of higher rates for strokes, peripheral arterial disease, and angina, which were partly offset by lower rates for heart failure (RR=0.87, 95% CI 0.78 to 0.96) on lisinopril compared with amlodipine. Gastrointestinal bleeds and angioedema were higher on lisinopril. Patients with and without baseline coronary heart disease showed similar outcome patterns. We conclude that in hypertensive patients, the risks for coronary events are similar, but for stroke, combined CVD, gastrointestinal bleeding, and angioedema are higher and for heart failure are lower for lisinopril-based compared with amlodipine-based therapy. Some, but not all, of these differences may be explained by less effective blood pressure control in the lisinopril arm.

  1. Angiotensin converting enzyme in the testis and epididymis of mammals.

    Science.gov (United States)

    Jaiswal, A; Joshi, P; Kumar, M V; Panda, J N; Singh, L N

    1984-01-01

    Angiotensin converting enzyme (ACE) activity has been reported in testis and epididymis of seven different animal species. Among all the species, the mouse testis and epididymis showed the highest converting enzyme activity followed by rat testis and epididymis. The lowest activity was detected in buffalo testis and rabbit epididymis. Most of the testicular enzyme was found concentrated in the 107,00 X g sediment while the epididymal enzyme was equally distributed between sediment and supernatant. ACE levels of different regions of the rat testis and epididymis was analyzed. The gradient of ACE was found increasing from caput to cauda. A major fraction of testicular and epididymal ACE activity was found in their respective fluid. ACE appeared only in mature rats, rabbits and mice testis and epididymis. Sexually stimulated rabbits showed significant ACE increase in the testis. In vitro characterization studies were conducted.

  2. [Familial hyperactivity of angiotensin-converting enzyme (ACE)

    NARCIS (Netherlands)

    Kramers, C.; Adema, G.J.; Korte, M.; Deinum, J.

    2003-01-01

    An extremely high level of serum angiotensin-converting enzyme (ACE) activity was found in eight individuals, women aged 31, 60, 42 and 67 years, and men aged 50, 47, 23 and 50 years. They had consulted a specialist due to a wide range of non-specific complaints or abnormalities (fatigue, dyspnoea,

  3. Identification of interleukin-8 converting enzyme as cathepsin L.

    Science.gov (United States)

    Ohashi, Kensaku; Naruto, Masanobu; Nakaki, Toshio; Sano, Emiko

    2003-06-26

    IL-8 is produced by various cells, and the NH(2)-terminal amino acid sequence of IL-8 displays heterogeneity among cell types. The mature form of IL-8 has 72 amino acids (72IL-8), while a precursor form (77IL-8) of IL-8 has five additional amino acids to the 72IL-8 NH(2)-terminal. However, it has been unclear how IL-8 is processed to yield the mature form. In this study, converting enzyme was purified as a single 31-kDa band on silver-stained polyacrylamide gel from 160 l of cultured fibroblast supernatant by sequential chromatography. NH(2)-terminal amino acid sequence analysis revealed a sequence, EAPRSVDWRE, which was identified as a partial sequence of cathepsin L. Polyclonal antibodies raised against cathepsin L recognized the purified converting enzyme on Western blot. Moreover, human hepatic cathepsin L cleaved 77IL-8 between Arg(5) and Ser(6), which is the same cleavage site as the putative converting enzyme, resulting in 72IL-8 formation. These data indicate that the converting enzyme of the partially purified fraction of the human fibroblast culture supernatant was cathepsin L. Furthermore, 72IL-8 was sevenfold more potent than 77IL-8 in a neutrophil chemotaxis assay. These results show that cathepsin L is secreted from human fibroblasts in response to external stimuli and plays an important role in IL-8 processing in inflammatory sites.

  4. Mitochondrial uncoupling proteins regulate angiotensin-converting enzyme expression

    DEFF Research Database (Denmark)

    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...

  5. Mitochondrial uncoupling proteins regulate angiotensin-converting enzyme expression

    DEFF Research Database (Denmark)

    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 inhibition after myocardial infarction: the Trandolapril Cardiac Evaluation Study

    DEFF Research Database (Denmark)

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

    1996-01-01

    To study the importance of giving an angiotensin-converting enzyme (ACE) inhibitor to patients with reduced systolic function after an infarction, the Trandodolapril Cardiac Evaluation study was designed to include the majority of patients with echocardiographic signs of left ventricular dysfunct......To study the importance of giving an angiotensin-converting enzyme (ACE) inhibitor to patients with reduced systolic function after an infarction, the Trandodolapril Cardiac Evaluation study was designed to include the majority of patients with echocardiographic signs of left ventricular...... beginning on day 3 to 7 after the infarction. The follow-up period was 2 to 4 years. Trandolapril reduced all-cause mortality, with a relative risk reduction associated with trandolapril treatment of 0.78 (p = 0.0013). Benefit was seen within 1 month of treatment. Trandolapril also reduced cardiovascular...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. Inhibition of interleukin 1β converting enzyme family proteases reduces ischemic and excitotoxic neuronal damage

    OpenAIRE

    Hara, Hideaki; Robert M. Friedlander; Gagliardini, Valeria; Ayata, Cenk; Fink, Klaus; Huang, Zhihong; Shimizu-Sasamata, Masao; Yuan, Junying; Moskowitz, Michael A

    1997-01-01

    The interleukin 1β converting enzyme (ICE) family plays a pivotal role in programmed cell death and has been implicated in stroke and neurodegenerative diseases. During reperfusion after filamentous middle cerebral artery occlusion, ICE-like cleavage products and tissue immunoreactive interleukin 1β (IL-1β) levels increased in ischemic mouse brain. Ischemic injury decreased after intracerebroventricular injections of ICE-like protease inhibitors, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylke...

  9. Enzyme-inhibitor mediated red cell labelling

    Energy Technology Data Exchange (ETDEWEB)

    Ackery, D.M.; Singh, J.; Wyeth, P. (Southampton Univ. (UK). Dept. of Chemistry)

    Red blood cells contain 90% of the body's enzyme carbonic anhydrase to which aromatic sulphonamide inhibitors bind tightly. P-iodo-benzene sulphonamide (PIBS) is a lipophilic inhibitor which would afford rapid cell labelling. Radioiodinated PIBS was prepared, in high yield, by radio ion exchange in the presence of ammonium sulphate. After intravenous injection of /sup 131/I-PIBS the radiolabel was found in the blood pool.

  10. Tumor necrosis factor alpha converting enzyme: an encouraging target for various inflammatory disorders.

    Science.gov (United States)

    Bahia, Malkeet S; Silakari, Om

    2010-05-01

    Tumor necrosis factor alpha is one of the most common pro-inflammatory cytokines responsible for various inflammatory disorders. It plays an important role in the origin and progression of rheumatoid arthritis and also in other autoimmune disease conditions. Some anti-tumor necrosis factor alpha antibodies like Enbrel, Humira and Remicade have been successfully used in these disease conditions as antagonists of tumor necrosis factor alpha. Inhibition of generation of active form of tumor necrosis factor alpha is a promising therapy for various inflammatory disorders. Therefore, the inhibition of an enzyme (tumor necrosis factor alpha converting enzyme), which is responsible for processing inactive form of tumor necrosis factor alpha into its active soluble form, is an encouraging target. Many tumor necrosis factor alpha converting enzyme inhibitors have been the candidates of clinical trials but none of them have reached in to the market because of their broad spectrum inhibitory activity for other matrix metalloproteases. Selectivity of tumor necrosis factor alpha converting enzyme inhibition over matrix metalloproteases is of utmost importance. If selectivity is achieved successfully, side-effects can be over-ruled and this approach may become a novel therapy for treatment of rheumatoid arthritis and other inflammatory disorders. This cytokine not only plays a pivotal role in inflammatory conditions but also in some cancerous conditions. Thus, successful targeting of tumor necrosis factor alpha converting enzyme may result in multifunctional therapy.

  11. Angiotensin I-Converting Enzyme Inhibitory Peptides of Chia (Salvia hispanica) Produced by Enzymatic Hydrolysis

    OpenAIRE

    Maira Rubi Segura Campos; Fanny Peralta González; Luis Chel Guerrero; David Betancur Ancona

    2013-01-01

    Synthetic angiotensin I-converting enzyme (ACE-I) inhibitors can have undesirable side effects, while natural inhibitors have no side effects and are potential nutraceuticals. A protein-rich fraction from chia (Salvia hispanica L.) seed was hydrolyzed with an Alcalase-Flavourzyme sequential system and the hydrolysate ultrafiltered through four molecular weight cut-off membranes (1 kDa, 3 kDa, 5 kDa, and 10 kDa). ACE-I inhibitory activity was quantified in the hydrolysate and ultrafiltered fra...

  12. Development of enzymes and enzyme systems by genetic engineering to convert biomass to sugars

    Science.gov (United States)

    TITLE Development of Enzymes and Enzyme Systems by Genetic Engineering to Convert Biomass to Sugars ABSTRACT Plant cellulosic material is one of the most viable renewable resources for the world’s fuel and chemical feedstock needs. Currently ethanol derived from corn starch is the most common li...

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

    LENUS (Irish Health Repository)

    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.

  14. Angiotensin-converting enzyme inhibition in myocardial infarction--Part 1: Clinical data.

    Science.gov (United States)

    Huckell, V F; Bernstein, V; Cairns, J A; Crowell, R; Dagenais, G R; Higginson, L A; Isserow, S; Laramée, P; Liu, P; McCans, J L; Orchard, R C; Prewitt, R; Quinn, B P; Samson, M; Turazza, F; Warnica, J W; Wielgosz, A

    1997-02-01

    There is an increasing body of clinical trial evidence to support the use of angiotensin-converting enzyme (ACE) inhibitors in the management of patients following myocardial infarction (MI). Enthusiasm for the use of ACE inhibitors in the acute phase of MI had previously been tempered by the adverse results of an early trial. However, exciting new information is available from several large, randomized studies that has not only quelled those initial concerns but also attests to the efficacy of using this class of medication in the first 24 h after an acute MI. A Canadian National Opinion Leader Symposium was held in November 1995 to review the results of the major ACE inhibitor clinical trials and to discuss key issues and controversies surrounding their use in acute MI. The focus of this paper, the first of two parts, is on the results of the major ACE inhibitor clinical trials.

  15. Applications of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in the treatment of chronic heart failure%血管紧张素转换酶抑制剂和血管紧张素受体拮抗剂在慢性心力衰竭治疗中的应用

    Institute of Scientific and Technical Information of China (English)

    居海宁; 卞金陵

    2011-01-01

    Heart failure is the ultimate cause of death in a variety of heart diseases. It has been discovered that the main strategy of slowing the progress of heart failure diseases is blocking the renin angiotensin aldosterone system (RAAS). Angiotensin converting enzyme inhibitors(ACEI) and angiotensin receptor blockers( ARB) are the most commonly used RAAS-blocking drugs. In this paper,the assessment of chronic heart failure and the applications of ACEI and ARB in the treatment of chronic heart failure are reviewed.%心力衰竭是多种心脏病的最终死亡原因,阻断肾素-血管紧张素-醛固酮系统(renin angiotensin aldosterone system,RAAS)是减慢心力衰竭病变进展的主要策略.血管紧张素转换酶抑制剂(angiotensin converting enzyme inhibitors,ACEI)和血管紧张素受体拮抗剂(angiotensin receptor blockers,ARB)是目前最常用的阻断RAAS的药物.本文对慢性心力衰竭评估,以及ACEI和ARB在慢性心力衰竭治疗中的应用进行综述.

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

    NARCIS (Netherlands)

    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

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

    NARCIS (Netherlands)

    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

  18. Targeting of captopril to the kidney reduces renal angiotensin-converting enzyme activity without affecting systemic blood pressure

    NARCIS (Netherlands)

    Kok, RJ; Haverdings, Rene; Grijpstra, F; Koiter, J.; Moolenaar, F; De Zeeuw, D; Meijer, DKF

    We have synthesized a prodrug of the angiotensin-converting enzyme (ACE) inhibitor captopril by coupling this drug covalently to the low molecular weight protein (LMWP) lysozyme. Such drug-LMWP conjugates can be used for renal drug delivery, since LMWPs accumulate specifically in the proximal

  19. Effects of angiotensin-converting enzyme inhibition in low-risk patients early after coronary artery bypass surgery

    NARCIS (Netherlands)

    Rouleau, Jean L.; Warnica, Wayne J.; Baillot, Richard; Block, Pierre J.; Chocron, Sidney; Johnstone, David; Myers, Martin G.; Calciu, Cristina-Dana; Dalle-Ave, Sonia; Martineau, Pierre; Mormont, Christine; van Gilst, Wiek H.

    2008-01-01

    Background-Early after coronary artery bypass surgery (CABG), activation of numerous neurohumoral and endogenous vasodilator systems occurs that could be influenced favorably by angiotensin-converting enzyme inhibitors. Methods and Results-The Ischemia Management with Accupril post -bypass Graft via

  20. 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

    Directory of Open Access Journals (Sweden)

    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

  1. Renal scintigraphy following angiotensin converting enzyme inhibition in the diagnosis of renovascular hypertension (captopril scintigraphy)

    Energy Technology Data Exchange (ETDEWEB)

    Sfakianakis, G.N. (Univ. of Miami School of Medicine, FL (USA))

    1989-09-01

    This article describes the pathophysiology and primary causes of renovascular hypertension (RVH). No historical or physical finding is specific in the diagnosis of RVH, although onset of hypertension before the age of 30 years may suggest the possible presence of RVH. The physiology of the kidney is described along with the biochemistry of angiotensin converting enzyme inhibitors. The main thrust of the article is nuclear medicine techniques useful in the diagnosis of this disease. Several diagnositic methods are described but captopril scintigraphy is presented as a method that may give more optimal results in the diagnosis of RVH.

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

    DEFF Research Database (Denmark)

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

    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....... In the conventional group, the fractional clearances of these three plasma proteins all increased. It is concluded that in progressive chronic nephropathy ACE-inhibitor treatment was associated with different adaptive tubular changes in the handling of sodium, water, and protein compared with conventional...

  3. Responses to converting-enzyme inhibition and hemorrhage in newborn lambs and adult sheep

    Energy Technology Data Exchange (ETDEWEB)

    Rose, J.C.; Block, S.M.; Flowe, K.; Morris, M.; South, S.; Sundberg, D.K.; Zimmerman, C.

    1987-02-01

    The authors compared the cardiovascular and hormonal responses to angiotensin converting enzyme inhibition and hemorrhage of 20% of blood volume in chronically instrumented unanesthetized newborn lambs and adult sheep. Administration of the nonsulfhydryl-containing converting-enzyme inhibitor enalapril reduced mean arterial pressure in the newborn but not in the adult animals. Blood pressure fell in both age groups after hemorrhage, and the hemorrhage-induced fall in blood pressure, integrated over the period of hypovolemia, was more pronounced when converting-enzyme inhibition was present in the lambs. This was not observed in the adults. Cardiac output fell following hemorrhage in both age groups, and the fall was greater when enalapril was present in the lambs, but this was not the case in the adults. Hemorrhage increased plasma renin activity in both groups, and enalapril augmented this increase. Plasma concentrations of vasopressin, measured by radioimmunoassay, and catecholamines measured by radio enzymatic assay, increased following hemorrhage within and between groups. Taken together these data suggest that the renin-angiotensin systems plays a more important role in the maintenance of cardiovascular homeostasis in newborn lambs than it does in adult sheep, and catecholamine and vasopressin responses to volume loss can occur in the presence of blockade of the renin-angiotensin system.

  4. Folding in solution of the C-catalytic protein fragment of angiotensin-converting enzyme.

    Science.gov (United States)

    Vamvakas, Sotirios-Spyridon M; Leondiadis, Leondios; Pairas, George; Manessi-Zoupa, Evy; Spyroulias, Georgios A; Cordopatis, Paul

    2009-08-01

    Angiotensin-converting enzyme (ACE) is a key molecule of the renin-angiotensin-aldosterone system which is responsible for the control of blood pressure. For over 30 years it has become the target for fighting off hypertension. Many inhibitors of the enzyme have been synthesized and used widely in medicine despite the lack of ACE structure. The last 5 years the crystal structure of ACE separate domains has been revealed, but in order to understand how the enzyme works it is necessary to study its structure in solution. We present here the cloning, overexpression in Escherichia coli, purification and structural study of the Ala(959) to Ser(1066) region (ACE_C) that corresponds to the C-catalytic domain of human somatic angiotensin-I-converting enzyme. ACE_C was purified under denatured conditions and the yield was 6 mg/l of culture. Circular dichroism (CD) spectroscopy indicated that 1,1,1-trifluoroethanol (TFE) is necessary for the correct folding of the protein fragment. The described procedure can be used for the production of an isotopically labelled ACE(959-1066) protein fragment in order to study its structure in solution by NMR spectroscopy.

  5. The effect of chemical anti-inhibitors on fibrinolytic enzymes and inhibitors

    DEFF Research Database (Denmark)

    Sidelmann, Johannes Jakobsen; Jespersen, J; Kluft, C;

    1997-01-01

    Fibrinolytic enzyme inhibitors hamper the determination of the specific fibrinolytic serine protease activity. Reportedly, chemical anti-inhibitors eliminate the influence of fibrinolytic inhibitors, but it remains unclear to what extent they change the specific activity of fibrinolytic serine pr...

  6. Angiotensin converting enzymes from human urine of mild hypertensive untreated patients resemble the N-terminal fragment of human angiotensin I-converting enzyme.

    Science.gov (United States)

    Casarini, D E; Plavinik, F L; Zanella, M T; Marson, O; Krieger, J E; Hirata, I Y; Stella, R C

    2001-01-01

    Angiotensin I-converting enzyme (ACE) activity was analyzed in human urine collected from mild hypertensive untreated patients. DEAE-cellulose chromatography using linear gradient elution revealed two forms of angiotensin I-converting enzyme, eluted in the conductivity of 0.75 and 1.25 mS. The fractions of each conductivity were pooled and submitted to direct gel filtration in an AcA-34 column, and the apparent molecular weights of urinary ACEs were estimated as 90 kDa (for ACE eluted in 0.75 mS) and 65 kDa (for ACE eluted in 1.25 mS). Both enzymes have a K(i) of the order of 10(-7) M for the specific inhibitors studied, and are able to hydrolyze luteinizing hormone-releasing hormone and N-acetyl-Ser-Asp-Lys-Pro as described for N-domain ACE. By Western blot analysis, both peaks were recognized by ACE-specific antibody Y4, confirming the molecular weight already described. A plate precipitation assay using monoclonal antibodies to the N-domain of ACE showed that both forms of ACE binds with all monoclonal antibodies to the active N-domain ACE, suggesting that these forms of human urine ACEs resemble the N-fragment of ACE. The HP2 ACE (65 kDa) is similar to low molecular weight (LMW) ACE from normal subjects, and the HP2 ACE (90 kDa) is different from high molecular weight (190 kDa) and LMW (65 kDa) normal ACEs. The 90 kDa ACE could have an important role in development of hypertension. It will be fundamental to elucidate the molecular mechanism responsible for the genesis of this isoform.

  7. 血管紧张素转化酶抑制剂和血管紧张素Ⅱ受体拮抗剂在慢性肾脏疾病治疗中的应用%Application of angiotensin-converting enzyme inhibitors and angiotensinⅡreceptor blockers in chronic kidney disease

    Institute of Scientific and Technical Information of China (English)

    林攀; 刘红

    2013-01-01

    血管紧张素转化酶抑制剂和血管紧张素Ⅱ受体拮抗剂是目前广泛使用的降压药。对肾脏疾病患者,这两类药物还有独立于降压作用之外的减少蛋白尿的作用,在保护肾功能、延缓肾脏疾病的进展方面起到了极其重要的作用。但使用血管紧张素转化酶抑制剂或血管紧张素Ⅱ受体拮抗剂也可能导致产生高钾血症、急性肾损伤等不良反应,妊娠、双侧肾动脉狭窄或容量不足等患者禁用,老年人或肾功能明显减退患者慎用。一般不建议联合使用血管紧张素转化酶抑制剂和血管紧张素Ⅱ受体拮抗剂。%Angiotensin-converting enzyme (ACE) inhibitors and angiotensinⅡreceptor blockers (ARB) have been widely used as antihypertensive drugs. Independent of their antihypertensive effect, they also have effect on proteinuria reduction, which plays an extremely important role in renoprotection and delaying progression of kidney disease. However, ACE inhibitors and ARB may also induce hyperkalemia, acute kidney injury and other adverse reactions. Thus they are forbidden to patients who are pregnant, with bilateral renal artery stenosis, or with insufifcient capacity. ACE inhibitors and ARB must be used with caution for the elderly or patients with signiifcantly impaired renal function. It is not recommended to use ACE inhibitors combined with ARB.

  8. Correlation between ultra-high performance liquid chromatography-tandem mass spectrometry and reversed-phase thin-layer chromatography hydrophobicity data for evaluation of angiotensin-converting enzyme inhibitors absorption.

    Science.gov (United States)

    Odovic, Jadranka V; Markovic, Bojan D; Injac, Rade D; Vladimirov, Sote M; Karljikovic-Rajic, Katarina D

    2012-10-05

    In this research seven ACE inhibitors (enalapril, quinapril, fosinopril, lisinopril, cilazapril, ramipril, benazepril) were studied to evaluate the correlation between their absorption and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS) and reversed-phase thin-layer chromatography (RP-TLC) hydrophobicity data (φ(0) or C(0) parameters, respectively). Their absorption values were in the range of 25-60%, while calculated KOWWIN logP values were from -0.94 to 6.61. Additionally, perindopril (absorption 70%, KOWWIN logP 2.59) and moexipril (absorption 22%, KOWWIN logP 3.36) were introduced for the theoretical considerations due to their high/low absorption values which were on the opposite sites in comparison with the majority of ACE inhibitors (25-60%). In the theoretical considerations it was shown that the solubility data (logS) must be considered, as independent variable, simultaneously with KOWWIN logP to obtain reliable correlation (r(2)=0.7208) between absorption and ACE inhibitors lipophilicity. As the main topic of this study, the relationships between literature available and absorption data predicted by multiple linear regression (MLR) using logS values besides chromatographically obtained hydrophobicity parameters C(0) (r(2)=0.6424) or φ(0) (r(2)=0.6762) were studied proving that these parameters could be used in ACE inhibitors absorption evaluation. The UHPLC-MS method provides the direct application of experimentally obtained φ(0) values that is the advantage of this method. For better MLR correlation of ACE inhibitors absorption with C(0) parameters (RP-TLC) and logS, mathematical conversion of C(0) parameters to logC(0) values was necessary based on requisite for probability value of regression analysis (P<0.05). The accordance and differences between hydrophobicity parameters obtained by UHPLC-MS and RP-TLC were defined.

