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1.
J Agric Food Chem ; 68(3): 759-768, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31841328

RESUMO

In this study, we investigated the antihypertensive effects in vitro and in vivo of novel angiotensin-converting enzyme inhibitory (ACEI) peptides purified and identified from bovine bone gelatin hydrolysate (BGH). Thirteen ACEI peptides were identified from BGH, and among which, RGL-(Hyp)-GL and RGM-(Hyp)-GF exhibited high ACE inhibition with IC50 values of 1.44 and 10.23 µM. Molecular docking predicted that RGM-(Hyp)-GF and ACE residues of Glu384, His513, and Lys511 formed hydrogen-bonding interactions at distances of 2.57, 2.99, and 2.42 + 3.0 Å. RGL-(Hyp)-GL formed hydrogen bonds with Lys511 and Tyr523 and generated hydrogen-bonding interactions with His387 and Glu411 in the zinc(II) complexation motif at distances of 2.74 and 3.03 + 1.93 Å. The maximal decrements in systolic blood pressure in spontaneously hypertensive rats induced by one-time gavage of RGL-(Hyp)-GL and RGM-(Hyp)-GF at 30 mg/kg were 31.3 and 38.6 mmHg. RGL-(Hyp)-GL had higher enzyme degradation resistance than that of RGM-(Hyp)-GF in vitro incubation in rat plasma, and they were sequentially degraded into pentapeptides and tetrapeptides within 2 h. Our results indicate that BGH can serve as a nutritional candidate to control blood pressure.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/química , Anti-Hipertensivos/química , Osso e Ossos/química , Gelatina/química , Peptídeos/química , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/isolamento & purificação , Animais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/isolamento & purificação , Pressão Sanguínea/efeitos dos fármacos , Bovinos , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Simulação de Acoplamento Molecular , Peptídeos/administração & dosagem , Peptídeos/isolamento & purificação , Peptidil Dipeptidase A/química , Hidrolisados de Proteína/química , Ratos , Ratos Endogâmicos SHR
2.
J Sci Food Agric ; 100(1): 315-324, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31525262

RESUMO

BACKGROUND: In order to utilize tilapia skin gelatin hydrolysate protein, which is normally discarded as industrial waste in the process of fish manufacture, we study the in vivo and in vitro angiotensin-I-converting enzyme (ACE) inhibitory activity of the peptide Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP). The aim was to provide a pharmacological basis of the development of minimal side effects of ACE inhibitors by comparative analysis with captopril in molecular docking. RESULTS: This peptide from protein-rich wastes showed excellent ACE inhibitory activity (IC50  = 2.577 µmol L-1 ) and exhibited a mixed noncompetitive inhibitory pattern with Lineweaver-Burk plots. Furthermore, LSGYGP and captopril groups both showed significant decreases in blood pressure after 6 h and maintained good digestive stability over 4 h. Molecular bond interactions differentiate competitive captopril upon hydrogen bond interactions and Zn(II) interaction. The C-terminal Pro generates three interactions (hydrogen bonds, hydrophilic interactions and Van der Waals interactions) in the peptide and effectively interacts with the S1 and S2 pockets of ACE. CONCLUSION: LSGYGP, with an IC50 value of 2.577 µmol L-1 , has an antihypertensive effect in spontaneously hypertensive rats. Through comparison with captopril, this study revealed that LSGYGP may be a potential food-derived ACE inhibitory peptide and could act as a functional food ingredient to prevent hypertension. © 2019 Society of Chemical Industry.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/química , Anti-Hipertensivos/química , Captopril/química , Hipertensão/tratamento farmacológico , Peptídeos/química , Sequência de Aminoácidos , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Animais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Captopril/administração & dosagem , Ciclídeos , Digestão , Proteínas de Peixes/química , Trato Gastrointestinal/metabolismo , Humanos , Ligações de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Cinética , Masculino , Simulação de Acoplamento Molecular , Peptídeos/metabolismo , Peptídeos/farmacologia , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Hidrolisados de Proteína/química , Hidrolisados de Proteína/metabolismo , Ratos , Ratos Endogâmicos SHR
3.