  9. Structural characterization of angiotensin I-converting enzyme in complex with a selenium analogue of captopril.

    Science.gov (United States)

    Akif, Mohd; Masuyer, Geoffrey; Schwager, Sylva L U; Bhuyan, Bhaskar J; Mugesh, Govindasamy; Isaac, R Elwyn; Sturrock, Edward D; Acharya, K Ravi

    2011-10-01

    Human somatic angiotensin I-converting enzyme (ACE), a zinc-dependent dipeptidyl carboxypeptidase, is central to the regulation of the renin-angiotensin aldosterone system. It is a well-known target for combating hypertension and related cardiovascular diseases. In a recent study by Bhuyan and Mugesh [Org. Biomol. Chem. (2011) 9, 1356-1365], it was shown that the selenium analogues of captopril (a well-known clinical inhibitor of ACE) not only inhibit ACE, but also protect against peroxynitrite-mediated nitration of peptides and proteins. Here, we report the crystal structures of human testis ACE (tACE) and a homologue of ACE, known as AnCE, from Drosophila melanogaster in complex with the most promising selenium analogue of captopril (SeCap) determined at 2.4 and 2.35 Å resolution, respectively. The inhibitor binds at the active site of tACE and AnCE in an analogous fashion to that observed for captopril and provide the first examples of a protein-selenolate interaction. These new structures of tACE-SeCap and AnCE-SeCap inhibitor complexes presented here provide important information for further exploration of zinc coordinating selenium-based ACE inhibitor pharmacophores with significant antioxidant activity. © 2011 The Authors Journal compilation © 2011 FEBS.

  10. Structural characterization of angiotensin I-converting enzyme in complex with a selenium analogue of captopril

    Science.gov (United States)

    Akif, Mohd; Masuyer, Geoffrey; Schwager, Sylva L U; Bhuyan, Bhaskar J; Mugesh, Govindasamy; Isaac, R Elwyn; Sturrock, Edward D; Acharya, K Ravi

    2011-01-01

    Human somatic angiotensin I-converting enzyme (ACE), a zinc-dependent dipeptidyl carboxypeptidase, is central to the regulation of the renin–angiotensin aldosterone system. It is a well-known target for combating hypertension and related cardiovascular diseases. In a recent study by Bhuyan and Mugesh [Org. Biomol. Chem. (2011) 9, 1356–1365], it was shown that the selenium analogues of captopril (a well-known clinical inhibitor of ACE) not only inhibit ACE, but also protect against peroxynitrite-mediated nitration of peptides and proteins. Here, we report the crystal structures of human testis ACE (tACE) and a homologue of ACE, known as AnCE, from Drosophila melanogaster in complex with the most promising selenium analogue of captopril (SeCap) determined at 2.4 and 2.35 Å resolution, respectively. The inhibitor binds at the active site of tACE and AnCE in an analogous fashion to that observed for captopril and provide the first examples of a protein–selenolate interaction. These new structures of tACE–SeCap and AnCE–SeCap inhibitor complexes presented here provide important information for further exploration of zinc coordinating selenium-based ACE inhibitor pharmacophores with significant antioxidant activity. Database Structural data for the two SeCap complexes with ACE and AnCE have been deposited with the RCSB Protein Data Bank under the codes 2YDM and 3ZQZ, respectively. PMID:21810173

  11. Properties of soluble and particulate angiotensin-converting enzymes of rabbit lung, induced macrophage and serum.

    Science.gov (United States)

    Friedland, J; Silverstein, E

    1983-01-01

    Rabbit serum, lung and corticosteroid-induced macrophage angiotensin-converting enzymes were compared with respect to migration on polyacrylamide-gel electrophoresis, sucrose gradient centrifugation and Km. Cellular particulate enzymes solubilized by nonidet P40 had approximately half the electrophoretic mobility of soluble enzymes and a similar Km (1.2 mM). Trypsin treatment of nonidet P40 solubilized particulate enzyme converted its electrophoretic mobility to that of soluble enzyme, and rendered it non-aggregating in sucrose gradients lacking detergent, similar to soluble enzyme. Approximate molecular weights by sucrose gradient centrifugation were similar for all enzymes (135,000-158,000). The data suggest that lung and macrophage enzymes are similar and that cellular particulate enzyme may be convertible to soluble enzyme.

  12. Congestive heart failure and converting enzyme inhibition: failure of current prognostic criteria for predicting subsequent renal insufficiency.

    OpenAIRE

    1991-01-01

    Angiotensin-1-converting enzyme inhibitors have an effective and established role in the treatment of patients with congestive heart failure. However, a small number of such patients will subsequently develop renal insufficiency. These patients may be identified prior to, or shortly after, commencement of therapy by recognized criteria. This report describes 4 patients with congestive heart failure who developed severe renal insufficiency secondary to either enalapril or captopril therapy in ...

  13. 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

    DEFF Research Database (Denmark)

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

    2004-01-01

    deaths and hospitalizations until 2002. Mortality was analysed with Cox proportional hazard models and hospitalization with Poisson regression models (models adjusted for observation time). Over 10-12 years of follow-up, a total of 1283 deaths and 9220 hospitalizations were registered. Compared...... congestive heart failure hospitalizations (rate ratio 0.85, 95% CI 0.77-0.93, Pyears has long-term benefits. The beneficial effect on mortality and hospitalization rates is maintained for at least 10-12 years....... (ejection fractionyears. At study closure, all patients were recommended continued ACE-inhibitor use. National registries were used to track...

  14. Angiotensin converting enzyme 2 abrogates bleomycin-induced lung injury.

    Science.gov (United States)

    Rey-Parra, G J; Vadivel, A; Coltan, L; Hall, A; Eaton, F; Schuster, M; Loibner, H; Penninger, J M; Kassiri, Z; Oudit, G Y; Thébaud, B

    2012-06-01

    Despite substantial progress, mortality and morbidity of the acute respiratory distress syndrome (ARDS), a severe form of acute lung injury (ALI), remain unacceptably high. There is no effective treatment for ARDS/ALI. The renin-angiotensin system (RAS) through Angiotensin-converting enzyme (ACE)-generated Angiotensin II contributes to lung injury. ACE2, a recently discovered ACE homologue, acts as a negative regulator of the RAS and counterbalances the function of ACE. We hypothesized that ACE2 prevents Bleomycin (BLM)-induced lung injury. Fourteen to 16-week-old ACE2 knockout mice-male (ACE2(-/y)) and female (ACE2(-/-))-and age-matched wild-type (WT) male mice received intratracheal BLM (1.5U/kg). Male ACE2(-/y) BLM injured mice exhibited poorer exercise capacity, worse lung function and exacerbated lung fibrosis and collagen deposition compared with WT. These changes were associated with increased expression of the profibrotic genes α-smooth muscle actin (α-SMA) and Transforming Growth Factor ß1. Compared with ACE2(-/y) exposed to BLM, ACE2(-/-) exhibited better lung function and architecture and decreased collagen deposition. Treatment with intraperitoneal recombinant human (rh) ACE2 (2 mg/kg) for 21 days improved survival, exercise capacity, and lung function and decreased lung inflammation and fibrosis in male BLM-WT mice. Female BLM WT mice had mild fibrosis and displayed a possible compensatory upregulation of the AT2 receptor. We conclude that ACE2 gene deletion worsens BLM-induced lung injury and more so in males than females. Conversely, ACE2 protects against BLM-induced fibrosis. rhACE2 may have therapeutic potential to attenuate respiratory morbidity in ALI/ARDS.

  15. Silica Exposure and Serum Angiotensin Converting Enzyme Activity

    Directory of Open Access Journals (Sweden)

    YK Sharma

    2010-01-01

    Full Text Available 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 the serum ACE activity among quartz stone workers without disease.Methods: A cross-sectional study was carried out on 134 (111 men and 14 women workers of quartz stone crushing units were studied. Standard diagnostic criteria were used for diagnosing silicosis and tuberculosis. Pulmonary functions of the participants were also assessed.Results: The mean±SD age for participants was 26.1±6.3 years (26.6±6.3 for men and 21.9±4.3 for women. The mean±SD duration of exposure was 1.1±1.9 years. In the present study, only one case of silicosis and eight cases of tuberculosis were found. The mean±SD serum ACE levels for those with and without respiratory disease were 68.44±11.61, and 66.9±14.4 IU/L, respectively (p>0.05.Conclusion: We could not observe any association between serum ACE activity and age, gender, duration of exposure, smoking habits and pulmonary function status. However, elevated levels of serum ACE was found in a solitary case of silicosis.

  16. Enthalpy of captopril-angiotensin I-converting enzyme binding.

    Science.gov (United States)

    Ortiz-Salmerón, E; Barón, C; García-Fuentes, L

    1998-09-18

    High-sensitivity titration calorimetry is used to measure changes in enthalpy, heat capacity and protonation for the binding of captopril to the angiotensin I-converting enzyme (ACE; EC 3.4.15.1). The affinity of ACE to captopril is high and changes slightly with the pH, because the number of protons linked to binding is low. The determination of the enthalpy change at different pH values suggests that the protonated group in the captopril-ACE complex exhibits a heat protonation of approximately -30 kJ/mol. This value agrees with the protonation of an imidazole group. The residues which may become protonated in the complex could be two histidines existing in two active sites, which are joined to the amino acids coordinated to Zn2+. Calorimetric measurements indicate that captopril binds to two sites in the monomer of ACE, this binding being enthalpically unfavorable and being dominated by a large positive entropy change. Thus, binding is favored by both electrostatic and hydrophobic interactions. The temperature dependence of the free energy of binding deltaG degrees is weak because of the enthalpy-entropy compensation caused by a large heat capacity change, deltaCp =-4.3+/-0.1 kJ/K/mol of monomeric ACE. The strong favorable binding entropy and the negative deltaCp indicate both a large contribution to binding due to hydrophobic effects, which seem to originate from dehydration of the ligand-protein interface, and slight conformational changes in the vicinity of the active sites.

  17. Angiotensin-1 converting enzyme polymorphisms in chronic beryllium disease.

    Science.gov (United States)

    Maier, L A; Raynolds, M V; Young, D A; Barker, E A; Newman, L S

    1999-04-01

    To test the hypothesis that the angiotensin converting enzyme (ACE) genotype is associated with chronic beryllium disease (CBD) and disease severity, we studied 50 cases of CBD and compared their ACE genotype to that of two different control groups, consisting of: (1) 50 participants from a beryllium machining facility; and (2) 50 participants from a non-beryllium-associated workplace. We found no statistically significant difference in the frequency of the I or D allele or of the DD genotype among cases of CBD and either control group. The odds ratio (OR) for the CBD DD genotype as compared with the non-DD genotype was 1.58 (95% confidence interval [CI]: 0.68 to 3.66, p = 0.12) for the beryllium-exposed control group, and 1.09 (95% CI: 0.48 to 2.46, p = 0.56) for the non-beryllium-exposed controls. We found an association between serum ACE activity and the ACE genotype, with DD cases having the highest median serum ACE activity (p = 0.005). We evaluated the beryllium lymphocyte proliferation test (BeLPT), bronchoalveolar lavage (BAL) cell components, chest radiography, pulmonary function test results, and exercise physiology in our CBD cases. No statistically significant associations with these disease markers were found for the CBD cases with the DD genotype. Although the difference was not statistically significant, the DD cases had a shorter median duration of exposure to beryllium before diagnosis of CBD, and tended to have a weaker response in their blood and BAL BeLPT than did the non-DD cases. These findings may indicate that the ACE genotype is important in the immune response to beryllium and in progression to beryllium disease.

  18. The Effect of Angiotensin-Converting Enzyme Inhibition Using Captopril on Energy Balance and Glucose Homeostasis

    Science.gov (United States)

    de Kloet, Annette D.; Krause, Eric G.; Kim, Dong-Hoon; Sakai, Randall R.; Seeley, Randy J.; Woods, Stephen C.

    2009-01-01

    Increasing evidence suggests that the renin-angiotensin-system contributes to the etiology of obesity. To evaluate the role of the renin-angiotensin-system in energy and glucose homeostasis, we examined body weight and composition, food intake, and glucose tolerance in rats given the angiotensin-converting enzyme inhibitor, captopril (∼40 mg/kg · d). Rats given captopril weighed less than controls when fed a high-fat diet (369.3 ± 8.0 vs. 441.7 ± 8.5 g after 35 d; P captopril ate significantly less [3110.3 ± 57.8 vs. 3592.4 ± 88.8 kcal (cumulative 35 d high fat diet intake); P captopril caused animals to defend a lower body weight, animals in both groups were fasted for 24 h and subsequently restricted to 20% of their intake for 2 d. When free food was returned, captopril and control rats returned to their respective body weights and elicited comparable hyperphagic responses. These results suggest that angiotensin-converting enzyme inhibition protects against the development of diet-induced obesity and glucose intolerance. PMID:19497971

  19. Inhibition of angiotensin-converting enzyme increases oestradiol production in ewes submitted to oestrous synchronization protocol.

    Science.gov (United States)

    Costa, A s; Junior, A S; Viana, G E N; Muratori, M C S; Reis, A M; Costa, A P R

    2014-10-01

    This study aimed at evaluating the effects of angiotensin-converting enzyme inhibitor (enalapril) and angiotensin II antagonist (valsartan) on the oestradiol and progesterone production in ewes submitted to oestrous synchronization protocol. The animals were weighed and randomly divided into three groups (n = 7). A pre-experiment conducted to verify the effectiveness and toxicity of enalapril (0.5 mg/kg LW) and valsartan (2.2 mg/kg LW) showed that, in the doses used, these drugs were effective in reducing blood pressure without producing toxic effects. In the experiment, all animals were subjected to oestrous synchronization protocol during 12 days. On D10, D11 and D12, animals received saline, enalapril or valsartan (same doses of the pre-experiment), according to the group randomly divided. The hormonal analysis showed an increase in oestradiol on the last day of the protocol (D12) in animals that received enalapril (p sheep and that the angiotensin-converting enzyme (ACE) inhibition with enalapril leads to an increase in oestradiol production near ovulation without changing the concentration of progesterone. This shows that ACE inhibition may be a useful tool in reproductive biotechnologies involving induction and synchronization of oestrus and ovulation in sheep.

  20. Generation of a 90 000 molecular weight fragment from human plasma angiotensin-I-converting enzyme by enzymatic or alkaline hydrolysis.

    Science.gov (United States)

    Yotsumoto, H; Lanzillo, J J; Fanburg, B L

    1983-12-12

    A catalytically active Mr 90 000 fragment was generated from native Mr 140 000 human plasma angiotensin-I-converting enzyme after treatment with reagents that induced a perturbation of the native tertiary conformation. Treatment of converting enzyme with 6 M urea produced an aggregation of molecules that was susceptible to proteolysis by either trypsin, chymotrypsin or Staphylococcus aureus V8 proteinase to generate the Mr 90 000 converting enzyme. Also, 1 M ammonium hydroxide, pH 11.3, or 0.01 M sodium hydroxide, pH 11.3, cleaved converting enzyme to the Mr 90 000 fragment. Degradation was not an autocatalytic phenomenon, since it was not prevented by inhibition of converting enzyme with EDTA. The enzymatically mediated, but not the alkaline mediated, cleavage was inhibited by specific converting enzyme inhibitors captopril and Merck L-154,826. This suggests that captopril and Merck L-154,826 can prevent converting-enzyme degradation by preserving a conformation that does not have sites exposed to proteolytic enzymes. This conformation may mimic the native conformation which is quite resistant to serine proteinases.

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

    Science.gov (United States)

    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).

  2. Prediction of severe hypoglycaemia by angiotensin-converting enzyme activity and genotype in type 1 diabetes

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, U; Agerholm-Larsen, Birgit; Pramming, S

    2003-01-01

    AIMS/HYPOTHESIS: We have previously shown a strong relationship between high angiotensin-converting enzyme (ACE) activity, presence of the deletion (D) allele of the ACEgene and recall of severe hypoglycaemic events in patients with Type 1 diabetes. This study was carried out to assess...... this relationship prospectively. METHODS: We followed 171 adult outpatients with Type 1 diabetes in a one-year observational study with the recording of severe hypoglycaemia. Participants were characterised by serum ACE activity and ACE genotype and not treated with ACE inhibitors or angiotensin II receptor...... antagonists. RESULTS: There was a positive relationship between serum ACE activity and rate of severe hypoglycaemia with a 2.7 times higher rate in the fourth quartile of ACE activity compared to the first quartile (p=0.0007). A similar relationship was observed for the subset of episodes with coma (2.9 times...

  3. A common haplotype on methylenetetrahydrofolate reductase gene modifies the effect of angiotensin-converting enzyme inhibitor on blood pressure in essential hypertension patients--a family-based association study.

    Science.gov (United States)

    Jiang, Shanqun; Hsu, Yi-Hsiang; Niu, Tianhua; Xu, Xin; Xing, Houxun; Chen, Changzhong; Wang, Xiaobin; Zhang, Yan; Peng, Shaojie; Xu, Xiping

    2005-08-01

    Our recent study indicated that MTHFR C677T polymorphism may involve in genetic control of blood pressure response to treatment by benazepril, an ACE inhibitor. Currently, we proposed to further investigate whether short-term blood pressure response to benazepril, was modulated by haplotypes re-constructed from both C677T and A1298C polymorphisms in MTHFR gene. A total of 410 hypertensive patients recruited from 344 nuclear families were treated orally with benazepril at a daily dosage of 10 mg for 15 consecutive days. Blood pressures were measured at baseline and on the 16th day of treatment. In addition, 689 family members of these patients were also genotyped. Among these patients, the frequency of MTHFR A1298C AA, AC and CC genotypes was 74.4%, 23.9%, and 1.7%, respectively. The frequency of MTHFR C677T CC, CT and TT genotypes was 23.7%, 51.2%, and 25.1%, respectively. Only three haplotypes, 677T-1298A (50.8%), 677C-1298A (35.7%), and 677C-1298C (13.5%) were re-constructed. Multivariate regression models with generalized estimating equation (GEE) correction detected that the individuals carrying one copy of haplotype 677C-1298C had significantly lower diastolic and systolic blood pressure response (DeltaDBP and DeltaSBP) to benazepril treatment (p= 0.003 and p =0.043, respectively), in comparison to those without haplotype 677C-1298C. The results of family-based association test further confirmed that haplotype 677C-1298C was more frequently transmitted in subjects with either lower residual of DeltaDBP or DeltaSBP. For residual of DeltaDBP, the p-values are 0.007 in an additive model and 0.005 in a dominant model. For residual of DeltaSBP, the p-values are 0.009 in an additive model and 0.006 in a dominant model. Our findings suggest that MTHFR 677C-1298C haplotype modulate blood pressure responsiveness to shortterm treatment of ACE inhibitor in Chinese essential hypertensive patients.

  4. Chebulin: Terminalia chebula Retz. fruit-derived peptide with angiotensin-I-converting enzyme inhibitory activity.

    Science.gov (United States)

    Sornwatana, Thakorn; Bangphoomi, Kunan; Roytrakul, Sittiruk; Wetprasit, Nuanchawee; Choowongkomon, Kiattawee; Ratanapo, Sunanta

    2015-01-01

    Angiotensin-I-converting enzyme (ACE) plays an important role in blood pressure regulation. In this study, an ACE-hexapeptide inhibitor (Asp-Glu-Asn-Ser-Lys-Phe) designated as chebulin was produced from the fruit protein of Terminalia chebula Retz. by pepsin digestion, ultrafiltrated through a 3 KDa cut-off membrane, a reverse-phase high-performance liquid chromatography, and nano-liquid chromatography tandem mass spectrometry analysis. Chebulin was found to inhibit ACE in a noncompetitive manner, as supported by the structural model. It bounds to ACE by the hydrogen bond, hydrophobic and ionic interactions via the interactions of C-terminal Phe (Phe-6), and N-terminal residues (Asp-1 and Glu-2) with the amino acid residues on noncatalytic sites of the ACE. The results showed that chebulin derived from fruits of T. chebula Retz. is a potential ACE-peptide inhibitor that could be used as a functional food additive for the prevention of hypertension and as an alternative to ACE inhibitor drug.

  5. Alterations in circulatory and renal angiotensin-converting enzyme and angiotensin-converting enzyme 2 in fetal programmed hypertension.

    Science.gov (United States)

    Shaltout, Hossam A; Figueroa, Jorge P; Rose, James C; Diz, Debra I; Chappell, Mark C

    2009-02-01

    Antenatal betamethasone treatment is a widely accepted therapy to accelerate lung development and improve survival in preterm infants. However, there are reports that infants who receive antenatal glucocorticoids exhibit higher systolic blood pressure in their early adolescent years. We have developed an experimental model of programming whereby the offspring of pregnant sheep administered clinically relevant doses of betamethasone exhibit elevated blood pressure. We tested the hypothesis as to whether alterations in angiotensin-converting enzyme (ACE), ACE2, and neprilysin in serum, urine, and proximal tubules are associated with this increase in mean arterial pressure. Male sheep were administered betamethasone (2 doses of 0.17 mg/kg, 24 hours apart) or vehicle at the 80th day of gestation and delivered at term. Sheep were instrumented at adulthood (1.8 years) for direct conscious recording of mean arterial pressure. Serum and urine were collected and proximal tubules isolated from the renal cortex. Betamethasone-treated animals had elevated mean arterial pressure (97+/-3 versus 83+/-2 mm Hg; P<0.05) and a 25% increase in serum ACE activity (48.4+/-7.0 versus 36.0+/-2.7 fmol/mL per minute) but a 40% reduction in serum ACE2 activity (18.8+/-1.2 versus 31.4+/-4.4 fmol/mL per minute). In isolated proximal tubules, ACE2 activity and expression were 50% lower in the treated sheep with no significant change in ACE or neprilysin activities. We conclude that antenatal steroid treatment results in the chronic alteration of ACE and ACE2 in the circulatory and tubular compartments, which may contribute to the higher blood pressure in this model of fetal programming-induced hypertension.

  6. [Effects of hydroxyl radicals on purified angiotensin I converting enzyme].

    Science.gov (United States)

    Michel, B; Nirina, L B; Grima, M; Ingert, C; Coquard, C; Barthelmebs, M; Imbs, J L

    1998-08-01

    Somatic angiotensin-converting enzyme (ACE) is a protein which contains two similar domains (N and C), each possessing a functional active site. The relationship between ACE, its natural substrates and oxygen free radicals is starting to be explored. On one hand, superoxide anions production is induced by angiotensin II and on the other hand, activated polynuclear neutrophils, through free radicals generation, alter endothelial ACE activity. In this study, we examined the impact of hydroxyl radicals (.OH) on purified ACE. .OH were produced using a generator: 2,2'-azo-bis 2-amidinopropane (GRH) provided by Lara-Spiral (Fr). GRH (3 mM), in a time-dependent fashion, inhibited ACE activity. When ACE was co-incubated for 4 h with GRH, its activity decreased by 70%. Addition of dimethylthiourea (DMTU: 0.03 to 1 mM) or mannitol + methionine (20/10 mM), two sets of .OH scavengers, produced a dose-dependent protection on ACE activity. To examine whether oxidation of thiol groups in the ACE molecule could be involved in the action of GRH, the effects of thiol reducing agents: mercaptoethanol and dithiotreitol (DTT) were investigated. These compounds produced a dose-dependent and significant protection; with 100% protection at 0.2 and 0.3 mM for mercaptoethanol and at 0.1 mM for DTT. The hydrolysis of two natural and domain-specific substrates were also explored. The hydrolysis of angiotensin I preferentially cleaved by the C domain was significantly (p GRH [in nmol angio II formed/min/nmol of ACE, n = 4; 35.9 +/- 0.6 (control), 15.5 +/- 2.8 (GRH : 0.3 mM), 15.1 +/- 0.5 (1), 10.9 +/- 0.6 (3)]. The hydrolysis of the hemoregulatory peptide (hp), preferential substrate for the N domain was not affected by GRH at 0.3 mM and inhibited by 28% (not significant) by 1 mM GRH [in nmol ph hydrolized/min/nmol ACE, n = 4; 12.6 +/- 1.9 (control), 14.9 (GRH : 0.3 mM), 8.3 +/- 4.0 (1). These results demonstrated that .OH affect ACE activity and could suggest a privileged impact of GRH on the

  7. Angiotensin-converting enzyme D/I and plasminogen activator inhibitor-1 4G/5G gene polymorphisms are associated with increased risk of spontaneous abortions in polycystic ovarian syndrome.

    Science.gov (United States)

    Sun, L; Lv, H; Wei, W; Zhang, D; Guan, Y

    2010-02-01

    Polycystic ovary syndrome (PCOS) is a main cause of infertility, particularly in high-risk settings such as spontaneous abortions (SAB). We aimed to evaluate the effect of genetic polymorphisms in ACE and plasminogen activator inhibitor-1 (PAI-1) on the occurrence of SAB in PCOS. One hundred and forty-two PCOS patients (83 women have a history of one or more unexplained SAB, 59 women have successfully live births) and 107 healthy controls matched for age and body mass index were included in the study. Levels of PAI-1, LH, FSH, testosterone, fasting glucose and insulin were measured. ACE deletion (D)/insertion (I) and PAI-1 4G/5G gene polymorphisms were performed. The D/D and/or 4G/4G genotype frequency, the D or 4G allelic frequency, the combination of the ACE D/D and PAI-1 4G/5G, D/I and 4G/4G genotypes of PCOS patients with SAB women were statistically higher than non-SAB group (p4G/4G or D/D genotype of PCOS with SAB patients had significantly higher PAI-1 levels than non-SAB women. The ACE D/I and PAI-1 4G/5G gene polymorphisms might represent risk factor in PCOS with SAB. Homozygosity for ACE D or PAI-1 4G polymorphisms as well as compound carrier status are significant positive explanatory variable for PCOS patients with SAB, which may result in increased PAI-1 concentrations and hypofibrinolysis and contribute to early pregnancy loss.

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

    DEFF Research Database (Denmark)

    Hansen, EF; Bendtsen, F; Henriksen, Jens Henrik Sahl

    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...... and enalapril reduced plasma angiotensin converting enzyme activity substantially and equally at six hr (-70%, Penzyme activity remained significantly suppressed only after lisinopril (-60%, P

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

    DEFF Research Database (Denmark)

    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...... and enalapril reduced plasma angiotensin converting enzyme activity substantially and equally at six hr (-70%, Penzyme activity remained significantly suppressed only after lisinopril (-60%, P

  10. Measurement of enzyme kinetics and inhibitor constants using enthalpy arrays.

    Science.gov (United States)

    Recht, Michael I; Torres, Frank E; De Bruyker, Dirk; Bell, Alan G; Klumpp, Martin; Bruce, Richard H

    2009-05-15

    Enthalpy arrays enable label-free, solution-based calorimetric detection of molecular interactions in a 96-detector array format. Compared with conventional calorimetry, enthalpy arrays achieve a significant reduction of sample volume and measurement time through the combination of the small size of the detectors and ability to perform measurements in parallel. The current capabilities of the technology for studying enzyme-catalyzed reactions are demonstrated by determining the kinetic parameters for reactions with three model enzymes. In addition, the technology has been used with two classes of enzymes to determine accurate inhibitor constants for competitive inhibitors from measurements at a single inhibitor concentration.

  11. Effect of phlorotannins isolated from Ecklonia cava on angiotensin I-converting enzyme (ACE) inhibitory activity.

    Science.gov (United States)

    Wijesinghe, W A J P; Ko, Seok-Chun; Jeon, You-Jin

    2011-04-01

    Inhibition of angiotensin I-converting enzyme (ACE) activity is the most common mechanism underlying the lowering of blood pressure. In the present study, five organic extracts of a marine brown seaweed Ecklonia cava were prepared by using ethanol, ethyl acetate, chloroform, hexane, and diethyl ether as solvents, which were then tested for their potential ACE inhibitory activities. Ethanol extract showed the strongest ACE inhibitory activity with an IC(50) value of 0.96 mg/ml. Five kinds of phlorotannins, phloroglucinol, triphlorethol-A, eckol, dieckol, and eckstolonol, were isolated from ethanol extract of E. cava, which exhibited potential ACE inhibition. Dieckol was the most potent ACE inhibitor and was found to be a non-competitive inhibitor against ACE according to Lineweaver-Burk plots. Dieckol had an inducible effect on the production of NO in EAhy926 cells without having cytotoxic effect. The results of this study indicate that E. cava could be a potential source of phlorotannins with ACE inhibitory activity for utilization in production of functional foods.

  12. The expression of testosterone converting enzymes in adipose tissue of polycystic ovary syndrome rat mode

    Institute of Scientific and Technical Information of China (English)

    王丽华

    2013-01-01

    Objective To establish a polycystic ovary syndrome(PCOS) rat model and compare the expression of testosterone converting enzymes in adipose tissue of PCOS rat with that of controls.Methods 21-day-old female SD

  13. Cerebrovascular effects of angiotensin converting enzyme inhibition involve large artery dilatation in rats

    DEFF Research Database (Denmark)

    Postiglione, A; Bobkiewicz, T; Vinholdt-Pedersen, E

    1991-01-01

    The aim of the study was to selectively examine the effects of converting enzyme inhibition on the large brain arteries by using concomitant inhibition of carbonic anhydrase to cause severe dilatation of mainly parenchymal resistance vessels....

  14. Angiotensin-converting enzyme gene I/D polymorphism in Pakistani ...

    African Journals Online (AJOL)

    hope&shola

    system, as its main role is to process angiotensin I to angiotensin II and degrade bradykinin. Human .... that is characterized by the presence or absence of a. 287bpAlu repeat .... angiotensin I converting enzyme using monoclonal antibodies.

  15. Renal oxygen content is increased in healthy subjects after angiotensin-converting enzyme inhibition

    Directory of Open Access Journals (Sweden)

    Anna Stein

    2012-07-01

    Full Text Available OBJECTIVE: The association between renal hypoxia and the development of renal injury is well established. However, no adequate method currently exists to non-invasively measure functional changes in renal oxygenation in normal and injured patients. METHOD: R2* quantification was performed using renal blood oxygen level-dependent properties. Five healthy normotensive women (50±5.3 years underwent magnetic resonance imaging in a 1.5T Signa Excite HDx scanner (GE Healthcare, Waukesha, WI. A multiple fast gradient-echo sequence was used to acquire R2*/T2* images (sixteen echoes from 2.1 ms/slice to 49.6 ms/slice in a single breath hold per location. The images were post-processed to generate R2* maps for quantification. Data were recorded before and at 30 minutes after the oral administration of an angiotensin II-converting enzyme inhibitor (captopril, 25 mg. The results were compared using an ANOVA for repeated measurements (mean + standard deviation followed by the Tukey test. ClinicalTrials.gov: NCT01545479. RESULTS: A significant difference (p<0.001 in renal oxygenation (R2* was observed in the cortex and medulla before and after captopril administration: right kidney, cortex = 11.08 ± 0.56ms, medulla = 17.21 ± 1.47ms and cortex = 10.30 ± 0.44ms, medulla = 16.06 ± 1.74ms, respectively; and left kidney, cortex= 11.79 ± 1.85ms, medulla = 17.03 ± 0.88ms and cortex = 10.89 ± 0.91ms, medulla = 16.43 ± 1.49ms, respectively. CONCLUSIONS: This result suggests that the technique efficiently measured alterations in renal blood oxygenation after angiotensin II-converting enzyme inhibition and that it may provide a new strategy for identifying the early stages of renal disease and perhaps new therapeutic targets.

  16. Increased urinary angiotensin-converting enzyme 2 in renal transplant patients with diabetes.

    Directory of Open Access Journals (Sweden)

    Fengxia Xiao

    Full Text Available Angiotensin-converting enzyme 2 (ACE2 is expressed in the kidney and may be a renoprotective enzyme, since it converts angiotensin (Ang II to Ang-(1-7. ACE2 has been detected in urine from patients with chronic kidney disease. We measured urinary ACE2 activity and protein levels in renal transplant patients (age 54 yrs, 65% male, 38% diabetes, n = 100 and healthy controls (age 45 yrs, 26% male, n = 50, and determined factors associated with elevated urinary ACE2 in the patients. Urine from transplant subjects was also assayed for ACE mRNA and protein. No subjects were taking inhibitors of the renin-angiotensin system. Urinary ACE2 levels were significantly higher in transplant patients compared to controls (p = 0.003 for ACE2 activity, and p≤0.001 for ACE2 protein by ELISA or western analysis. Transplant patients with diabetes mellitus had significantly increased urinary ACE2 activity and protein levels compared to non-diabetics (p<0.001, while ACE2 mRNA levels did not differ. Urinary ACE activity and protein were significantly increased in diabetic transplant subjects, while ACE mRNA levels did not differ from non-diabetic subjects. After adjusting for confounding variables, diabetes was significantly associated with urinary ACE2 activity (p = 0.003 and protein levels (p<0.001, while female gender was associated with urinary mRNA levels for both ACE2 and ACE. These data indicate that urinary ACE2 is increased in renal transplant recipients with diabetes, possibly due to increased shedding from tubular cells. Urinary ACE2 could be a marker of renal renin-angiotensin system activation in these patients.

  17. Different contributions of the angiotensin-converting enzyme C-domain and N-domain in subjects with the angiotensin-converting enzyme II and DD genotype.

    NARCIS (Netherlands)

    Esch, JH van; Gool, JM van; Bruin, R.J. de; Payne, J.R.; Montgomery, Henry; Hectors, M.; Deinum, J.; Dive, V.; Danser, A.H.

    2008-01-01

    BACKGROUND: Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism-related differences in ACE concentration do not result in differences in angiotensin levels. METHODS AND RESULTS: To investigate whether this relates to differences in the contribution of the ACE C-domain and

  18. Inhibitory activity of Plantago major L. on angiotensin I-converting enzyme.

    Science.gov (United States)

    Nhiem, Nguyen Xuan; Tai, Bui Huu; Van Kiem, Phan; Van Minh, Chau; Cuong, Nguyen Xuan; Tung, Nguyen Huu; Thu, Vu Kim; Trung, Trinh Nam; Anh, Hoang Le Tuan; Jo, Sung-Hoon; Jang, Hae-Dong; Kwon, Young-In; Kim, Young Ho

    2011-03-01

    Eight compounds were isolated from methanol extract of Plantago major L. leaves and investigated for their ability to inhibit angiotensin I-converting enzyme activity. Among them, compound 1 showed the most potent inhibition with rate of 28.06 ± 0.21% at a concentration of 100 μM. Compounds 2 and 8 exhibited weak activities. These results suggest that compound 1 might contribute to the ability of P. major to inhibit the activity of angiotensin I- converting enzyme.

  19. ADDITIVE ANTIPROTEINURIC EFFECT OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITION AND NONSTEROIDAL ANTIINFLAMMATORY DRUG-THERAPY - A CLUE TO THE MECHANISM OF ACTION

    NARCIS (Netherlands)

    HEEG, JE; DEJONG, PE; DEZEEUW, D

    1. Both the angiotensin-converting enzyme inhibitor, lisinopril, and the non-steroidal anti-inflammatory drug, indomethacin, lower urinary protein excretion in renal disease and improve the selectivity of the residual proteinuria. Despite the clearly different renal haemodynamic profiles of the two

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Substrate phosphorylation affects degradation and interaction to endopeptidase 24.15, neurolysin, and angiotensin-converting enzyme.

    Science.gov (United States)

    Machado, M F M; Cunha, F M; Berti, D A; Heimann, A S; Klitzke, C F; Rioli, V; Oliveira, V; Ferro, E S

    2006-01-13

    Recent findings from our laboratory suggest that intracellular peptides containing putative post-translational modification sites (i.e., phosphorylation) could regulate specific protein interactions. Here, we extend our previous observations showing that peptide phosphorylation changes the kinetic parameters of structurally related endopeptidase EP24.15 (EC 3.4.24.15), neurolysin (EC 3.4.24.16), and angiotensin-converting enzyme (EC 3.4.15.1). Phosphorylation of peptides that are degraded by these enzymes leads to reduced degradation, whereas phosphorylation of peptides that interacted as competitive inhibitors of these enzymes alters only the K(i)'s. These data suggest that substrate phosphorylation could be one of the mechanisms whereby some intracellular peptides would escape degradation and could be regulating protein interactions within cells.

  2. 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

    Institute of Scientific and Technical Information of China (English)

    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.

  3. Angiotensin I-converting enzyme inhibitory peptide derived from glycinin, the 11S globulin of soybean (Glycine max).

    Science.gov (United States)

    Mallikarjun Gouda, K G; Gowda, Lalitha R; Rao, A G Appu; Prakash, V

    2006-06-28

    Angiotensin I-converting enzyme (ACE), a dipeptidyl carboxypeptidase, catalyzes the conversion of Angiotensin I to the potent vasoconstrictor Angiotensin II and plays an important physiological role in regulating blood pressure. Inhibitors of angiotensin 1-converting enzyme derived from food proteins are utilized for pharmaceuticals and physiologically functional foods. ACE inhibitory properties of different enzymatic hydrolysates of glycinin, the major storage protein of soybean, have been demonstrated. The IC50 value for the different enzyme digests ranges from 4.5 to 35 microg of N2. The Protease P hydrolysate contained the most potent suite of ACE inhibitory peptides. The ACE inhibitory activity of the Protease P hydrolysate after fractionation by RP-HPLC and ion-pair chromatography was ascribed to a single peptide. The peptide was homogeneous as evidenced by MALDI-TOF and identified to be a pentapeptide. The sequence was Val-Leu-Ile-Val-Pro. This peptide was synthesized using solid-phase FMOC chemistry. The IC50 for ACE inhibition was 1.69 +/- 0.17 microM. The synthetic peptide was a potent competitive inhibitor of ACE with a Ki of 4.5 +/- 0.25 x 10(-6) M. This peptide was resistant to digestion by proteases of the gastrointestinal tract. The antihypertensive property of this peptide derived from glycinin might find importance in the development of therapeutic functional foods.

  4. Effects of angiotensin-converting enzyme inhibition on altered renal hemodynamics induced by low protein diet in the rat.

    OpenAIRE

    Fernández-Repollet, E; Tapia, E; Martínez-Maldonado, M

    1987-01-01

    We assessed the role of angiotensin II in mediating the alterations in renal hemodynamics known to result from low protein feeding to normal rats by examining the effect of the angiotensin-converting enzyme (ACE) inhibitor captopril. 2 wk of low protein (6% casein) diet resulted in decreased glomerular filtration rate (normal protein [NP], 1.82 +/- 0.17 vs. low protein [LP], 0.76 +/- 0.01 ml/min; P less than 0.05) and renal plasma flow (NP, 6.7 +/- 0.2 vs. LP, 3.3 +/- 0.3 ml/min; P less than ...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    . The diagnosis is often delayed and traditional treatment usually ineffective. Complement C1 inhibitor concentrate and bradykinin receptor antagonists, normally used to treat patients with hereditary angioedema, have shown good results when used in patients with bradykinin-mediated angioedema. This review......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...

  6. Angiotensin converting enzyme in Alzheimer's disease increased activity in caudate nucleus and cortical areas.

    Science.gov (United States)

    Arregui, A; Perry, E K; Rossor, M; Tomlinson, B E

    1982-05-01

    The activity of the dipeptidyl carboxypeptidase, angiotensin converting enzyme, was assayed in several brain regions of patients dying with Alzheimer's disease and compared to that of appropriately age-matched controls. Enzyme activity was found to be elevated by 44% and 41% in the medial hippocampus and parahippocampal gyrus, respectively, and by 27% and 29% in the frontal cortex (area 10 of Brodman) and caudate nucleus, respectively, in Alzheimer's disease patients. Converting enzyme activity did not differ from controls in the nucleus accumbens, substantia nigra, temporal cortex, anterior or posterior hippocampus, amydgala, and septal nuclei.

  7. Angiotensin-converting enzyme in acute myocardial infarction and angina pectoris.

    Science.gov (United States)

    Rømer, F K; Kornerup, H J

    1981-06-01

    Serum activity of angiotensin-converting enzyme was measured by serial analysis in 19 patients with acute myocardial infarction and in eight patients with angina pectoris. As a rule no changes in enzyme activity occurred during 6 days observations. However, two patients with infarction exhibited a pronounced fall of enzyme activity which could not be related to clinical events. The analysis seems to have no place in the diagnosis and management of patients with myocardial infarction.

  8. Natural and Synthetic Macrocyclic Inhibitors of the Histone Deacetylase Enzymes

    DEFF Research Database (Denmark)

    Maolanon, Alex; Kristensen, Helle; Leman, Luke

    2017-01-01

    Inhibition of histone deacetylase (HDAC) enzymes has emerged as a target for development of cancer chemotherapy. Four compounds have gained approval for clinical use by the Food and Drug Administration (FDA) in the US, and several are currently in clinical trials. However, none of these compounds...... HDAC enzymes may hold an advantage over traditional hydroxamic acid-containing inhibitors, which rely on chelation to the conserved active site zinc ion. Here, we review the literature on macrocyclic HDAC inhibitors obtained from natural sources and structure-activity relationship studies inspired...

  9. Inhibitors of Nucleotidyltransferase Superfamily Enzymes Suppress Herpes Simplex Virus Replication

    OpenAIRE

    2014-01-01

    Herpesviruses are large double-stranded DNA viruses that cause serious human diseases. Herpesvirus DNA replication depends on multiple processes typically catalyzed by nucleotidyltransferase superfamily (NTS) enzymes. Therefore, we investigated whether inhibitors of NTS enzymes would suppress replication of herpes simplex virus 1 (HSV-1) and HSV-2. Eight of 42 NTS inhibitors suppressed HSV-1 and/or HSV-2 replication by >10-fold at 5 μM, with suppression at 50 μM reaching ∼1 million-fold. Five...

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Wound healing, angiotensin-converting enzyme inhibition, and collagen-containing products: a case study.

    Science.gov (United States)

    Buscemi, Charles P; Romeo, CarolAnn

    2014-01-01

    The effects of multiple medications may impair or enhance wound healing. A review of the literature for drug side effects identified cell culture and case studies of angiotensin-converting enzyme inhibitors (ACEIs) impairing collagen deposition in cutaneous wounds; these medications have also been used to prevent or minimize keloid formation. A 71-year-old male patient presented with a venous leg ulcer (VLU), having incurred a crushing injury and fracture requiring surgical repair 16 years earlier. The patient's history was significant for obesity, smoking 1 cigar daily, hypertension, and lower extremity venous insufficiency; medications included amlodipine and lisinopril. The wound initially responded well to advanced wound products and compression, but wound healing subsequently stalled. A collagen-containing alginate dressing was added to the treatment regimen and the wound closed within 2 weeks. We postulate that lisinopril may have contributed to the observed delayed healing and targeted this potential impediment to wound healing with a readily available topical collagen-containing product resulting in a rapid wound closure after a significant delay in progress toward wound healing.

  12. Angiotensin-converting Enzyme Inhibition Improves the Effectiveness of Transcutaneous Carbon Dioxide Treatment.

    Science.gov (United States)

    Nemeth, Balazs; Kiss, Istvan; Jencsik, Timea; Peter, Ivan; Kreska, Zita; Koszegi, Tamas; Miseta, Attila; Kustan, Peter; Boncz, Imre; Laczo, Andrea; Ajtay, Zeno

    2017-01-01

    To study the effect of carbon dioxide (CO2) therapy on the nitric oxide (NO) pathway by monitoring plasma asymmetric dimethylarginine (ADMA) concentrations. Forty-seven hypertensive patients who underwent transcutaneous CO2 therapy were enrolled. Thirty healthy individuals were recruited for the control group. Blood samples were taken one hour before, as well as one hour, 24 hours and 3 weeks after the first CO2 treatment. Controls did not undergo CO2 treatment. Plasma ADMA levels were measured by ELISA. ADMA levels decreased significantly one hour after the first CO2 treatment compared to the baseline concentrations (p=0.003). Significantly greater reduction was found among patients in whom angiotensin converting enzyme inhibitors (ACEIs) were administered (p=0.019). The short- and long-term decrease of ADMA levels suggests that CO2 is not only a vasodilator, but also has a beneficial effect on the NO pathway. ACE inhibition seems to enhance the effect of CO2 treatment. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  13. Eritadenine from Edible Mushrooms Inhibits Activity of Angiotensin Converting Enzyme in Vitro.

    Science.gov (United States)

    Afrin, Sadia; Rakib, Md Abdur; Kim, Boh Hyun; Kim, Jeong Ok; Ha, Yeong Lae

    2016-03-23

    The inhibition of angiotensin converting enzyme (ACE) activity was determined in vitro by mushroom-derived eritadenine (EA), which was analyzed in 11 principal Korean edible mushrooms. EA inhibited ACE activity with 0.091 μM IC50, whereas the IC50 of captopril (CP), which is a reference compound, was 0.025 μM. Kinetic measurements of ACE reaction in the substrate of hippuryl-l-histidyl-l-leucine (HHL) with or without EA revealed that the Vmax (0.0465 O.D/30 min) was unchanged, but the the Km increased from 2.063 to 3.887 mM, indicating that EA competes with HHL for the active site. When EA was analyzed by HPLC, Lentinus edodes with a soft cap contained the highest amount EA (642.8 mg%); however, Phellinus linteus with a hard cap contained the least amount of EA (9.4 mg%). These results indicate that EA was a strong competitive inhibitor for ACE, and edible mushrooms with soft caps contained a significant amount of EA.

  14. Direct radio-immunoassay of renin substrate: effect of converting enzyme inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Metsaerinne, Kaj; Rosenloef, Katarina; Groenhagen-Riska, Carola; Fyhrquist, Frej

    1988-02-01

    A direct radio-immunoassay (RIA) for renin substrate (RS) was compared to enzymatic (indirect) assay. In normal subjects, a significant, albeit weak, correlation between the methods was seen. In hypertensive patients with different levels of plasma renin activity (PRA), RS concentration measured by both assays increased with increasing PRA, and for patients with PRA > 10 ..mu..g AI/l/h, direct assay gave significantly higher RS values (55%), compared to the enzymatic assay, indicating consumption of RS by increasing plasma renin and production rate of RS with increasing PRA. In 11 patients with renovascular hypertension, treatment with angiotensin-converting enzyme (ACE) inhibitor, lisinopril, resulted in a significant increase in PRA, accompanied by a decrease in RS measured by enzymatic assay. No change in RS measured by direct RIA was noticed. The results suggest that ACE inhibition may not have an effect upon RS production and that its effect on plasma RS is limited to a reduction of intact RS measured by the enzymatic assay.

  15. Angiotensin-converting enzyme gene insertion/deletion polymorphism in migraine patients

    Directory of Open Access Journals (Sweden)

    White Linda R

    2008-03-01

    Full Text Available Abstract Background The main objective of this study was to investigate the angiotensin converting enzyme (ACE genotype as a possible risk factor for migraine (both with and without aura compared to controls. We also wanted to examine whether a clinical response to an ACE inhibitor, lisinopril, or an angiotensin II receptor blocker, candesartan, in migraine prophylaxis was related to ACE genotype. Methods 347 migraine patients aged 18–68 (155 migraine without aura (MoA, 187 migraine with aura (MwA and 5 missing aura subgroup data and 403 healthy non-migrainous controls > 40 years of age were included in the study. A polymerase chain reaction (PCR was performed on the genomic DNA samples to obtain the ACE insertion (I/deletion(D polymorphisms. Results No significant differences between migraine patients and controls were found with regard to ACE genotype and allele distributions. Furthermore, there was no significant difference between the controls and the MwA or MoA subgroups. Conclusion In our sample there is no association between ACE genotype or allele frequency and migraine. In addition, ACE genotype in our experience did not predict the clinical response to lisinopril or candesartan used as migraine prophylactics.

  16. Angiotensin I-Converting Enzyme Inhibitory Peptides of Chia (Salvia hispanica Produced by Enzymatic Hydrolysis

    Directory of Open Access Journals (Sweden)

    Maira Rubi Segura Campos

    2013-01-01

    Full Text Available Synthetic angiotensin I-converting enzyme (ACE-I inhibitors can have undesirable side effects, while natural inhibitors have no side effects and are potential nutraceuticals. A protein-rich fraction from chia (Salvia hispanica L. seed was hydrolyzed with an Alcalase-Flavourzyme sequential system and the hydrolysate ultrafiltered through four molecular weight cut-off membranes (1 kDa, 3 kDa, 5 kDa, and 10 kDa. ACE-I inhibitory activity was quantified in the hydrolysate and ultrafiltered fractions. The hydrolysate was extensive (DH = 51.64% and had 58.46% ACE-inhibitory activity. Inhibition ranged from 53.84% to 69.31% in the five ultrafiltered fractions and was highest in the <1 kDa fraction (69.31%. This fraction’s amino acid composition was identified and then it was purified by gel filtration chromatography and ACE-I inhibition measured in the purified fractions. Amino acid composition suggested that hydrophobic residues contributed substantially to chia peptide ACE-I inhibitory strength, probably by blocking angiotensin II production. Inhibitory activity ranged from 48.41% to 62.58% in the purified fractions, but fraction F1 (1.5–2.5 kDa exhibited the highest inhibition (IC50 = 3.97 μg/mL; 427–455 mL elution volume. The results point out the possibility of obtaining bioactive peptides from chia proteins by means of a controlled protein hydrolysis using Alcalase-Flavourzyme sequentional system.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Angiotensin I-Converting Enzyme Inhibitory Peptides of Chia (Salvia hispanica) Produced by Enzymatic Hydrolysis.

    Science.gov (United States)

    Segura Campos, Maira Rubi; Peralta González, Fanny; Chel Guerrero, Luis; Betancur Ancona, David

    2013-01-01

    Synthetic angiotensin I-converting enzyme (ACE-I) inhibitors can have undesirable side effects, while natural inhibitors have no side effects and are potential nutraceuticals. A protein-rich fraction from chia (Salvia hispanica L.) seed was hydrolyzed with an Alcalase-Flavourzyme sequential system and the hydrolysate ultrafiltered through four molecular weight cut-off membranes (1 kDa, 3 kDa, 5 kDa, and 10 kDa). ACE-I inhibitory activity was quantified in the hydrolysate and ultrafiltered fractions. The hydrolysate was extensive (DH = 51.64%) and had 58.46% ACE-inhibitory activity. Inhibition ranged from 53.84% to 69.31% in the five ultrafiltered fractions and was highest in the <1 kDa fraction (69.31%). This fraction's amino acid composition was identified and then it was purified by gel filtration chromatography and ACE-I inhibition measured in the purified fractions. Amino acid composition suggested that hydrophobic residues contributed substantially to chia peptide ACE-I inhibitory strength, probably by blocking angiotensin II production. Inhibitory activity ranged from 48.41% to 62.58% in the purified fractions, but fraction F1 (1.5-2.5 kDa) exhibited the highest inhibition (IC50 = 3.97 μg/mL; 427-455 mL elution volume). The results point out the possibility of obtaining bioactive peptides from chia proteins by means of a controlled protein hydrolysis using Alcalase-Flavourzyme sequentional system.

  19. Angiotensin-converting enzyme inhibition by lisinopril enhances liver regeneration in rats

    Directory of Open Access Journals (Sweden)

    F.S. Ramalho

    2001-01-01

    Full Text Available Bradykinin has been reported to act as a growth factor for fibroblasts, mesangial cells and keratinocytes. Recently, we reported that bradykinin augments liver regeneration after partial hepatectomy in rats. Angiotensin-converting enzyme (ACE is also a powerful bradykinin-degrading enzyme. We have investigated the effect of ACE inhibition by lisinopril on liver regeneration after partial hepatectomy. Adult male Wistar rats underwent 70% partial hepatectomy (PH. The animals received lisinopril at a dose of 1 mg kg body weight-1 day-1, or saline solution, intraperitoneally, for 5 days before hepatectomy, and daily after surgery. Four to six animals from the lisinopril and saline groups were sacrificed at 12, 24, 36, 48, 72, and 120 h after PH. Liver regeneration was evaluated by immunohistochemical staining for proliferating cell nuclear antigen using the PC-10 monoclonal antibody. The value for the lisinopril-treated group was three-fold above the corresponding control at 12 h after PH (P<0.001, remaining elevated at approximately two-fold above control values at 24, 36, 48 (P<0.001, and at 72 h (P<0.01 after PH, but values did not reach statistical difference at 120 h after PH. Plasma ACE activity measured by radioenzymatic assay was significantly higher in the saline group than in the lisinopril-treated group (P<0.001, with 81% ACE inhibition. The present study shows that plasma ACE inhibition enhances liver regeneration after PH in rats. Since it was reported that bradykinin also augments liver regeneration after PH, this may explain the liver growth stimulating effect of ACE inhibitors.

  20. Análise da variabilidade da freqüência cardíaca em pacientes hipertensos, antes e depois do tratamento com inibidores da enzima conversora da angiotensina II Analysis of heart rate variability in hypertensive patients before and after treatment with angiotensin II-converting enzyme inhibitors

    Directory of Open Access Journals (Sweden)

    Antônio da Silva Menezes Júnior

    2004-08-01

    Full Text Available OBJETIVO: Comparar a variabilidade de freqüência cardíaca em indivíduos normotensos e hipertensos e observar o comportamento do sistema nervoso autônomo após terapia com inibidores da enzima conversora de angiotensina II. MÉTODO: Estudados 286 pacientes com diagnóstico de hipertensão arterial, pela 1ª vez, e divididos em 4 grupos, conforme a pressão arterial diastólica (PAD: grupo A - PAD110 mmHg. Os pacientes do grupo A (normais e do grupo C (HA moderada, somando 110 e 79 pacientes, respectivamente, submeteram-se ao Holter-ECG 24h com análise de variabilidade de freqüência cardíaca no domínio do tempo (DT e no domínio da freqüência (DF. O grupo C foi tratado com inibidores da ECA durante 3 meses, e após esse período novamente avaliado com Holter-ECG 24h e variabilidade da freqüência cardíaca, e os valores comparados com os normotensos. RESULTADOS: Os parâmetros SDNN, PNN50 (DT e o espectro LF (DF foram significativamente diferentes para os dois grupos, com valores notadamente diminuídos em hipertensos (pOBJECTIVE: To compare heart rate variability in normotensive and hypertensive individuals and to observe the behavior of the autonomic nervous system after treatment with angiotensin II-converting enzyme inhibitors. METHOD: The study comprised 286 patients diagnosed with arterial hypertension (AH for the first time and divided into 4 groups according to diastolic blood pressure (DBP levels: group A - DBP110 mmHg. Group A (110 healthy individuals and group C (79 patients with moderate AH underwent 24-hour Holter-ECG with analysis of heart rate variability in time domain (TD and frequency domain (FD. The group C patients were treated with ACE inhibitors for 3 months, and, after this period, they underwent a new 24-hour Holter-ECG study for assessing heart rate variability, the values being compared with those of normotensive individuals. RESULTS: The SDNN and PNN50 parameters (TD, and the LF spectrum (FD were

  1. O uso de inibidores da enzima conversora de angiotensina e sua relação com eventos no pós-operatório de cirurgia de revascularização miocárdica The use of inhibitors of angiotensin-converting enzyme and its relation to events in the postoperative period of CABG

    Directory of Open Access Journals (Sweden)

    Graciane Radaelli

    2011-09-01

    Full Text Available FUNDAMENTO: Os inibidores da enzima conversora de angiotensina (IECA reduzem o risco de óbito, infarto agudo do miocárdio (IAM e acidente vascular encefálico (AVE em portadores de doença coronariana. No entanto, não há consenso quanto à sua indicação em pacientes que serão submetidos à cirurgia de revascularização miocárdica (CRM. OBJETIVO: Avaliar a relação entre uso pré-operatório de IECA e eventos clínicos após realização da CRM. MÉTODOS: Estudo de coorte retrospectivo. Foram incluídos dados de 3.139 pacientes consecutivos submetidos à CRM isolada em hospital terciário brasileiro, entre janeiro de 1996 e dezembro de 2009. O seguimento dos pacientes foi realizado até a alta hospitalar ou óbito. Desfechos clínicos no pós-operatório foram analisados entre os usuários e os não-usuários de IECA no pré-operatório. RESULTADOS: Cinquenta e dois por cento (1.635 dos pacientes receberam IECA no pré-operatório. O uso de IECA foi preditor independente da necessidade de suporte inotrópico (RC 1,24, IC 1,01-1,47; P=0,01, de insuficiência renal aguda (IRA, RC 1,23, IC 1,01-1,73; P=0,04 e de evolução para fibrilação atrial (FA, RC 1,32, IC 1,02-1,7; P=0,03 no pós-operatório. A mortalidade entre os pacientes que receberam ou não IECA no pré-operatório foi semelhante (10,3 vs. 9,4%, P=0,436, bem como a incidência de IAM e AVE (15,6 vs. 15,0%, P=0,694 e 3,4 vs. 3,5%, P=0,963, respectivamente. CONCLUSÃO: O uso pré-operatório de IECA foi associado a maior necessidade de suporte inotrópico e maior incidência de IRA e FA no pós-operatório, não estando associado ao aumento das taxas de IAM, AVE ou óbitoBACKGROUND: Angiotensin-converting enzyme (ACE inhibitors reduce the chance of death, myocardial infarction (MI and cerebrovascular accident (CVA in patients with coronary disease. However there is no consensus as to its indication in patients undergoing coronary artery bypass grafting (CABG. OBJECTIVE: To

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

    Directory of Open Access Journals (Sweden)

    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

  3. ANALYSIS OF ANGIOTENSIN CONVERTING ENZYME (ACE GENE INSERTION/DELETION(I/DPOLYMORPHISM IN MIGRAINE

    Directory of Open Access Journals (Sweden)

    Saime Sezer

    2013-03-01

    In patient groups DD genotype frequency was 35.0%, ID genotype frequency was 45.5% and II genotype frequency 19.5% (0.322. Allelic frequencies was detected 57.75% for D allele, 42.25% for I allele in patients. There were no significant differences in genotype/allele frequencies of angiotensin converting enzyme gene polymorphism between patients with migraine and controls (p=0.474. Our results show that I/D polymorphism of angiotensin converting enzyme gene is not a risk factor for migraine. [J Contemp Med 2013; 3(1.000: 7-11

  4. Angiotensin converting enzyme gene polymorphism in type II diabetics with nephropathy

    OpenAIRE

    Naresh, V. V. S.; Reddy, A. L. K.; Sivaramakrishna, G.; Sharma, P. V. G. K.; Vardhan, R. V.; Kumar, V. Siva

    2009-01-01

    Nephropathy is an important and a frequent complication of long-term type II diabetic nephropathy. Strong evidence exists that genetic predisposition plays a major role in the development of diabetic nephropathy. Recent studies have implicated association between angiotensin converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and nephropathy. The deletion gene polymorphism of ACE gene has been shown to be associated with increased activity of this enzyme. This study examines th...

  5. Soluble inhibitors/deactivators of cellulase enzymes from lignocellulosic biomass.

    Science.gov (United States)

    Kim, Youngmi; Ximenes, Eduardo; Mosier, Nathan S; Ladisch, Michael R

    2011-04-01

    Liquid hot water, steam explosion, and dilute acid pretreatments of lignocellulose generate soluble inhibitors which hamper enzymatic hydrolysis as well as fermentation of sugars to ethanol. Toxic and inhibitory compounds will vary with pretreatment and include soluble sugars, furan derivatives (hydroxymethyl fulfural, furfural), organic acids (acetic, formic and, levulinic acid), and phenolic compounds. Their effect is seen when an increase in the concentration of pretreated biomass in a hydrolysis slurry results in decreased cellulose conversion, even though the ratio of enzyme to cellulose is kept constant. We used lignin-free cellulose, Solka Floc, combined with mixtures of soluble components released during pretreatment of wood, to prove that the decrease in the rate and extent of cellulose hydrolysis is due to a combination of enzyme inhibition and deactivation. The causative agents were extracted from wood pretreatment liquid using PEG surfactant, activated charcoal or ethyl acetate and then desorbed, recovered, and added back to a mixture of enzyme and cellulose. At enzyme loadings of either 1 or 25mg protein/g glucan, the most inhibitory components, later identified as phenolics, decreased the rate and extent of cellulose hydrolysis by half due to both inhibition and precipitation of the enzymes. Full enzyme activity occurred when the phenols were removed. Hence detoxification of pretreated woods through phenol removal is expected to reduce enzyme loadings, and therefore reduce enzyme costs, for a given level of cellulose conversion.

  6. Angiotensin-converting enzyme gene I/D polymorphism and renal disease

    NARCIS (Netherlands)

    Navis, G; van der Kleij, FGH; de Zeeuw, D; de Jong, PE

    1999-01-01

    In recent years a vast amount of data has been published on the association between the insertion/deletion (VD) polymorphism of the gene coding for angiotensin-converting enzyme and renal disease. It has be come clear that the polymorphism does not affect the prevalence of renal disease. However, da

  7. Endothelin converting-enzyme-1 mRNA expression in human cardiovascular disease

    NARCIS (Netherlands)

    Bohnemeier, H; Pinto, YM; Horkay, F; Toth, M; Juhasz-Nagy, A; Orzechowski, HD; Bohm, M; Paul, M

    1998-01-01

    Endothelin-1 converting-enzyme (ECE-1) cleaves the precursor, big-endothelin-1, to the active peptide endothelin-1. The aim of this study was to investigate whether ECE-1 mRNA expression is modified in human cardiovascular disease. Tissue samples from the left human atrium were analyzed for ECE-1 ex

  8. Association between angiotensin-converting-enzyme gene polymorphism and failure of renoprotective therapy

    NARCIS (Netherlands)

    vanEssen, GG; Rensma, PL; deZeeuw, D; Sluiter, WJ; Scheffer, H; Apperloo, AJ; deJong, PE

    1996-01-01

    Background Polymorphism in the gene for angiotensin-converting enzyme (ACE), especially the DD genotype, is associated with risk for cardiovascular disease. Glomerulosclerosis has similarities to atherosclerosis, and we looked at ACE gene polymorphism in patients with kidney disease who were in a tr

  9. THE MECHANISM AND DIAGNOSTIC-VALUE OF ANGIOTENSIN-I CONVERTING ENZYME-INHIBITION RENOGRAPHY

    NARCIS (Netherlands)

    DEZEEUW, D; JONKER, GJ; HOVINGA, TKK; BEEKHUIS, H; PIERS, DA; HUISMAN, RM; DEJONG, PE

    1991-01-01

    The effect of angiotensin converting enzyme (ACE) inhibition on the sensitivity of radionuclide renography in the diagnosis of a unilateral renal artery stenosis was tested both in a conscious dog model and in the human situation. ACE inhibition (10 mg enalaprilic acid, intravenously) markedly impro

  10. Angiotensin converting enzyme insertion/deletion polymorphism and the risk of heart failure in hypertensive subjects.

    NARCIS (Netherlands)

    Schut, A.; Bleumink, G.S.; Stricker, B.H.C.; Hofman, A.W.I.M.; Witteman, J.C.; Pols, H.; Deckers, J.W.; Deinum, J.; Duijn, C.M. van

    2004-01-01

    AIMS: Cardiac angiotensin-I converting enzyme (ACE) activity is influenced by the ACE I/D polymorphism. Evidence suggests that the DD-genotype may be a risk factor for cardiac hypertrophy and heart failure, especially in hypertensive subjects. We assessed the relation between the ACE I/D

  11. Association between angiotensin-converting-enzyme gene polymorphism and failure of renoprotective therapy

    NARCIS (Netherlands)

    vanEssen, GG; Rensma, PL; deZeeuw, D; Sluiter, WJ; Scheffer, H; Apperloo, AJ; deJong, PE

    1996-01-01

    Background Polymorphism in the gene for angiotensin-converting enzyme (ACE), especially the DD genotype, is associated with risk for cardiovascular disease. Glomerulosclerosis has similarities to atherosclerosis, and we looked at ACE gene polymorphism in patients with kidney disease who were in a

  12. Association of I/D angiotensin-converting enzyme genotype with erythropoietin stimulation in kidney failure

    Directory of Open Access Journals (Sweden)

    Savin Marina

    2017-01-01

    Full Text Available Angiotensin-converting enzyme (ACE-gene polymorphism is a possible predisposing factor of erythropoietin response under hypoxic conditions. However, it is not completely clear whether the ACE insertion/deletion (I/D genotype has an impact on anemia in patients with permanent kidney failure. A 9-month prospective trial was conducted on 53 patients on hemodialysis aimed at determining the beneficial effect of oral vs intravenous iron in anemia management with recombinant human erythropoietin (rHuEpo, and identifying a possible association of the ACE gene I/D polymorphism with the response to rHuEpo. Patients were randomly allocated to receive 50-100 mg daily of ferrous gluconate orally (N=26 or intravenously every two weeks (N=27, together with rHuEpo-beta (200 IU/kg subcutaneously, to achieve a hemoglobin increase to 105 g/L; subsequently the rHuEpo dose was adjusted at one or two week intervals. In 34 patients who regularly received ACE-inhibitor (ACEi medication, genotyping for ACE-gene I/D polymorphism was performed using PCR, gel analysis and appropriate restriction digestion. After prolonged rHuEpo treatment, 24.5% of patients attained the targeted 9th-month hemoglobin concentration (105 g/L. Of these, 6/26 of patients received elemental iron orally and 7/27 received it intravenously. We observed an association between homozygous DD (deletion of the ACE gene and a remarkable early increase in blood hemoglobin (p=0.028, erythrocyte count (p=0.020 and hematocrit (p=0.043 after reduction of the dose of rHuEpo (F=3.95; p=0.029, irrespective of the iron repletion mode (p=0.960. This is the first report on DD genotype as a linkage marker for the optimization of rHuEpo dose for anemia management in hemodialysis patients.

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

    Science.gov (United States)

    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.

  14. Effect of angiotensin converting enzyme inhibition after acute myocardial infarction in patients with arterial hypertension. TRACE Study Group, Trandolapril Cardiac Event

    DEFF Research Database (Denmark)

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

    1997-01-01

    OBJECTIVE: To evaluate the influence of a history of arterial hypertension on the efficacy of the angiotensin converting enzyme (ACE) inhibitor trandolapril in patients with acute myocardial infarction (AMI) and left ventricular dysfunction. METHODS: A retrospective analysis of data from...... to patients with a history of arterial hypertension. ACE inhibition might be of particular importance in this group of patients but further studies to establish the clinical impact are necessary....

  15. A metal-based inhibitor of NEDD8-activating enzyme.

    Directory of Open Access Journals (Sweden)

    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.

  16. Response to angiotensin-converting enzyme inhibition is selectively blunted by high sodium in angiotensin-converting enzyme DD genotype: evidence for gene-environment interaction in healthy volunteers

    NARCIS (Netherlands)

    Lely, Anna Titia; Heerspink, H.J.L.; Zuurman, M.; Visser, F.W.; Kocks, Menno; Boomsma, F.; Navis, Ger Jan

    2010-01-01

    Background Renin-angiotensin-aldosterone system blockade is a cornerstone in cardiovascular protection. Angiotensin-converting enzyme (ACE)-DD genotype has been associated with resistance to angiotensin-converting enzyme inhibition (ACEi), but data are conflicting. As sodium intake modifies the effe

  17. Response to angiotensin-converting enzyme inhibition is selectively blunted by high sodium in angiotensin-converting enzyme DD genotype : evidence for gene-environment interaction in healthy volunteers

    NARCIS (Netherlands)

    Lely, A. Titia; Lambers Heerspink, Hiddo J.; Zuurman, Mike; Visser, Folkert W.; Kocks, Menno J. A.; Boomsma, Frans; Navis, Gerjan

    2010-01-01

    Background Renin-angiotensin-aldosterone system blockade is a cornerstone in cardiovascular protection. Angiotensin-converting enzyme (ACE)-DD genotype has been associated with resistance to angiotensin-converting enzyme inhibition (ACEi), but data are conflicting. As sodium intake modifies the effe

  18. Response to angiotensin-converting enzyme inhibition is selectively blunted by high sodium in angiotensin-converting enzyme DD genotype : Evidence for gene-environment interaction in healthy volunteers

    NARCIS (Netherlands)

    Lely, A. Titia; Lambers Heerspink, Hiddo J.; Zuurman, Mike; Visser, Folkert W.; Kocks, Menno J. A.; Boomsma, Frans; Navis, Gerjan

    2010-01-01

    Background Renin-angiotensin-aldosterone system blockade is a cornerstone in cardiovascular protection. Angiotensin-converting enzyme (ACE)-DD genotype has been associated with resistance to angiotensin-converting enzyme inhibition (ACEi), but data are conflicting. As sodium intake modifies the

  19. Encapsulation-Induced Stress Helps Saccharomyces cerevisiae Resist Convertible Lignocellulose Derived Inhibitors

    Directory of Open Access Journals (Sweden)

    Johan O. Westman

    2012-09-01

    Full Text Available The ability of macroencapsulated Saccharomyces cerevisiae CBS8066 to withstand readily and not readily in situ convertible lignocellulose-derived inhibitors was investigated in anaerobic batch cultivations. It was shown that encapsulation increased the tolerance against readily convertible furan aldehyde inhibitors and to dilute acid spruce hydrolysate, but not to organic acid inhibitors that cannot be metabolized anaerobically. Gene expression analysis showed that the protective effect arising from the encapsulation is evident also on the transcriptome level, as the expression of the stress-related genes YAP1, ATR1 and FLR1 was induced upon encapsulation. The transcript levels were increased due to encapsulation already in the medium without added inhibitors, indicating that the cells sensed low stress level arising from the encapsulation itself. We present a model, where the stress response is induced by nutrient limitation, that this helps the cells to cope with the increased stress added by a toxic medium, and that superficial cells in the capsules degrade convertible inhibitors, alleviating the inhibition for the cells deeper in the capsule.

  20. [Applications of nitrile converting enzymes in the production of fine chemicals].

    Science.gov (United States)

    Zheng, Yuguo; Xue, Yaping; Liu, Zhiqiang; Zheng, Renchao; Shen, Yinchu

    2009-12-01

    Nitriles are an important type of synthetic intermediates in the production of fine chemicals because of their easy preparations and versatile transformations. The traditional chemical conversion of nitriles to carboxylic acids and amides is feasible but it requires relatively harsh conditions of heat, acid or alkali. Nitrile converting enzymes (nitrilase, nitrile hydratase and amidase) which are used as biocatalyst for the production of fine chemicals have attracted substantial interest because of their ability to convert readily available nitriles into the corresponding higher value amides or acids under mild conditions with excellent chemo-, regio- and stereo-selectivities. Many nitrile converting enzymes have been explored and widely used for the production of fine chemicals. In this paper, various examples of biocatalytic synthesis of pharmaceuticals and their intermediates, agrochemicals and their intermediates, food and feed additives, and other fine chemicals are presented. In the near future, an increasing number of novel nitrile converting enzymes will be screened and their potential in the production of useful fine chemicals will be further exploited.

  1. Properties and applications of starch-converting enzymes of the alpha-amylase family.

    Science.gov (United States)

    van der Maarel, Marc J E C; van der Veen, Bart; Uitdehaag, Joost C M; Leemhuis, Hans; Dijkhuizen, L

    2002-03-28

    Starch is a major storage product of many economically important crops such as wheat, rice, maize, tapioca, and potato. A large-scale starch processing industry has emerged in the last century. In the past decades, we have seen a shift from the acid hydrolysis of starch to the use of starch-converting enzymes in the production of maltodextrin, modified starches, or glucose and fructose syrups. Currently, these enzymes comprise about 30% of the world's enzyme production. Besides the use in starch hydrolysis, starch-converting enzymes are also used in a number of other industrial applications, such as laundry and porcelain detergents or as anti-staling agents in baking. A number of these starch-converting enzymes belong to a single family: the alpha-amylase family or family13 glycosyl hydrolases. This group of enzymes share a number of common characteristics such as a (beta/alpha)(8) barrel structure, the hydrolysis or formation of glycosidic bonds in the alpha conformation, and a number of conserved amino acid residues in the active site. As many as 21 different reaction and product specificities are found in this family. Currently, 25 three-dimensional (3D) structures of a few members of the alpha-amylase family have been determined using protein crystallization and X-ray crystallography. These data in combination with site-directed mutagenesis studies have helped to better understand the interactions between the substrate or product molecule and the different amino acids found in and around the active site. This review illustrates the reaction and product diversity found within the alpha-amylase family, the mechanistic principles deduced from structure-function relationship structures, and the use of the enzymes of this family in industrial applications.

  2. Análisis del consumo de inhibidores de la enzima convertidora de angioténsina en el territorio oeste de La Habana, 2005-2009 Analysis of the consumption of angiotensin-converting enzyme inhibitors in the west side of Havana, 2005-2009

    Directory of Open Access Journals (Sweden)

    José Ramón Cabrera Cepero

    2011-12-01

    Full Text Available La planificación de los recursos es un problema trascendental en los países en desarrollo y también en Cuba, por lo que hacer el mejor uso de los presupuestos limitados y de las escasas divisas, es de vital importancia. Planificar las cantidades de medicamentos necesarias, para lograr garantizar una disponibilidad adecuada de estos en todos los niveles de asistencia, es una tarea en la cual intervienen un sinnúmero de factores. El objetivo de este trabajo fue demostrar en qué medida la introducción del enalapril tabletas influyó en el consumo del captopril tabletas, mediante el análisis de los patrones de consumo de los medicamentos inhibidores de la enzima convertidora de angiotensina en el territorio oeste de La Habana entre marzo de 2005 y diciembre de 2009. Para ello se realizó un estudio de utilización de medicamentos de consumo, de tipo descriptivo, observacional y retrospectivo. Se calcularon las DHD (dosis por mil habitantes día. Los resultados de este trabajo demuestran cómo en este grupo hay un desplazamiento del consumo hacia el enalapril. Este es un comportamiento lógico por la comodidad de la administración y la menor incidencia de efectos adversos. Sin embargo, el captopril se mantiene en valores entre 20 y 30 DHD x 1 000 habitantes ya que hay un grupo de pacientes que continúan con este tratamiento y es de elección en la crisis hipertensiva.The planning of resources is a pressing problem in the developing nations including Cuba, hence using restricted budgets and dwindling foreign currencies in the best possible way is a must. Planning the amount of required drugs to assure their adequate supply at all medical assistance levels is a vital task in which a number of factors are involved. This paper was aimed at showing to what extent the introduction of enalapril pills into the market influenced the consumption of captopril tablets, through the analysis of the consumption patterns of angiotensin-converting enzyme

  3. [The specific enzyme inhibitors for potential therapeutic use].

    Science.gov (United States)

    Bretner, Maria

    2015-01-01

    Therapy for hepatitis C virus (HCV) initially consisted on administering ribavirin - having a broad spectrum of action - and pegylated interferon, and was only effective in 40-50% of patients. Appropriate was to find effective inhibitors of viral replication e.g. by inhibition of a viral enzyme, NTPase/helicase required in the process of translation and RNA replication of the HCV. We developed methods of synthesis of many compounds belonging to different groups - derivatives of nucleosides, benzotriazole, benzimidazole, tropolone and epirubicine. Some of the derivatives inhibit HCV helicase activity at low concentrations and reduces replication of the viral RNA in subgenomic replicon system. In the process of HCV replication casein kinase CK2 plays an important role. It regulates the level of phosphorylation of HCV protein NS5A, which affects the production of infectious virions of HCV. Effective and selective inhibitors of kinase CK2 could be of use in the treatment of HCV in combination with other drugs. CK2 kinase phosphorylates approximately 300 proteins that affect the growth, differentiation, proliferation or apoptosis. Elevated CK2 kinase activity has been observed in several types of cancer and other diseases, therefore, inhibitors of this enzyme are potential therapeutic importance, particularly for anti-cancer treatment. Research carried out in collaboration with prof. Shugar led to the synthesis of one of the most selective inhibitors of this enzyme which is 4,5,6,7-tetrabromo-1H-benzotriazole, used for the study of the role of kinase CK2 in a number of metabolic processes in tumor cells.

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

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

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

    1990-01-01

    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...... 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...... up by the tubular cells from the peritubular capillaries since the uptake was unaffected by the acute decrease in GFR....

  6. Characterization of inhibitor(s) of β-glucuronidase enzyme activity in GUS-transgenic wheat

    KAUST Repository

    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.

  7. The role of Angiotensin-converting enzyme in blood pressure control, renal function, and male fertility.

    Science.gov (United States)

    Esther, C R; Marino, E M; Bernstein, K E

    1997-07-01

    Angiotensin-converting enzyme (ACE) is a zinc peptidase that plays a major role in the renin-angiotensin system. In mammals, the enzyme is present as two isozymes: a somatic form involved in blood-pressure regulation and a testis form of unknown function. Mice lacking ACE have been created and shown to have low systolic blood pressures and defects in renal development and function. These mice also have reduced male fertility, implicating the testis isozyme in reproductive function. (Trends Endocrinol Metab 1997;8:181-186). (c) 1997, Elsevier Science Inc.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  9. Nitrile-converting enzymes: an eco-friendly tool for industrial biocatalysis.

    Science.gov (United States)

    Ramteke, Pramod W; Maurice, Navodita G; Joseph, Babu; Wadher, Bharat J

    2013-01-01

    Nitriles are organic compounds bearing a − C ≡ N group; they are frequently known to occur naturally in both fauna and flora and are also synthesized chemically. They have wide applicability in the fields of medicine, industry, and environmental monitoring. However, the majority of nitrile compounds are considered to be lethal, mutagenic, and carcinogenic in nature and are known to cause potential health problems such as nausea, bronchial irritation, respiratory distress, convulsions, coma, and skeletal deformities in humans. Nitrile-converting enzymes, which are extracted from microorganisms, are commonly termed nitrilases and have drawn the attention of researchers all over the world to combat the toxicity of nitrile compounds. The present review focuses on the utility of nitrile-converting enzymes, sources, classification, structure, properties, and applications, as well as the future perspective on nitrilases. © 2013 International Union of Biochemistry and Molecular Biology, Inc.

  10. Activity of angiotensin-converting enzyme and risk of severe hypoglycaemia in type 1 diabetes mellitus

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, U; Agerholm-Larsen, Birgit; Pramming, S

    2001-01-01

    BACKGROUND: The insertion (I) allele of the angiotensin-converting-enzyme (ACE) gene occurs at increased frequency in endurance athletes. This association suggests that low ACE activity is favourable for performance in conditions with limited substrate availability. Such conditions occur in endur......BACKGROUND: The insertion (I) allele of the angiotensin-converting-enzyme (ACE) gene occurs at increased frequency in endurance athletes. This association suggests that low ACE activity is favourable for performance in conditions with limited substrate availability. Such conditions occur...... with those who had the II genotype. There was a significant relation between serum ACE activity and the rate of severe hypoglycaemia (relative risk per 10 U/L increment 1.4 [1.2-1.6]), corresponding to a 3.5 times higher risk for patients in the highest quartile than for those in the lowest quartile...

  11. Angiotensin-I converting enzyme inhibitory and antioxidant activities of egg protein hydrolysates produced with gastrointestinal and nongastrointestinal enzymes.

    Science.gov (United States)

    You, Sun-Jong; Wu, Jianping

    2011-08-01

    Egg is a well-known rich source of bioactive peptides. In this study, egg protein (egg white and egg yolk proteins) hydrolysates were produced with gastrointestinal enzymes (pepsin and pancreatin) or nongastrointestinal enzymes (thermolysin and alcalase), and fractionated by ultrafiltration and cation exchange chromatography. Angiotensin-I converting enzyme (ACE) inhibitory and antioxidant activities, amino acid composition and molecular weight distribution were studied, and the physicochemical properties were related with the bioactivities. Our results showed that egg protein hydrolysates produced with non-GI enzymes (thermolysin and alcalase) showed significantly higher ACE inhibitory activity, whereas similar or even lower antioxidative activities, than those of hydrolysates produced with GI enzymes. ACE-inhibitory activity significantly correlated with the amino acid composition, especially the proportion of positively charged amino acid, whereas antioxidant activities correlated with the proportion of low molecular weight peptides under 500 Da. Understanding the relationship between the bioactivities and physicochemical properties of the hydrolysates/fractions is important to facilitate the development technologies for preparing fractions with improved bioactivities. © 2011 Institute of Food Technologists®

  12. Angiotensin-Converting Enzyme Gene Polymophism in Adult Primary Focal Segmental Glomerulosclerosis

    OpenAIRE

    2014-01-01

    Background Primary focal segmental glomerulosclerosis (FSGS) accounts for a third of biopsy-proven primary glomerulonephritis in Malaysia. Pediatric studies have found the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene to be associated with renal disease progression. The aim of this study was to determine the prevalence of the ACE (I/D) genotypes in adult primary FSGS and its association with renal outcome on follow-up. Methods Prospective observational ...

  13. Relationship between changed alveolar-capillary permeability and angiotensin converting enzyme activity in serum in sarcoidosis.

    OpenAIRE

    Eklund, A; Blaschke, E

    1986-01-01

    The effect of altered alveolar-capillary permeability on angiotensin converting enzyme (ACE) activity in serum (SACE) was studied in 45 patients with sarcoidosis and 21 healthy controls. In sarcoidosis increased albumin concentrations in the bronchoalveolar lavage fluid (L albumin) and increased ratios of L albumin to albumin in serum (S albumin) indicated an increased permeability of the alveolar-capillary membrane. ACE activity in the lavage fluid (LACE) was correlated with the number of al...

  14. Early pharmacological inhibition of angiotensin-I converting enzyme activity induces obesity in adulthood

    OpenAIRE

    2015-01-01

    We have investigated early programming of body mass in order to understand the multifactorial etiology of obesity. Considering that the renin-angiotensin system (RAS) is expressed and functional in the white adipose tissue (WAT) and modulates its development, we reasoned whether early transitory inhibition of angiotensin-I converting enzyme activity after birth could modify late body mass development. Therefore, newborn Wistar rats were treated with enalapril (10 mg/kg of body mass) or saline...

  15. Angiotensin-converting enzyme gene polymorphism and middle cerebral artery stenosis in a Chinese Han population

    Institute of Scientific and Technical Information of China (English)

    Chunshu Rong; Yingqi Xing; Xinmei Jiang; Juan Wang; Baoshan Gao; Jianjun Zhao; Kangding Liu

    2013-01-01

    The angiotensin-converting enzyme gene is a candidate gene of stroke. The present study involved 62 healthy volunteers and 148 patients with middle cerebral artery stenosis as confirmed by brain color ultrasound from a Han population in North China, and determined the peripheral blood angiotensin-converting enzyme genotype using PCR-restriction fragment length polymorphism analysis. The results showed that the frequencies of the DD genotype and D allele were increased in patients with middle cerebral artery stenosis, but the difference was not statistically significant compared with healthy controls. The findings of this study on the relationship between stroke genes and middle cerebral artery stenosis indicate no significant correlation between the frequencies of the DD genotype and D allele of angiotensin-converting enzyme and middle cerebral artery stenosis in this Han population from North China. In the future, studies will be carried out to investigate correlations between multiple stroke candidate gene synergy and middle cerebral artery stenosis to provide a foundation for the development of gene therapy.

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

    DEFF Research Database (Denmark)

    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....

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

    DEFF Research Database (Denmark)

    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...... of at least one NYHA class was 2.11 (1.48-2.98, 95% CI) p classification in patients with chronic heart failure.......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 patients...... with LVSD. METHODS: Individual data from 10389 patients in NYHA classes I-IV from four large long-term studies (2-4-year follow-up) and summary data from 2302 patients in NYHA classes II-IV from 16 short-term studies (3 months follow-up) were meta-analysed to assess changes in NYHA class. RESULTS: The large...

  18. Reversible diminished renal sup(99m)Tc-DMSA uptake during converting-enzyme inhibition in a patient with renal artery stenosis

    Energy Technology Data Exchange (ETDEWEB)

    Kremer Hovinga, T.K.; Beukhof, J.R.; Donker, A.J.M.; Luyk, W.H.J. van; Piers, D.A.

    1984-03-01

    A patient is described who had accelerated hypertension and unilateral renal artery stenosis, and who developed further deterioration in renal function during treatment with captopril, an angiotension-I (AI) converting-enzyme inhibitor. sup(99m)Tc-DMSA uptake was greatly diminished in the stenotic kidney, although renal blood flow and handling of /sup 131/I hippurate was preserved. Uptake of sup(99m)Tc-DMSA in the affected kidney returned after substitution of captopril by the vasodilator minoxidil, while a comparable degree of blood pressure control was maintained. This, caution must be taken when interpreting results of sup(99m)Tc-DMSA scintigraphy in patients with proven or suspected renal artery stenosis treated with an AI converting-enzyme inhibiting drug. Moreover, our finding points to the importance of glomerular filtration in the renal handling of /sup 99/Tc-DMSA.

  19. Updated survey of the steroid-converting enzymes in human adipose tissues.

    Science.gov (United States)

    Tchernof, André; Mansour, Mohamed Fouad; Pelletier, Mélissa; Boulet, Marie-Michèle; Nadeau, Mélanie; Luu-The, Van

    2015-03-01

    Over the past decade, adipose tissues have been increasingly known for their endocrine properties, that is, their ability to secrete a number of adipocytokines that may exert local and/or systemic effects. In addition, adipose tissues have long been recognized as significant sites for steroid hormone transformation and action. We hereby provide an updated survey of the many steroid-converting enzymes that may be detected in human adipose tissues, their activities and potential roles. In addition to the now well-established role of aromatase and 11β-hydroxysteroid dehydrogenase (HSD) type 1, many enzymes have been reported in adipocyte cell lines, isolated mature cells and/or preadipocytes. These include 11β-HSD type 2, 17β-HSDs, 3β-HSD, 5α-reductases, sulfatases and glucuronosyltransferases. Some of these enzymes are postulated to bear relevance for adipose tissue physiology and perhaps for the pathophysiology of obesity. This elaborate set of steroid-converting enzymes in the cell types of adipose tissue deserves further scientific attention. Our work on 20α-HSD (AKR1C1), 3α-HSD type 3 (AKR1C2) and 17β-HSD type 5 (AKR1C3) allowed us to clarify the relevance of these enzymes for some aspects of adipose tissue function. For example, down-regulation of AKR1C2 expression in preadipocytes seems to potentiate the inhibitory action of dihydrotestosterone on adipogenesis in this model. Many additional studies are warranted to assess the impact of intra-adipose steroid hormone conversions on adipose tissue functions and chronic conditions such as obesity, diabetes and cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Design of Peptide Substrate for Sensitively and Specifically Detecting Two Aβ-Degrading Enzymes: Neprilysin and Angiotensin-Converting Enzyme

    Science.gov (United States)

    Chen, Po-Ting; Chen, Chao-Long; Lin, Lilian Tsai-Wei; Lo, Chun-Hsien; Hu, Chaur-Jong; Chen, Rita P.-Y.; Wang, Steven S.-S.

    2016-01-01

    Upregulation of neprilysin (NEP) to reduce Aβ accumulation in the brain is a promising strategy for the prevention of Alzheimer’s disease (AD). This report describes the design and synthesis of a quenched fluorogenic peptide substrate qf-Aβ(12–16)AAC (with the sequence VHHQKAAC), which has a fluorophore, Alexa-350, linked to the side-chain of its C-terminal cysteine and a quencher, Dabcyl, linked to its N-terminus. This peptide emitted strong fluorescence upon cleavage. Our results showed that qf-Aβ(12–16)AAC is more sensitive to NEP than the previously reported peptide substrates, so that concentrations of NEP as low as 0.03 nM could be detected at peptide concentration of 2 μM. Moreover, qf-Aβ(12–16)AAC had superior enzymatic specificity for both NEP and angiotensin-converting enzyme (ACE), but was inert with other Aβ-degrading enzymes. This peptide, used in conjunction with a previously reported peptide substrate qf-Aβ(1–7)C [which is sensitive to NEP and insulin-degrading enzyme (IDE)], could be used for high-throughput screening of compounds that only upregulate NEP. The experimental results of cell-based activity assays using both qf-Aβ(1–7)C and qf-Aβ(12–16)AAC as the substrates confirm that somatostatin treatment most likely upregulates IDE, but not NEP, in neuroblastoma cells. PMID:27096746

  1. Design of Peptide Substrate for Sensitively and Specifically Detecting Two Aβ-Degrading Enzymes: Neprilysin and Angiotensin-Converting Enzyme.

    Science.gov (United States)

    Chen, Po-Ting; Chen, Chao-Long; Lin, Lilian Tsai-Wei; Lo, Chun-Hsien; Hu, Chaur-Jong; Chen, Rita P-Y; Wang, Steven S-S

    2016-01-01

    Upregulation of neprilysin (NEP) to reduce Aβ accumulation in the brain is a promising strategy for the prevention of Alzheimer's disease (AD). This report describes the design and synthesis of a quenched fluorogenic peptide substrate qf-Aβ(12-16)AAC (with the sequence VHHQKAAC), which has a fluorophore, Alexa-350, linked to the side-chain of its C-terminal cysteine and a quencher, Dabcyl, linked to its N-terminus. This peptide emitted strong fluorescence upon cleavage. Our results showed that qf-Aβ(12-16)AAC is more sensitive to NEP than the previously reported peptide substrates, so that concentrations of NEP as low as 0.03 nM could be detected at peptide concentration of 2 μM. Moreover, qf-Aβ(12-16)AAC had superior enzymatic specificity for both NEP and angiotensin-converting enzyme (ACE), but was inert with other Aβ-degrading enzymes. This peptide, used in conjunction with a previously reported peptide substrate qf-Aβ(1-7)C [which is sensitive to NEP and insulin-degrading enzyme (IDE)], could be used for high-throughput screening of compounds that only upregulate NEP. The experimental results of cell-based activity assays using both qf-Aβ(1-7)C and qf-Aβ(12-16)AAC as the substrates confirm that somatostatin treatment most likely upregulates IDE, but not NEP, in neuroblastoma cells.

  2. 激素联合血管紧张素转换酶抑制剂治疗中度蛋白尿IgA肾病的随机对照研究%Corticosteroids Plus Angiotensin Converting Enzyme Inhibitor in Treating IgA Nephropathy: A Randomized Control Trial

    Institute of Scientific and Technical Information of China (English)

    熊子波; 梁伟; 王勇强; 侯霜; 张帆; 贺丽娟; 罗琼

    2012-01-01

    目的 探讨激素与血管紧张素转换酶抑制剂(ACEI)联合治疗中度蛋白尿IgA肾病患者的疗效及其影响因素.方法 选择2003年5月-2009年1月在北京大学深圳医院住院的102例IgA肾病患者,均满足血肌酐<133 μmol/L,尿蛋白为1.0 ~3.5 g/24 h.按照随机数字表分为试验组和对照组.对照组(50例)给予ACEI类药物治疗(洛汀新10 mg/d),试验组(52例)在此基础上口服泼尼松0.5 mg/kg,隔日给药,治疗12 个月,并在治疗的第1、3、5个月初分别给予甲基泼尼松龙0.5 g/d,冲击3 d.对肾脏病理改变进行分级并对各种病变进行半定量分析.结果 在0、2、4、6、8、10、12个月时两组患者平均24 h尿蛋白水平分别为:试验组(2.07±0.88)g/24 h、(0.82±0.66)g/24 h、(0.63±0.53)g/24 h、(0.56±0.51)g/24 h、(0.58±0.47)g/24 h、(0.57±0.48)g/24 h及(0.64±0.54) g/24 h;对照组(1.88±0.67)g/24 h、(1.67±0.75)g/24 h、(1.55±0.81)g/24 h、(1.24±0.77)g/24 h、(1.44±0.92)g/24 h、(1.31±0.79)g/24 h及(1.28±0.85) g/24 h,两组在治疗2个月后尿蛋白水平间差异有统计学意义(P<0.01);而试验组和对照组的血肌酐水平在治疗期间均稳定,且两组间差异无统计学意义(P>0.05).多因素分析显示激素联合ACEI治疗的疗效与肾小球硬化积分及肾小管间质积分呈负相关.结论 激素联合ACEI治疗中度蛋白尿IgA肾病,能更有效降低尿蛋白,稳定肾功能.其中影响疗效的主要因素为肾小球硬化率及肾小管间质病变程度.%Objective To evaluate the efficacy of the corticosteroids plus angiotensin converting enzyme inhibitor ( ACEI ) in treating IgA nephropathy and its influencing factors. Methods Totally 102 inpatients with IgA nephropathy hospitalized in Peking University Shenzhen Hospital were randomly enrolled. All of them met the inclusion criteria: serum creatinine a-bove 133 |j,mol/L and urine proteins 1.0 - 3. 5 g/24 h. These patients were divided into two groups: control group

  3. Relationship between response to cardiac resynchronization therapy and beta-blocker and angiotensin-converting enzyme inhibitor%心脏再同步治疗反应性与β受体阻滞剂及血管紧张素转化酶抑制剂的关系

    Institute of Scientific and Technical Information of China (English)

    高运来; 张常莹; 陆娟; 戴敏; 李库林; 郑杰; 郁志明; 王如兴

    2015-01-01

    Objective To investigate pharmacologic therapy in patients receiving cardiac resynchronization therapy (CRT)and relationship with CRT response.Methods A total of 35 patients consisting 25 males and 10 females,mean age 64.1 ± 9.7 (48-75 )years old,who underwent CRT implantation for chronic heart failure were enrolled in this study.All patients were evaluated with conventional echocardiography before and 6 months after implantation.Cardiac function class (New York Heart Association,NYHA)was also assessed according to clinical performance.Medications such as beta-blocker and angiotensin-converting enzyme inhibitor (ACEI)were analyzed before and after CRT implantation.Patients were divided into responder group and non-responder group according to response to CRT. Beta-blocker and ACEI before and after CRT implantation were compared, respectively. Relationship between doses change of beta-blocker or ACEI and response to CRT were analyzed.Results There were 28 responders and 7 non-responders. Patients of responder group received larger metoprolol succinate therapy postoperatively compared with preoperatively(average daily dose 59.6±24.4 mg/d vs 25.0±1 1.0 mg/d,P 0.05 ).Patients of responder group received larger perindopril therapy postoperatively compared with preoperatively (average daily dose 4.74±1.52 mg/d vs 3.47±0.91 mg/d,P 0.05 ). Furthermore,change of beta-blocker therapy had a good correlation with CRT response (r =0.688,P 0.05).Conclusion Response to cardiac resynchronization therapy correlated with optimal pharmacologic therapy postoperatively. Optimal pharmacologic therapy and CRT may work together to improve outcomes.%目的:分析心脏再同步治疗(CRT)患者术后药物治疗情况及与 CRT 反应性的关系。方法行 CRT 的慢性心力衰竭患者35例,平均年龄(64.1±9.7)岁;所有患者术前及术后6个月均行常规超声心动图检查,并根据临床表现评估术前及术后6个月患者心功能分级。对患者 CRT 植入

  4. Altered cardiac bradykinin metabolism in experimental diabetes caused by the variations of angiotensin-converting enzyme and other peptidases.

    Science.gov (United States)

    Adam, Albert; Leclair, Patrick; Montpas, Nicolas; Koumbadinga, Gérémy Abdull; Bachelard, Hélène; Marceau, François

    2010-04-01

    The peptidases angiotensin-converting enzyme (ACE) and neutral endopeptidase 24.11 (NEP) mediate most of the kinin catabolism in normal cardiac tissue and are the molecular targets of inhibitory drugs that favorably influence diabetic complications. We studied the variations of those kininases in the myocardium of rats in experimental diabetes. ACE and NEP activities were significantly decreased in heart membranes 4-8weeks post-streptozotocin (STZ) injection. However, insulin-dependent diabetes did not modify significantly bradykinin (BK) half-life (t(1/2)) while the effect of both ACE (enalaprilat) and ACE and NEP (omapatrilat) inhibitors on BK degradation progressively decreased, which may be explained by the upregulation of other unidentified metallopeptidase(s). In vivo insulin treatment restored the activities of both ACE and NEP. ACE and NEP activities were significantly higher in hearts of young Zucker rats than in those of Sprague-Dawley rats. BK t(1/2) and the effects of peptidase inhibitors on t(1/2) varied accordingly. It is concluded that kininase activities are subjected to large and opposite variations in rat cardiac tissue in type I and II diabetes models. A number of tissue or molecular factors may determine these variations, such as remodeling of cardiac tissue, ectoenzyme shedding to the extracellular fluid and the pathologic regulation of peptidase gene expression.

  5. The influence of Angiotensin converting enzyme and angiotensinogen gene polymorphisms on hypertrophic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Rong Luo

    Full Text Available Some studies have reported that angiotensin converting enzyme (ACE and angiotensinogen (AGT genes have been associated with hypertrophic cardiomyopathy (HCM. However, there have been inconsonant results among different studies. To clarify the influence of ACE and AGT on HCM, a systemic review and meta-analysis of case-control studies were performed. The following databases were searched to indentify related studies: PubMed database, the Embase database, the Cochrane Central Register of Controlled Trials database, China National Knowledge Information database, and Chinese Scientific and Technological Journal database. Search terms included "hypertrophic cardiomyopathy", "angiotensin converting enzyme" (ACE or "ACE" and "polymorphism or mutation". For the association of AGT M235T polymorphism and HCM, "angiotensin converting enzyme" or "ACE" was replaced with "angiotensinogen". A total of seventeen studies were included in our review. For the association of ACE I/D polymorphism and HCM, eleven literatures were included in the meta-analysis on association of penetrance and genotype. Similarly, six case-control studies were included in the meta-analysis for AGT M235T. For ACE I/D polymorphism, the comparison of DI/II genotype vs DD genotype was performed in the present meta-analysis. The OR was 0.73 (95% CI: 0.527, 0.998, P = 0.049, power = 94%, alpha = 0.05 after the study which deviated from Hardy-Weinberg Equilibrium was excluded, indicating that the ACE I/D gene polymorphism might be associated with HCM. The AGT M235T polymorphism did not significantly affect the risk of HCM. In addition, ACE I/D gene polymorphism did not significantly influence the interventricular septal thickness in HCM patients. In conclusion, the ACE I/D polymorphism might be associated with the risk of HCM.

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

    DEFF Research Database (Denmark)

    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 systemic...... vascular resistance (SVR). SVR was determined in supine and seated positions in 12 HF patients [NYHA class II-III; ejection fraction=0.29 +/- 0.03 (mean +/- SE)] and 9 control subjects. HF patients were investigated during high (n=11; withdrawal of ACE-I treatment for 24 h) and low (n=9; sustained ACE...

  7. Angiotensin-converting enzyme overexpression in myelocytes enhances the immune response.

    Science.gov (United States)

    Bernstein, Kenneth E; Gonzalez-Villalobos, Romer A; Giani, Jorge F; Shah, Kandarp; Bernstein, Ellen; Janjulia, Tea; Koronyo, Yosef; Shi, Peng D; Koronyo-Hamaoui, Maya; Fuchs, Sebastien; Shen, Xiao Z

    2014-10-01

    Angiotensin-converting enzyme (ACE) plays an important role in blood pressure control. ACE also has effects on renal function, reproduction, hematopoiesis, and several aspects of the immune response. ACE 10/10 mice overexpress ACE in monocytic cells; macrophages from ACE 10/10 mice demonstrate increased polarization toward a proinflammatory phenotype. As a result, ACE 10/10 mice have a highly effective immune response following challenge with melanoma, bacterial infection, or Alzheimer disease. As shown in ACE 10/10 mice, enhanced monocytic function greatly contributes to the ability of the immune response to defend against a wide variety of antigenic and non-antigenic challenges.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  9. Cyclophosphamide-induced changes of serum angiotensin converting enzyme activity and pulmonary microvessels ultrastructure.

    Science.gov (United States)

    Musiatowicz, B; Terlikowski, S; Sulik, M; Famulski, W; Giedrojć, J; Jakubowski, A; Sobaniec-Lotowska, M; Pasztaleniec, L; Baltaziak, M; Jabłońska, E

    1997-01-01

    The effect of cyclophosphamide (CP) on the ultrastructure of the lung tissue and the activity of angiotensin converting enzyme (ACE) in serum was evaluated in rats. The animals were given cyclophosphamide (CP) in a single intraperitoneal dose of 150 mg/kg b.w. ACE activity was evaluated in the blood serum collected from the left ventricle of the heart using the spectrophometric method. In all time subgroups, the CP-receiving animals showed a decrease in ACE activity. Ultrastructural examinations of CP-treated animals revealed increased adhesion of neutrophiles and monocytes to the damage endothelium of the alveolar septa vessels and focally accumulation of the platelets.

  10. Changes in serum angiotensin I converting enzyme activity due to carbon disulfide exposure

    Energy Technology Data Exchange (ETDEWEB)

    Filipovic, N.; Bilalbegovic, Z.; Sefic, M.; Djuric, D.

    1984-05-01

    The activity of serum angiotensin I converting enzyme (ACE) was determined in 50 workers from a viscose factory in Banja Luka, Yugoslavia, and in 50 control subjects. Activity of serum ACE was significantly lower in workers exposed to carbon disulfide than in the control group. No correlation was found between a decrease of serum ACE in exposed workers and duration of exposure. These findings indicate that the serum ACE may be influenced by carbon disulfide, but the mechanism of these changes remains to be elucidated in this case.

  11. Changes in serum angiotensin I converting enzyme activity due to carbon disulfide exposure.

    Science.gov (United States)

    Filipović, N; Bilalbegović, Z; Sefić, M; Djurić, D

    1984-01-01

    The activity of serum angiotensin I converting enzyme (ACE) was determined in 50 workers from a viscose factory in Banja Luka, Yugoslavia, and in 50 control subjects. Activity of serum ACE was significantly lower in workers exposed to carbon disulfide than in the control group. No correlation was found between a decrease of serum ACE in exposed workers and duration of exposure. These findings indicate that the serum ACE may be influenced by carbon disulfide, but the mechanism of these changes remains to be elucidated in this case.

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

    DEFF Research Database (Denmark)

    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...... were pre-fed with milks fermented using two strains of Lactobacillus helveticus . An increased response to bradykinin (10 μg/kg, intravenously injected) was observed using one of these fermented milks. It is concluded that Lactobacillus helveticus produces substances which in vivo can give rise...

  13. Screening for Enzyme Inhibitors by Surface Plasmon Resonance Combined with Mass Spectrometry

    DEFF Research Database (Denmark)

    Borch, Jonas; Roepstorff, Peter

    2004-01-01

    We have developed a novel strategy to identify enzyme inhibitors that interact directly with their enzyme targets. In the approach, an enzyme is immobilized on a sensor chip, and it is determined whether the immobilized enzyme is still active by incubation with model substrates and mass...... 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....... Furthermore, fractions of plant extracts were screened for binding to and inhibition of carboxypeptidase B....

  14. Plant Protein Inhibitors of Enzymes: Their Role in Animal Nutrition and Plant Defence.

    Science.gov (United States)

    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)

  15. Fragment-Based Screening for Enzyme Inhibitors Using Calorimetry.

    Science.gov (United States)

    Recht, Michael I; Nienaber, Vicki; Torres, Francisco E

    2016-01-01

    Isothermal titration calorimetry (ITC) provides a sensitive and accurate means by which to study the thermodynamics of binding reactions. In addition, it enables label-free measurement of enzymatic reactions. The advent of extremely sensitive microcalorimeters have made it increasingly valuable as a tool for hit validation and characterization, but its use in primary screening is hampered by requiring large quantities of reagents and long measurement times. Nanocalorimeters can overcome these limitations of conventional ITC, particularly for screening libraries of 500-1000 compounds such as those encountered in fragment-based lead discovery. This chapter describes how nanocalorimetry and conventional microcalorimetry can be used to screen compound libraries for enzyme inhibitors. © 2016 Elsevier Inc. All rights reserved.

  16. Serine proteases as candidates for proteolytic processing of angiotensin-I converting enzyme.

    Science.gov (United States)

    Aragão, Danielle S; de Andrade, Maria Claudina C; Ebihara, Fabiana; Watanabe, Ingrid K M; Magalhães, Dayane C B P; Juliano, Maria Aparecida; Hirata, Izaura Yoshico; Casarini, Dulce Elena

    2015-01-01

    Somatic angiotensin-I converting enzyme (sACE) is a broadly distributed peptidase which plays a role in blood pressure and electrolyte homeostasis by the conversion of angiotensin I into angiotensin II. N-domain isoforms (nACE) with 65 and 90 kDa have been described in body fluids, tissues and mesangial cells (MC), and a 90 kDa nACE has been described only in spontaneously hypertensive rats. The aim of this study was to investigate the existence of proteolytic enzymes that may act in the hydrolysis of sACE generating nACEs in MC. After the confirmation of the presence of ACE sheddases in Immortalized MC (IMC), we purified and characterized these enzymes using fluorogenic substrates specifically designed for ACE sheddases. Purified enzyme identified as a serine protease by N-terminal sequence was able to generate nACE. In the present study, we described for the first time the presence of ACE sheddases in IMC, identified as serine proteases able to hydrolyze sACE in vitro. Further investigations are necessary to elucidate the mechanisms responsible for the expression and regulation of ACE sheddases in MC and their roles in the generation of nACEs, especially the 90 kDa form possibly related to hypertension.

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

    DEFF Research Database (Denmark)

    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 unchanged within each treatment course but increased significantly (P less than 0.05) from the initial value to the last treatment course. Two months after cessation of treatment S-ACE returned to pretreatment values. Although the changes were modest they might mirror treatment-associated endothelial damage....

  18. The effect of angiotensin-converting enzyme inhibition throughout a superovulation protocol in ewes.

    Science.gov (United States)

    Pereira, Alécio Matos; de Souza Júnior, Antônio; Machado, Fernanda Brandão; Gonçalves, Gleisy Kelly Neves; Feitosa, Lauro César Soares; Reis, Adelina Martha; Santos, Robson Augusto Souza; Honorato-Sampaio, Kinulpe; Costa, Amilton Raposo

    2015-12-01

    Many studies identified new components of the renin–angiotensin system (RAS), such as Angiotensin-(1-7) [Ang-(1–7)] and Angiotensin-converting enzyme type 2 (ACE2), in mammalian ovaries.We previously showed Angiotensin-Converting Enzyme (ACE) inhibition, which increases the level of Ang-(1–7), stimulated ovarian estradiol output in ewe after estrous synchronization. Considering that Ang-(1–7) stimulates ovarian function and elevated estradiol before ovulation is associated with increased chance of achieving pregnancy, the present study investigated whether ACE inhibition throughout a superovulation protocol in ewe might improve ovulation outcome. At first, immunohistochemistry in ovaries of nonpregnant ewes revealed localization of Angiotensin II (Ang II), Ang-(1–7) and ACE2 in theca cells of antral follicles and in corpus luteum. Ang II and Ang-(1–7)were also detected in follicular fluid (FF) by Radioimmunoassay (RIA). Enalapril treatment throughout the superovulation protocol decreased 17β-estradiol (E2) output and raised progesterone:estradiol (P4:E2) ratio without a direct influence on ovulation and quality of embryos.

  19. A quantitative peptidomics approach to unravel immunological functions of angiotensin converting enzyme in Locusta migratoria.

    Science.gov (United States)

    Duressa, Tewodros Firdissa; Boonen, Kurt; Huybrechts, Roger

    2016-09-01

    Locusta migratoria angiotensin converting enzyme (LmACE) is encoded by multiple exons displaying variable number of genomic duplications. Treatments of lipopolysaccharide (LPS) as well as peptidoglycan but not β-1-3 glucan resulted in enhanced expression of angiotensin converting enzyme in hemocytes of Locusta migratoria. No such effect was observed in fat body cells. Differential peptidomics using locust plasma samples post infection with LPS in combination with both an LmACE transcript knockdown by RNAi and a functional knockdown using captopril allowed the identification of 5 circulating LPS induced peptides which only appear in the hemolymph of locust having full LmACE functionality. As these peptides originate from larger precursor proteins such as locust hemocyanin-like protein, having known antimicrobial properties, the obtained results suggest a possible direct or indirect role of LmACE in the release of these peptides from their precursors. Additionally, this experimental setup confirmed the role of LmACE in the clearance of multiple peptides from the hemolymph.

  20. Effect of inhibition of converting enzyme on renal hemodynamics and sodium management in polycystic kidney disease.

    Science.gov (United States)

    Torres, V E; Wilson, D M; Burnett, J C; Johnson, C M; Offord, K P

    1991-10-01

    We compared the tubular transport of sodium and the erythrocyte sodium-lithium countertransport activity in hypertensive patients with autosomal dominant polycystic kidney disease (ADPKD) and in normotensive control subjects. In addition, we assessed the effects of inhibition of converting enzyme on renal hemodynamics and sodium excretion in hypertensive patients with ADPKD to provide information on mechanisms responsible for the increased renal vascular resistance and filtration fraction and the adjustment of the pressure-natriuresis relationship during saline expansion, observed in patients with ADPKD, hypertension, and preserved renal function. In comparison with normotensive control subjects, the hypertensive patients with ADPKD had lower renal plasma flows, higher renal vascular resistances and filtration fractions, and similar proximal and distal fractional reabsorptions of sodium. The administration of enalapril resulted in significant increases in the renal plasma flow and significant reductions in mean arterial pressure, renal vascular resistance, and filtration fraction, but the glomerular filtration rate remained unchanged. Despite the significant reduction in mean arterial pressure during inhibition of converting enzyme, the distal fractional reabsorption of sodium decreased while the total fractional excretion of sodium remained unchanged or increased slightly. No significant differences were detected between the normotensive control subjects and the hypertensive patients with ADPKD in erythrocyte sodium-lithium countertransport activity, plasma renin activity, plasma aldosterone concentration, or atrial natriuretic factor. These results suggest that the renal renin-angiotensin system plays a central role in the alterations in renal hemodynamics and sodium management associated with the development of hypertension in ADPKD.

  1. Screening of marine actinobacteria for amylase enzymes inhibitors.

    Science.gov (United States)

    Raja, S; Ganesan, S; Sivakumar, K; Thangaradjou, T

    2010-06-01

    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 inhibition activity of both prokaryotic and eukaryotic amylase was tested by using Bacillus subtilis and Aspergillus niger. The maximum amylase activity (40mm) produced by the A. niger was taken as positive control, when the test actinobacteria strains grown in the medium they inhibited amylase activity and was evidenced by the reduction in inhibition zone (14-37 mm) similarly the amylase produced by the Bacillus subtilis was also recorded maximum (35 mm) amylase activity and was taken as positive control, and the test atinobacterial strains reduced enzyme action(12-33 mm) it varied levals. This indicates that the actinobacteria strains were controlled amylase enzyme activity in both the cases. The strain SSR-10 was highly effective and SSR-8 was less effective in inhibiting eukaryotic amylase produced by A. niger. The strain SSR-2 was effective and SSR-6 showed very less effect in inhibiting the prokaryotic amylase produced by the B subtilis.

  2. Dual neural endopeptidase/endothelin-converting [corrected] enzyme inhibition improves endothelial function in mesenteric resistance arteries of young spontaneously hypertensive rats

    DEFF Research Database (Denmark)

    Lemkens, Pieter; Nelissen, Jelly; Meens, Merlijn J P M T;

    2012-01-01

    through cleavage of big ET1 by endothelin-converting enzyme (ECE) and neutral endopeptidase (NEP). METHOD: We investigated whether the dual NEP/ECE inhibitor SOL1 improves resistance artery function and structure in 12 weeks old spontaneously hypertensive rats (SHRs) and whether arterial structural...... responses to decreased (-90%) or increased (+100%) blood flow are impaired in young SHRs. To this end two groups of SHRs received chronic 4-week treatment at two different time points (4-8 and 8-12 weeks) prior to the experiment. We compared in-vitro effects of cyclo-oxygenase inhibition (1 μmol...

  3. Prevalence of the angiotensin I converting enzyme insertion/deletion polymorphism, plasma angiotensin converting enzyme activity, and left ventricular mass in a normotensive Chilean population.

    Science.gov (United States)

    Jalil, J E; Piddo, A M; Cordova, S; Chamorro, G; Braun, S; Jalil, R; Vega, J; Jadue'P, L; Lavandero, S; Lastra, P

    1999-07-01

    The aim of this study was to estimate the prevalence of the different alleles of the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and associated plasma ACE activity, as well as cardiac echocardiographic structure, in a healthy Chilean population. We selected 117 healthy normotensive subjects (aged 45 to 60 years, middle socioeconomic status, nonobese, and nondiabetic) from a population-based study concerning the prevalence of risk factors for chronic diseases (Conjunto de Acciones Para la Reducción Multifactorial de las Enfermedades no Transmisibles [CARMEN]). The frequencies of the I and D alleles were 0.57 and 0.43, respectively. Mean plasma ACE activity was 15.3 +/- 3.9 U/mL. Compared with subjects with the II genotype, plasma ACE activity was significantly higher in subjects with the ID and DD genotypes with no difference between them. No correlation was observed between blood pressure and plasma ACE activity. Among the three different genotypes there was no difference in left ventricular (LV) dimensions or in LV mass. No correlation between plasma ACE activity and LV mass was observed for either gender or different genotypes. Multivariate linear regression analysis using LV mass and LV mass index as dependent variables showed independent effects (P < .05) for gender (higher LV mass in men) and diastolic blood pressure, but not for the DD genotype. In conclusion, in this population, the presence of the D allele on the ACE gene determined higher circulating ACE activity. However, in this normotensive healthy population, male gender and diastolic blood pressure, but not the presence of the D allele, were associated with increased LV mass.

  4. Mechanism of Carbamate Inactivation of FAAH: Implications for the Design of Covalent Inhibitors and In Vivo Functional Probes for Enzymes

    Science.gov (United States)

    Alexander, Jessica P.; Cravatt, Benjamin F.

    2006-01-01

    Summary Fatty acid amide hydrolase (FAAH) regulates a large class of signaling lipids, including the endocannabinoid anandamide. Carbamate inhibitors of FAAH display analgesic and anxiolytic properties in rodents. However, the mechanism by which carbamates inhibit FAAH remains obscure. Here, we provide biochemical evidence that carbamates covalently modify the active site of FAAH by adopting an orientation opposite of that originally predicted from modeling. Based on these results, a series of carbamates was designed that display enhanced potency. One agent was converted into a “click chemistry” probe to comprehensively evaluate the proteome reactivity of FAAH-directed carbamates in vivo. These inhibitors were selective for FAAH in the nervous system, but they reacted with several enzymes in peripheral tissues. The experimental strategy described herein can be used to create in vivo probes for any enzyme susceptible to covalent inhibition. PMID:16298297

  5. Urinary angiotensin-converting enzyme 2 in hypertensive patients may be increased by olmesartan, an angiotensin II receptor blocker.

    Science.gov (United States)

    Furuhashi, Masato; Moniwa, Norihito; Mita, Tomohiro; Fuseya, Takahiro; Ishimura, Shutaro; Ohno, Kohei; Shibata, Satoru; Tanaka, Marenao; Watanabe, Yuki; Akasaka, Hiroshi; Ohnishi, Hirofumi; Yoshida, Hideaki; Takizawa, Hideki; Saitoh, Shigeyuki; Ura, Nobuyuki; Shimamoto, Kazuaki; Miura, Tetsuji

    2015-01-01

    Angiotensin-converting enzyme 2 (ACE2) is highly expressed in the kidney and converts angiotensin (Ang) II to Ang-(1-7), a renoprotective peptide. Urinary ACE2 has been shown to be elevated in patients with chronic kidney disease. However, the effects of antihypertensive agents on urinary ACE2 remain unclear. Of participants in the Tanno-Sobetsu cohort study in 2011 (n = 617), subjects on no medication (n = 101) and hypertensive patients treated with antihypertensive agents, including the calcium channel blockers amlodipine and long-acting nifedipine; the ACE inhibitor enalapril; and the Ang II receptor blockers losartan, candesartan, valsartan, telmisartan, and olmesartan, for more than 1 year (n = 100) were enrolled, and urinary ACE2 level was measured. Glucose and hemoglobin A1c were significantly higher in patients treated with enalapril, telmisartan or olmesartan than in the control subjects. Urinary albumin-to-creatinine ratio (UACR) was significantly higher in patients treated with enalapril than in the control subjects. Urinary ACE2 level was higher in the olmesartan-treated group, but not the other treatment groups, than in the control group. Urinary ACE2 level was positively correlated with systolic blood pressure (r = 0.211; P = 0.003), UACR (r = 0.367; P olmesartan was an independent predictor of urinary ACE2 level. In contrast with other antihypertensive drugs, olmesartan may uniquely increase urinary ACE2 level, which could potentially offer additional renoprotective effects. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Interleukin-1 beta converting enzyme requires oligomerization for activity of processed forms in vivo.

    Science.gov (United States)

    Gu, Y; Wu, J; Faucheu, C; Lalanne, J L; Diu, A; Livingston, D J; Su, M S

    1995-05-01

    Interleukin-1 beta converting enzyme (ICE) is composed of 10' (p10) and 20 kDa (p20) subunits, which are derived from a common 45 kDa precursor. Recent crystallographic studies have shown that ICE exists as a tetramer (p20/p10)2 in the crystal lattice. We provide evidence that the p10 and p20 subunits of ICE associate as oligomers in transfected COS cells. Using intragenic complementation, we show that the activity of a p10/p10 interface mutant defective in autoprocessing can be restored by co-expression with active site ICE mutants. Different active site mutants can also complement each other by oligomerization to form active ICE. These studies indicate that ICE precursor polypeptides may associate in different quaternary structures and that oligomerization is required for autoprocessing. Furthermore, integenic complementation of active site mutants of ICE and an ICE homolog restores autoprocessing activity, suggesting that hetero-oligomerization occurs between ICE homologs.

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

    Institute of Scientific and Technical Information of China (English)

    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 ionizable 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.

  8. Effect of bilirubin on the spectrophotometric and radionuclide assay for serum angiotensin-converting enzyme

    Energy Technology Data Exchange (ETDEWEB)

    Saxe, A.W.; Hollinger, M.A.; Essam, T.

    1986-01-01

    The effect of bilirubin on serum angiotensin-converting enzyme (ACE) activity was studied with spectrophotometric and radionuclide assays. In the spectrophotometric assay addition of bilirubin to normal serum from dog, mouse, and human produced a dose-related inhibition of ACE activity. A 50% decrease in human ACE activity was produced by the addition of approximately 250 mg/L in vitro. Serum from icteric patients with elevated bilirubin was also associated with a reduction in ACE activity in the spectrophotometric assay. A 50% decrease in ACE activity in these samples was associated with a serum bilirubin of approximately 220 mg/L. In the radionuclide assay, however, addition of bilirubin to normal human serum failed to reduce measured ACE activity. The use of a radionuclide assay for serum ACE in clinical samples offers the advantage of less interference from serum bilirubin.

  9. Nandrolone increases angiotensin-I converting enzyme activity in rats tendons

    Directory of Open Access Journals (Sweden)

    Rita de Cassia Marqueti

    2015-06-01

    Full Text Available INTRODUCTION: The renin-angiotensin system (RAS has been associated with several biological processes of the human body, regulating, among others blood pressure and water and electrolytes balance. Moreover, RAS also regulates connective tissue growth. Recently, studies have shown that the use of nandrolone modifies the angiotensin-I converting enzyme (ACE activity and increases collagen deposition in the heart. OBJECTIVE: The aim of study was to evaluate the Angiotensin-I converting enzyme (ACE activity in the superficial flexor tendon (SFT and in serum after load exercise in combination with anabolic androgenic steroid (AAS administration after training session and six weeks of detraining. METHODS: Forty-eight Wistar rats were used into two groups (G1 and G2 subdivided into four subgroups: Sedentary (S; trained (T; AAS-treated (Deca-Durabolin(r, 5mg/kg, twice a week sedentary rats (AAS and AAS-treated and trained animals (AAST. Trained groups performed jumps in water: four series of 10 jumps each, followed by a 30 sec interval between the series, for seven weeks. RESULTS: Training increased ACE activity in the SFT compared to the control group (p <0.05. Both AAS and AAST groups presented higher ACE activity levels (p < 0.05. The AAST increased the ACE activity only compared to the trained animals. Only the AAST group presented significant higher levels of ACE in the serum. In the G2 group, all experimental groups presented decreased ACE activity in the serum and in the tendon, as compared to the control group. CONCLUSION: This study indicates that AAS administration and its combination with exercise increased ACE activity of tendons. AAS abuse could compromise tendon adaptation causing maladaptive remodeling.

  10. Empirical and bioinformatic characterization of buffalo (Bubalus bubalis) colostrum whey peptides & their angiotensin I-converting enzyme inhibition.

    Science.gov (United States)

    Ashok, N R; Aparna, H S

    2017-08-01

    Whey based peptides are well known for their nutritional and multifunctional properties. In this context, whey proteins from buffalo colostrum & milk were digested by in vitro simulation digestion and analyzed by nano-LC-MS/MS. Functional protein association networks, gene annotations and localization of identified proteins were carried out. An ACE inhibitory peptide sorted from the library was custom synthesized and an in vitro ACE assay was performed. The study led to the identification of 74 small peptides which were clustered into 5 gene functional groups and majority of them were secretory proteins. Among the identified peptides, majority of them were found identical to angiotensin I-converting enzyme (ACE) inhibitors, antioxidant, antimicrobial, immunomodulatory and opioidal peptides. An octapeptide (m/z - 902.51, IQKVAGTW) synthesized was found to inhibit ACE with an IC50 of 300±2µM. The present investigation thus establishes newer vista for food derived peptides having ACE inhibitory potential for nutraceutical or therapeutic applications.

  11. Behavioural changes induced by angiotensin-converting enzyme inhibition during pregnancy and lactation in adult offspring rats.

    Science.gov (United States)

    Mecawi, A S; Araujo, I G; Fonseca, F V; Almeida-Pereira, G; Côrtes, W S; Rocha, F F; Reis, L C

    2009-05-01

    1. The use of angiotensin-converting enzyme (ACE) inhibitors during pregnancy is contraindicated because of their association with increased risks of fetopathy, including central nervous systems malformations. In addition, some reports have shown that renin-angiotensin system components are expressed differently during embryonic development and adulthood in the rat. 2. Because angiotensin II and its derivative peptides have been implicated in anxiety and modulation of nociception, the aim of the present study was to investigate whether inhibiting ACE during prenatal and neonatal periods would alter behavioural plasticity in adult male offspring rats. 3. Female Wistar rats were treated with captopril (2 mg/mL water; approximately 200 mg/kg per day) during pregnancy and lactation. At adulthood, the offspring were subjected to the open field, elevated plus maze, social interaction, forced swimming and tail flick tests. 4. Perinatal captopril treatment significantly increased ambulation (33%; P swimming test, there was an increased latency period (102.9%; P < 0.001) and a decreased immobility period (38.7, P < 0.05) in rats treated with perinatal captopril. In the tail flick test, perinatal captopril treatment significantly reduced the latency time (26.3%; P < 0.01). 5. The data show that ACE inhibition during prenatal and neonatal periods affects behavioural responses in adult offspring rats, suggesting that ACE is required for the development of neural systems that are associated with adult anxiety and nociceptive behavioural responses.

  12. The effectiveness and safety of angiotensin-converting enzyme inhibition or receptor blockade in vascular diseases in patients with hemodialysis

    Science.gov (United States)

    Liao, Kuang-Ming; Cheng, Hui-Teng; Lee, Yi-Hsuan; Chen, Chung-Yu

    2017-01-01

    Abstract Patients with end-stage renal disease (ESRD) who are on hemodialysis have high risk of vascular diseases. Our study sought to examine whether angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin type 1 receptor blockers (ARBs) could reduce the frequencies of cardiovascular and cerebrovascular events in patients receiving hemodialysis using the medication possession ratio (MPR) method of analysis. This retrospective cohort study identified cases of ESRD with dialysis from the National Health Insurance Research Database between 1999 and 2006, and used Cox-regression methods to evaluate risk of poor outcomes. Primary outcomes, including death from any cause, and secondary outcomes, including admission for stroke, myocardial infarction, and heart failure, were examined. Compared to the nonuser group, the adjusted HRs for mortality of the nonadherence group and the adherence group were 0.81 (95% CI: 0.76–0.86) and 0.98 (95% CI: 0.86–1.13), respectively. Cardiovascular events were more frequent in patients with ESRD receiving ACEIs /ARBs than in nonusers. Compared with nonusers, the hazard of secondary outcome significantly increased in the nonadherence group or adherence group in 10 years follow-up. Compared with patients with diabetes or chronic kidney disease, patients on hemodialysis may not experience the same cardiovascular and cerebrovascular benefits from ACEIs/ARBs use. PMID:28353612

  13. Identification of Angiotensin I-Converting Enzyme Inhibitory Peptides Derived from Enzymatic Hydrolysates of Razor Clam Sinonovacula constricta

    Directory of Open Access Journals (Sweden)

    Yun Li

    2016-06-01

    Full Text Available Angiotensin I-converting enzyme (ACE inhibitory activity of razor clam hydrolysates produced using five proteases, namely, pepsin, trypsin, alcalase, flavourzyme and proteases from Actinomucor elegans T3 was investigated. Flavourzyme hydrolysate showed the highest level of degree of hydrolysis (DH (45.87% followed by A. elegans T3 proteases hydrolysate (37.84% and alcalase (30.55%. The A. elegans T3 proteases was observed to be more effective in generating small peptides with ACE-inhibitory activity. The 3 kDa membrane permeate of A. elegans T3 proteases hydrolysate showed the highest ACE-inhibitory activity with an IC50 of 0.79 mg/mL. After chromatographic separation by Sephadex G-15 gel filtration and reverse phase-high performance liquid chromatography, the potent fraction was subjected to MALDI/TOF-TOF MS/MS for identification. A novel ACE-inhibitory peptide (VQY was identified exhibiting an IC50 of 9.8 μM. The inhibitory kinetics investigation by Lineweaver-Burk plots demonstrated that the peptide acts as a competitive ACE inhibitor. The razor clam hydrolysate obtained by A. elegans T3 proteases could serve as a source of functional peptides with ACE-inhibitory activity for physiological benefits.

  14. A continuous fluorescent assay for the determination of plasma and tissue angiotensin I-converting enzyme activity

    Directory of Open Access Journals (Sweden)

    M.F. Alves

    2005-06-01

    Full Text Available A continuous assay using internally quenched fluorescent peptides with the general sequence Abz-peptidyl-(DnpP-OH (Abz = ortho-aminobenzoic acid; Dnp = 2,4-dinitrophenyl was optimized for the measurement of angiotensin I-converting enzyme (ACE in human plasma and rat tissues. Abz-FRK(DnpP-OH, which was cleaved at the Arg-Lys bond by ACE, was used for the enzyme evaluation in human plasma. Enzymatic activity was monitored by continuous recording of the fluorescence (lambdaex = 320 nm and lambdaem = 420 nm at 37ºC, in 0.1 M Tris-HCl buffer, pH 7.0, with 50 mM NaCl and 10 µM ZnCl2. The assays can be performed directly in the cuvette of the fluorimeter and the hydrolysis followed for 5 to 10 min. ACE measurements in the plasma of 80 healthy patients with Hip-His-Leu and with Abz-FRK(DnpP-OH correlated closely (r = 0.90, P < 0.001. The specificity of the assay was demonstrated by the complete inhibition of hydrolysis by 0.5 µM lisinopril or captopril. Abz-FRK(DnpP-OH cleavage by ACE was monitored in rat lung, kidney, heart, and liver homogenates in the presence of a cocktail of inhibitors containing trans-epoxy-succinyl-L-leucylamido-(4-guanido-butene, pepstatin, phenyl-methylsulfonyl fluoride, N-tosyl-L-phenylalanyl-chloromethyl ketone, and N-tosyl-lysyl-chloromethyl ketone to prevent undesirable hydrolysis. ACE activity in lung, heart and kidney homogenates, but not in liver homogenates, was completely abolished by 0.5 µM lisinopril or captopril. The advantages of the method are the procedural simplicity and the high sensitivity providing a rapid assay for ACE determinations.

  15. Molecular diversity of tuliposide A-converting enzyme in the tulip.

    Science.gov (United States)

    Nomura, Taiji; Tsuchigami, Aya; Ogita, Shinjiro; Kato, Yasuo

    2013-01-01

    Tuliposide A-converting enzyme (TCEA) catalyzes the conversion of 6-tuliposide A to its lactonized aglycon, tulipalin A, in the tulip (Tulipa gesneriana). The TgTCEA gene, isolated previously from petals, was transcribed in all tulip tissues but not in the bulbs despite the presence of TCEA activity, which allowed prediction of the presence of a TgTCEA isozyme gene preferentially expressed in the bulbs. Here, the TgTCEA-b gene, the TgTCEA homolog, was identified in bulbs. TgTCEA-b polypeptides showed approximately 77% identity to the petal TgTCEA. Functional characterization of the recombinant enzyme verified that TgTCEA-b encoded the TCEA. Moreover, the TgTCEA-b was found to be localized to plastids, as found for the petal TgTCEA. Transcript analysis revealed that TgTCEA-b was functionally transcribed in the bulb scales, unlike the TgTCEA gene, whose transcripts were absent there. In contrast, TgTCEA-b transcripts were in the minority in other tissues where TgTCEA transcripts were dominant, indicating a tissue preference for the transcription of those isozyme genes.

  16. Systemic overexpression of TNFα-converting enzyme does not lead to enhanced shedding activity in vivo.

    Directory of Open Access Journals (Sweden)

    Masaki Yoda

    Full Text Available TNFα-converting enzyme (TACE/ADAM17 is a membrane-bound proteolytic enzyme with a diverse set of target molecules. Most importantly, TACE is indispensable for the release and activation of pro-TNFα and the ligands for epidermal growth factor receptor in vivo. Previous studies suggested that the overproduction of TACE is causally related to the pathogenesis of inflammatory diseases and cancers. To test this hypothesis, we generated a transgenic line in which the transcription of exogenous Tace is driven by a CAG promoter. The Tace-transgenic mice were viable and exhibited no overt defects, and the quantitative RT-PCR and Western blot analyses confirmed that the transgenically introduced Tace gene was highly expressed in all of the tissues examined. The Tace-transgenic mice were further crossed with Tace⁻/⁺ mice to abrogate the endogenous TACE expression, and the Tace-transgenic mice lacking endogenous Tace gene were also viable without any apparent defects. Furthermore, there was no difference in the serum TNFα levels after lipopolysaccharide injection between the transgenic mice and control littermates. These observations indicate that TACE activity is not necessarily dependent on transcriptional regulation and that excess TACE does not necessarily result in aberrant proteolytic activity in vivo.

  17. Association of angiotensin-converting enzyme, CYP46A1 genes polymorphism with senile cataract

    Science.gov (United States)

    Raza, Syed Tasleem; Abbas, Shania; Chandra, Anu; Singh, Luxmi; Rizvi, Saliha; Mahdi, Farzana

    2017-01-01

    Background: Senile cataract is the most common type of cataract characterized by gradual progressive thickening of the lens of the eye. Previously, many studies investigated the association between genetic polymorphism and senile cataract. Angiotensin-converting enzyme (ACE) I/D polymorphism is the potential risk factor for many eye-related diseases such as retinopathy and glaucoma. CYP46A1 enzyme converts cholesterol to 24S-hydroxycholesterol; human lens' membranes contain the highest cholesterol content. Defects in enzymes of cholesterol metabolism can be associated with cataracts. Hence, the present study was carried out to investigate the association of ACE and CYP46A1 genes polymorphism with senile cataract cases and controls. Materials and Methods: ACE (rs 4646994) and CYP46A1 (rs 754203) genes polymorphism in cases and controls were evaluated by polymerase chain reaction and restriction fragment length polymorphism. Results: This study included 103 senile cataract cases (55 were males and 48 were females) and 102 controls (53 were males and 49 were females). Mean age of cases in this study was 52.02 ± 12.11 years while in control group 53.74 ± 11.87 years. Frequencies of ACE ID, DD, and II genotypes in senile cataract cases were 64.07%, 4.85%, and 31.06% and controls were 61.76%, 26.47%, and 11.76%, respectively. The CYP46A1 gene CT, CC, and TT genotype frequencies were 48.54%, 8.73%, and 42.71% in senile cataract cases and 28.43%, 3.92%, and 67.64% in healthy controls, respectively. ACE DD and II genotypes (P < 0.001,P = 0.0008) and CYP46A1 CT and TT genotypes (P = 0.003,P = 0.0003) were significantly associated with senile cataract cases compared to the controls. Conclusion: Findings of this study suggest that ACE and CYP46A1 genes polymorphism may be a predictive marker for early identification of population at risk of senile cataract. This potential role of ACE and CYP46A1 genes polymorphism as a marker of susceptibility to senile cataract needs

  18. Simplified assays of lipolysis enzymes for drug discovery and specificity assessment of known inhibitors.

    Science.gov (United States)

    Iglesias, Jose; Lamontagne, Julien; Erb, Heidi; Gezzar, Sari; Zhao, Shangang; Joly, Erik; Truong, Vouy Linh; Skorey, Kathryn; Crane, Sheldon; Madiraju, S R Murthy; Prentki, Marc

    2016-01-01

    Lipids are used as cellular building blocks and condensed energy stores and also act as signaling molecules. The glycerolipid/ fatty acid cycle, encompassing lipolysis and lipogenesis, generates many lipid signals. Reliable procedures are not available for measuring activities of several lipolytic enzymes for the purposes of drug screening, and this resulted in questionable selectivity of various known lipase inhibitors. We now describe simple assays for lipolytic enzymes, including adipose triglyceride lipase (ATGL), hormone sensitive lipase (HSL), sn-1-diacylglycerol lipase (DAGL), monoacylglycerol lipase, α/β-hydrolase domain 6, and carboxylesterase 1 (CES1) using recombinant human and mouse enzymes either in cell extracts or using purified enzymes. We observed that many of the reported inhibitors lack specificity. Thus, Cay10499 (HSL inhibitor) and RHC20867 (DAGL inhibitor) also inhibit other lipases. Marked differences in the inhibitor sensitivities of human ATGL and HSL compared with the corresponding mouse enzymes was noticed. Thus, ATGListatin inhibited mouse ATGL but not human ATGL, and the HSL inhibitors WWL11 and Compound 13f were effective against mouse enzyme but much less potent against human enzyme. Many of these lipase inhibitors also inhibited human CES1. Results describe reliable assays for measuring lipase activities that are amenable for drug screening and also caution about the specificity of the many earlier described lipase inhibitors.

  19. Computational optimization of AG18051 inhibitor for amyloid-beta binding alcohol dehydrogenase enzyme

    Science.gov (United States)

    Marques, Alexandra T.; Antunes, Agostinho; Fernandes, Pedro A.; Ramos, Maria J.

    Amyloid-beta (Abeta) binding alcohol dehydrogenase (ABAD) is a multifunctional enzyme involved in maintaining the homeostasis. The enzyme can also mediate some diseases, including genetic diseases, Alzheimer's disease, and possibly some prostate cancers. Potent inhibitors of ABAD might facilitate a better clarification of the functions of the enzyme under normal and pathogenic conditions and might also be used for therapeutic intervention in disease conditions mediated by the enzyme. The AG18051 is the only presently available inhibitor of ABAD. It binds in the active-site cavity of the enzyme and reacts with the NAD+ cofactor to form a covalent adduct. In this work, we use computational methods to perform a rational optimization of the AG18051 inhibitor, through the introduction of chemical substitutions directed to improve the affinity of the inhibitor to the enzyme. The molecular mechanics-Poisson-Boltzmann surface area methodology was used to predict the relative free binding energy of the different modified inhibitor-NAD-enzyme complexes. We show that it is possible to increase significantly the affinity of the inhibitor to the enzyme with small modifications, without changing the overall structure and ADME (absorption, distribution, metabolism, and excretion) properties of the original inhibitor.

  20. Rabbit pulmonary angiotensin-converting enzyme: the NH2-terminal fragment with enzymatic activity and its formation from the native enzyme by NH4OH treatment.

    Science.gov (United States)

    Iwata, K; Blacher, R; Soffer, R L; Lai, C Y

    1983-11-01

    The NH2-terminal sequence of 22 residues of rabbit lung angiotensin-converting enzyme has been determined as (NH2)Thr-Leu-Asp-Pro-Gly-Leu-Leu-Pro-Gly-Asp-Phe-Ala -Ala-Asp-Asn-Ala-Gly-Ala-Arg-Leu-Phe-Ala-. In the course of purification of the enzyme for structural analysis a protein of Mr = 82,000 with angiotensin-converting activity was separated from the major fraction containing the native enzyme (Mr = 140,000). This low-molecular-weight enzyme catalyzed the hydrolysis of the synthetic substrate Hip-His-Leu at a rate 23% of that with the native enzyme, and exhibited a similar Km value as well as behaviors towards various effectors of angiotensin-converting enzyme. Edman degradation of both the native and the 82K enzymes revealed that they contain identical amino acid sequences from the NH2-termini. This result and those of peptide mapping and carbohydrate and amino acid analyses indicate that the 82K enzyme is a fragment derived from the NH2-terminal portion of the native enzyme, and hence contains its catalytic site. Evidence has been obtained indicating that the active fragment was formed from the native enzyme during its elution from the antibody-affinity column with NH4OH: on treatment of the native enzyme (140K Mr) with 1 N NH4OH at room temperature, a cleavage occurred and two proteins with Mr = 82K and Mr = 62K were obtained. The 82K Mr fragment was found to be enzymatically active and to contain the same NH2-terminal sequence as the native enzyme. The other fragment (62K Mr) was devoid of the activity and was shown to derive from the COOH-terminal portion of the native enzyme by the peptide mapping and terminal analyses. Cleavage of a peptide bond with NH4OH is unusual and appears to be specific for the native angiotensin-converting enzyme from rabbit lung.

  1. Angiotensin-(1-12) requires angiotensin converting enzyme and AT1 receptors for cardiovascular actions within the solitary tract nucleus.

    Science.gov (United States)

    Arnold, Amy C; Isa, Katsunori; Shaltout, Hossam A; Nautiyal, Manisha; Ferrario, Carlos M; Chappell, Mark C; Diz, Debra I

    2010-09-01

    The novel peptide, angiotensin (ANG)-(1-12), elicits a systemic pressor response and vasoconstriction. These effects are blocked by ANG converting enzyme (ACE) inhibitors or AT(1) receptor antagonists, suggesting a role as an ANG II precursor. However, ANG-(1-12) can serve as a substrate for either ANG II or ANG-(1-7) formation, depending on the local tissue enzymes. Although levels of ANG-(1-12) are higher than ANG I or ANG II in brain, the role and processing of this peptide for autonomic control of heart rate (HR) has yet to be considered. Thus we examined the effects of nucleus tractus solitarii (NTS) microinjection of ANG-(1-12) on baroreflex sensitivity for control of HR, resting arterial pressure (AP) and HR, and indexes of sympathovagal balance in urethane/chloralose anesthetized Sprague-Dawley rats. NTS injection of ANG-(1-12) (144 fmol/120 nl) significantly impaired the evoked baroreflex sensitivity to increases in AP [n = 7; 1.06 +/- 0.06 baseline vs. 0.44 +/- 0.07 ms/mmHg after ANG-(1-12)], reduced the vagal component of spontaneous baroreflex sensitivity and HR variability, and elicited a transient depressor response (P < 0.05). NTS pretreatment with an AT(1) receptor antagonist or ACE inhibitor prevented ANG-(1-12)-mediated autonomic and depressor responses. ANG-(1-12) immunostaining was observed in cells within the NTS of Sprague-Dawley rats, providing a potential intracellular source for the peptide. However, acute NTS injection of an ANG-(1-12) antibody did not alter resting baroreflex sensitivity, AP, or HR in these animals. Collectively, these findings suggest that exogenous ANG-(1-12) is processed to ANG II for cardiovascular actions at AT(1) receptors within the NTS. The lack of acute endogenous ANG-(1-12) tone for cardiovascular regulation in Sprague-Dawley rats contrasts with chronic immunoneutralization in hypertensive rats, suggesting that ANG-(1-12) may be activated only under hypertensive conditions.

  2. Angiotensin-(1–12) requires angiotensin converting enzyme and AT1 receptors for cardiovascular actions within the solitary tract nucleus

    Science.gov (United States)

    Arnold, Amy C.; Isa, Katsunori; Shaltout, Hossam A.; Nautiyal, Manisha; Ferrario, Carlos M.; Chappell, Mark C.

    2010-01-01

    The novel peptide, angiotensin (ANG)-(1–12), elicits a systemic pressor response and vasoconstriction. These effects are blocked by ANG converting enzyme (ACE) inhibitors or AT1 receptor antagonists, suggesting a role as an ANG II precursor. However, ANG-(1–12) can serve as a substrate for either ANG II or ANG-(1–7) formation, depending on the local tissue enzymes. Although levels of ANG-(1–12) are higher than ANG I or ANG II in brain, the role and processing of this peptide for autonomic control of heart rate (HR) has yet to be considered. Thus we examined the effects of nucleus tractus solitarii (NTS) microinjection of ANG-(1–12) on baroreflex sensitivity for control of HR, resting arterial pressure (AP) and HR, and indexes of sympathovagal balance in urethane/chloralose anesthetized Sprague-Dawley rats. NTS injection of ANG-(1–12) (144 fmol/120 nl) significantly impaired the evoked baroreflex sensitivity to increases in AP [n = 7; 1.06 ± 0.06 baseline vs. 0.44 ± 0.07 ms/mmHg after ANG-(1–12)], reduced the vagal component of spontaneous baroreflex sensitivity and HR variability, and elicited a transient depressor response (P < 0.05). NTS pretreatment with an AT1 receptor antagonist or ACE inhibitor prevented ANG-(1–12)-mediated autonomic and depressor responses. ANG-(1–12) immunostaining was observed in cells within the NTS of Sprague-Dawley rats, providing a potential intracellular source for the peptide. However, acute NTS injection of an ANG-(1–12) antibody did not alter resting baroreflex sensitivity, AP, or HR in these animals. Collectively, these findings suggest that exogenous ANG-(1–12) is processed to ANG II for cardiovascular actions at AT1 receptors within the NTS. The lack of acute endogenous ANG-(1–12) tone for cardiovascular regulation in Sprague-Dawley rats contrasts with chronic immunoneutralization in hypertensive rats, suggesting that ANG-(1–12) may be activated only under hypertensive conditions. PMID:20562338

  3. Evolution toward small molecule inhibitor resistance affects native enzyme function and stability, generating acarbose-insensitive cyclodextrin glucanotransferase variants

    NARCIS (Netherlands)

    Kelly, Ronan M.; Leemhuis, Hans; Gatjen, Linda; Dijkhuizen, Lubbert; Gätjen, Linda

    2008-01-01

    Small molecule inhibitors play an essential role in the selective inhibition of enzymes associated with human infection and metabolic disorders. Targeted enzymes may evolve toward inhibitor resistance through selective incorporation of mutations. Acquisition of insensitivity may, however, result in

  4. Evolution toward small molecule inhibitor resistance affects native enzyme function and stability, generating acarbose-insensitive cyclodextrin glucanotransferase variants

    NARCIS (Netherlands)

    Kelly, Ronan M.; Leemhuis, Hans; Gatjen, Linda; Dijkhuizen, Lubbert; Gätjen, Linda

    2008-01-01

    Small molecule inhibitors play an essential role in the selective inhibition of enzymes associated with human infection and metabolic disorders. Targeted enzymes may evolve toward inhibitor resistance through selective incorporation of mutations. Acquisition of insensitivity may, however, result in

  5. Functional analysis of the human somatic angiotensin I-converting enzyme gene promoter.

    Science.gov (United States)

    Testut, P; Soubrier, F; Corvol, P; Hubert, C

    1993-08-01

    Angiotensin I-converting enzyme (ACE) is a key enzyme in the regulation of systemic blood pressure and plays a major role in the renin-angiotensin and bradykinin-kinin systems, at the luminal surface of the vascular endothelia. To identify the promoter region, the transcription regulatory elements and the cell specificity of the ACE gene, five successive DNA deletions of the 5' upstream region (-1214, -754, -472, -343, -132 bp relative to the start site of transcription) were isolated and fused in sense and antisense orientations to the bacterial chloramphenicol acetyltransferase (CAT) reporter gene in the promoterless plasmid pBLCAT3. Promoter activities were measured in transient transfection assays using three different cell lines from rabbit endothelium (RE), human embryocarcinoma (Tera-1) and hepatocarcinoma cells (HepG2). All five fragments of the ACE promoter region directed expression of the CAT gene when transfected into the endothelial and the embryocarcinoma cells, which contain endogenous ACE mRNA and express ACE activity. In contrast only minimal levels of promoter activity were obtained on transfection into hepatocarcinoma cells in which endogenous ACE mRNA and ACE activity were not detected. Transfection of RE and Tera-1 cells demonstrated that promoter activity was defined by the length of the ACE promoter sequence inserted into the construct. The 132 bases located upstream from the transcription start site were sufficient to confer ACE promoter activity, whereas the sequences upstream from -472 bp and between -343 bp and -132 bp were responsible for a decrease of promoter activity. Furthermore, the minimal 132 bp of the ACE promoter contains elements which direct cell-specific CAT expression. In addition, the DNA transfection study in the presence of dexamethasone suggested that the potential glucocorticoid regulatory elements, located in the sequence of the ACE promoter, are not functional.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Characterization of two Streptomyces enzymes that convert ferulic acid to vanillin.

    Science.gov (United States)

    Yang, Wenwen; Tang, Hongzhi; Ni, Jun; Wu, Qiulin; Hua, Dongliang; Tao, Fei; Xu, Ping

    2013-01-01

    Production of flavors from natural substrates by microbial transformation has become a growing and expanding field of study over the past decades. Vanillin, a major component of vanilla flavor, is a principal flavoring compound used worldwide. Streptomyces sp. strain V-1 is known to be one of the most promising microbial producers of natural vanillin from ferulic acid. Although identification of the microbial genes involved in the biotransformation of ferulic acid to vanillin has been previously reported, purification and detailed characterization of the corresponding enzymes with important functions have rarely been studied. In this study, we isolated and identified 2 critical genes, fcs and ech, encoding feruloyl-CoA synthetase and enoyl-CoA hydratase/aldolase, respectively, which are involved in the vanillin production from ferulic acid. Both genes were heterologously expressed in Escherichia coli, and the resting cell reactions for converting ferulic acid to vanillin were performed. The corresponding crucial enzymes, Fcs and Ech, were purified for the first time and the enzymatic activity of each purified protein was studied. Furthermore, Fcs was comprehensively characterized, at an optimal pH of 7.0 and temperature of 30°C. Kinetic constants for Fcs revealed the apparent Km, kcat, and Vmax values to be 0.35 mM, 67.7 s(-1), and 78.2 U mg(-1), respectively. The catalytic efficiency (kcat/Km) value of Fcs was 193.4 mM(-1) s(-1) for ferulic acid. The characterization of Fcs and Ech may be helpful for further research in the field of enzymatic engineering and metabolic regulation.

  8. Characterization of two Streptomyces enzymes that convert ferulic acid to vanillin.

    Directory of Open Access Journals (Sweden)

    Wenwen Yang

    Full Text Available Production of flavors from natural substrates by microbial transformation has become a growing and expanding field of study over the past decades. Vanillin, a major component of vanilla flavor, is a principal flavoring compound used worldwide. Streptomyces sp. strain V-1 is known to be one of the most promising microbial producers of natural vanillin from ferulic acid. Although identification of the microbial genes involved in the biotransformation of ferulic acid to vanillin has been previously reported, purification and detailed characterization of the corresponding enzymes with important functions have rarely been studied. In this study, we isolated and identified 2 critical genes, fcs and ech, encoding feruloyl-CoA synthetase and enoyl-CoA hydratase/aldolase, respectively, which are involved in the vanillin production from ferulic acid. Both genes were heterologously expressed in Escherichia coli, and the resting cell reactions for converting ferulic acid to vanillin were performed. The corresponding crucial enzymes, Fcs and Ech, were purified for the first time and the enzymatic activity of each purified protein was studied. Furthermore, Fcs was comprehensively characterized, at an optimal pH of 7.0 and temperature of 30°C. Kinetic constants for Fcs revealed the apparent Km, kcat, and Vmax values to be 0.35 mM, 67.7 s(-1, and 78.2 U mg(-1, respectively. The catalytic efficiency (kcat/Km value of Fcs was 193.4 mM(-1 s(-1 for ferulic acid. The characterization of Fcs and Ech may be helpful for further research in the field of enzymatic engineering and metabolic regulation.

  9. Structure-function studies of BPP-BrachyNH2 and synthetic analogues thereof with Angiotensin I-Converting Enzyme

    DEFF Research Database (Denmark)

    Arcanjo, Daniel Dias Rufino; Vasconcelos, Andreanne Gomes; Nascimento, Lucas A

    2017-01-01

    The vasoactive proline-rich oligopeptide termed BPP-BrachyNH2 (H-WPPPKVSP-NH2) induces in vitro inhibitory activity of angiotensin I-converting enzyme (ACE) in rat blood serum. In the present study, the removal of N-terminal tryptophan or C-terminal proline from BPP-BrachyNH2 was investigated in ...

  10. Angiotensin-converting enzyme inhibition-induced changes in hippurate renography and renal function in renovascular hypertension

    NARCIS (Netherlands)

    Visscher, C.A; de Zeeuw, D; de Jong, P.E; Piers, D.A; Beekhuis, H; Groothuis, Geny; Huisman, R.M

    1996-01-01

    We studied the mechanism of angiotensin-converting enzyme (ACE) inhibition-induced changes in hippurate renography of the poststenotic kidney. Methods: Ten male mongrel dogs, six with unilateral and four with bilateral renal artery stenosis, were equipped with renal artery blood flow probes and cath

  11. Angiotensin converting enzyme insertion/deletion polymorphism and short-term renal response to ACE inhibition : Role of sodium status

    NARCIS (Netherlands)

    vanderKleij, FGH; Schmidt, A; Navis, GJ; Haas, M; Yilmaz, N; deJong, PE; Mayer, G; deZeeuw, D

    1997-01-01

    Angiotensin converting enzyme (ACEi) inhibition retards renal function loss, but the therapeutic benefit varies between individuals. Renoprotection is poor in patients with the ACE DD genotype. ACE genotype is reported to affect short-term antiproteinuric response to ACEi, a predictor of long-term

  12. The association between angiotensin-converting enzyme gene polymorphism and coronary calcification - The Rotterdam Coronary Calcification Study

    NARCIS (Netherlands)

    Oei, HHS; Sayed-Tabatabaei, FA; Hofman, A; Oudkerk, M; van Duijn, CM; Witteman, JCM

    Background: An insertion/deletion (I/D) polymorphism in the gene encoding angiotensin-converting enzyme (ACE) has been associated with serum ACE levels. The association between the ACE I/D polymorphism and coronary heart disease is unclear. Electron-beam-computed tomography (EBT) is a technique to

  13. The deletion polymorphism of the angiotensin-converting enzyme gene is related to phenotypic differences in human arteries

    NARCIS (Netherlands)

    Buikema, H; Pinto, YM; Rooks, G; Grandjean, JG; Schunkert, H; vanGilst, WH

    We hypothesized that angiotensin-converting enzyme (ACE) insertion/deletion polymorphism may be related to arterial phenotypic differences that could explain the adverse effects of deletion polymorphism. Accordingly, contractile responses to angiotensin I and II (0.1 nmol.l(-1)-1 mu mol.l(-1)),

  14. Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections.

    Science.gov (United States)

    Zou, Zhen; Yan, Yiwu; Shu, Yuelong; Gao, Rongbao; Sun, Yang; Li, Xiao; Ju, Xiangwu; Liang, Zhu; Liu, Qiang; Zhao, Yan; Guo, Feng; Bai, Tian; Han, Zongsheng; Zhu, Jindong; Zhou, Huandi; Huang, Fengming; Li, Chang; Lu, Huijun; Li, Ning; Li, Dangsheng; Jin, Ningyi; Penninger, Josef M; Jiang, Chengyu

    2014-05-06

    The potential for avian influenza H5N1 outbreaks has increased in recent years. Thus, it is paramount to develop novel strategies to alleviate death rates. Here we show that avian influenza A H5N1-infected patients exhibit markedly increased serum levels of angiotensin II. High serum levels of angiotensin II appear to be linked to the severity and lethality of infection, at least in some patients. In experimental mouse models, infection with highly pathogenic avian influenza A H5N1 virus results in downregulation of angiotensin-converting enzyme 2 (ACE2) expression in the lung and increased serum angiotensin II levels. Genetic inactivation of ACE2 causes severe lung injury in H5N1-challenged mice, confirming a role of ACE2 in H5N1-induced lung pathologies. Administration of recombinant human ACE2 ameliorates avian influenza H5N1 virus-induced lung injury in mice. Our data link H5N1 virus-induced acute lung failure to ACE2 and provide a potential treatment strategy to address future flu pandemics.

  15. Identification of a cysteine protease closely related to interleukin-1 beta-converting enzyme.

    Science.gov (United States)

    Faucheu, C; Blanchet, A M; Collard-Dutilleul, V; Lalanne, J L; Diu-Hercend, A

    1996-02-15

    The present study describes the identification and molecular cloning of a new member of the interleukin-1 beta-converting enzyme (ICE) family denoted transcript Y (TY). TY is very closely related to both ICE (51% amino acid identity) and a protein named transcript X (TX) (75% amino acid identity) that we recently identified [Faucheu, C., Diu, A., Chan, A.W.E., Blanchet, A.-M., Miossec, C., Hervé, F.,Collard-Dutilleul, V., Gu, Y., Aldape, R., Lippke, J., Rocher, C., Su, M.S.-S., Livingston, D.J., Hercend, T. & Lalanne, J.-L. (1995) EMBO J. 14, 1914-1922]. The amino acids that are implicated in both the ICE catalytic site and in the PI aspartate-binding pocket are conserved in TY. Within the ICE gene family, TY belongs to a subfamily of proteins closely related to the prototype ICE protein. Using transfection experiments into mammalian cells, we demonstrate that TY has protease activity on its own precursor and that this activity is dependent on the presence of a cysteine residue at position 245. However, despite the close similarity between TY and ICE active sites, TY fails to process the interleukin-1 beta precursor. In addition, as already observed for ICE and TX, TY is able to induce apoptosis when overexpressed in COS cells. TY therefore represents a new member of the growing family of apoptosis-inducing ICE-related cysteine proteases.

  16. PURIFICATION OF ANGIOTENSIN CONVERTING ENZYME INHIBITORY PEPTIDE DERIVED FROM KACANG GOAT MEAT PROTEIN HYDROLYSATE

    Directory of Open Access Journals (Sweden)

    J. Jamhari

    2014-10-01

    Full Text Available The objective of this study was to identify the Angiotensin Converting Enzyme (ACE inhibitorypeptide derived from Kacang goat meat protein hydrolysate. Kacang goat meat loin section washydrolyzed with pepsin, trypsin and chymotrypsin. Protein hydrolysate of Kacang goat meat was thentested the protein concentration and ACE inhibitory activity. ACE inhibitory peptide of the proteinhydrolysate was purified through several steps of purification by column SEP-PAK Plus C18 Cartridgeand RP-HPLC using a Cosmosil column 5PE-SM, 4.6 x 250 mm. The sequence of amino acid of ACEinhibitory peptide was identified by amino acid sequencer. The results showed that amino acidssequence of ACE inhibitory peptide derived from protein hydrolysate of Kacang goat meat was leu-thrglu-ala-pro-leu-asn-pro-lys-ala-arg- asn-glu-lys. It had a molecular weight (MW of 1581 and occurredat the position of 20th to 33rd residues of b-actin of goat meat protein (Capra hircus. The ACE inhibitoryactivity (IC50 of the peptide was 190 mg/mL or 120 mM.

  17. High frequency of the D allele of the angiotensin-converting enzyme gene in Arabic populations

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    Salem Abdel

    2009-06-01

    Full Text Available Abstract Background The angiotensin-converting enzyme (ACE gene in humans has an insertion-deletion (I/D polymorphic state in intron 16 on chromosome 17q23. This polymorphism has been widely investigated in different populations due to its association with the renin-angiotensin system. However, similar studies for Arab populations are limited. This study addresses the distribution of the ACE gene polymorphism in three Arab populations (Egyptians, Jordanians and Syrians. Findings The polymorphisms of ACE gene were investigated using polymerase chain reaction for detection of an I/D mutation. The results showed a high frequency of the ACE D allele among the three Arab populations, Egyptians (0.67, Jordanians (0.66 and Syrians (0.60, which is similar to those obtained from previous studies for Arab populations. Conclusion The relationship between ACE alleles and disease in these three Arab populations is still not known, but the present results clearly suggest that geographic origin should be carefully considered in the increasing number of studies on the association between ACE alleles and disease etiology. This study adds to the data showing the wide variation in the distribution of the ACE alleles in different populations and highlights that great care needs to be taken when interpreting clinical data on the association of the ACE alleles with different diseases.

  18. Expression of tumor necrosis factor-alpha converting enzyme in liver regeneration after partial hepatectomy

    Institute of Scientific and Technical Information of China (English)

    Xian-Ming Lin; Ying-Bin Liu; Fan Zhou; Yu-Lian Wu; Li Chen; He-Qing Fang

    2008-01-01

    AIM:To study the expression of tumor necrosis factor-alpha converting enzyme (TACE) and evaluate its significance in liver regeneration after partial hepatectomy in vivo.METHODS:Male SD rats underwent 70% partial hepatec-tomy.The remaining liver and spleen tissue samples were collected at indicated time points after hepatectomy.TACE expression was investigated by Western blotting,immunohistochemistry,and serial section immunostaining.RESULTS:Expression of TACE in liver and spleen tissues after partial hepatectomy was a time-dependent alteration,reaching a maximal level between 24 and 48 h and remaining elevated for more than 168 h.TACE protein was localized to mononuclear cells (MNC),which infiltrated the liver from the spleen after hepatectomy.The kinetics of TACE expression was in accordance with the number of TACE-staining MNCs and synchronized with those of transforming growth factor-α(TGFα).In addition,TACE-staining MNC partially overlapped with CD3+ T lymphocytes.CONCLUSION:TACE may be involved in liver regenera-tion by pathway mediated with TGFα-EGFR in the cell-cycle progressive phase in vivo.TACE production and effect by paracrine may be a pathway of involvement in liver regeneration for the activated CD3+ T lymphocytes.

  19. Increased risk of pneumonia associated with angiotensin-converting enzyme (CD143) rs4340 polymorphism.

    Science.gov (United States)

    Zhang, Xiaofang; Liu, Fangzhu

    2016-08-01

    The study aims to investigate the genetic association between rs4340 polymorphism at intron 16 of the angiotensin-converting enzyme (CD143) gene and pneumonia predisposition. Electronic database of PubMed, Embase, and CNKI (China National Knowledge Infrastructure) was searched for the studies addressing the association between CD143 rs4340 genotypes and pneumonia risk. The odds ratio (OR) with its 95 % confidence interval (CI) was employed to estimate the association. In total, ten case-control studies, including 1239 pneumonia cases and 2400 healthy controls, met the inclusion criteria. Our results showed a significant association between rs4340 SNP and pneumonia risk using the recessive model (OR 1.43, 95 % CI 1.20-1.70). A significantly increased risk was also indicated under the recessive model in Asian populations (OR 1.63, 95 % CI 1.16-2.30), Caucasian populations (OR 1.34, 95 % CI 1.09-1.65), community-acquired pneumonia (OR 1.42, 95 % CI 1.16-1.75) rather than nosocomial pneumonia (OR 1.47, 95 % CI 0.97-2.23). However, further studies with gene-gene and gene-environmental interactions should be considered to confirm this association.

  20. Early pharmacological inhibition of angiotensin-I converting enzyme activity induces obesity in adulthood

    Directory of Open Access Journals (Sweden)

    Kely ede Picoli Souza

    2015-04-01

    Full Text Available We have investigated early programming of body mass in order to understand the multifactorial etiology of obesity. Considering that the renin-angiotensin system is expressed and functional in the white adipose tissue (WAT and modulates its development, we reasoned whether early transitory inhibition of angiotensin-I converting enzyme activity after birth could modify late body mass development. Therefore, newborn Wistar rats were treated with enalapril (10 mg/kg of body mass or saline, starting at the first day of life until the age of 16 days. Between days 90th and 180th, a group of these animals received high fat diet (HFD. Molecular, biochemical, histological and physiological data were collected. Enalapril treated animals presented hyperphagia, overweight and increased serum level of triglycerides, total cholesterol and leptin, in adult life. Body composition analyses revealed higher fat mass with increased adipocyte size in these animals. Molecular analyses revealed that enalapril treatment increases neuropeptide Y (NPY and cocaine- and amphetamine-regulated transcript (CART gene expression in hypothalamus, fatty acid synthase (FAS and hormone-sensitive lipase (HSL gene expression in retroperitoneal WAT and decreases peroxixome proliferators-activated receptor (PPAR γ, PPARα, uncoupling protein (UCP 2 and UCP3 gene expression in WAT. The results of the current study indicate that enalapril administration during early postnatal development increases body mass, adiposity and serum lipids in adulthood associated with enhanced food intake and decreased metabolic activity in WAT, predisposing to obesity in adulthood.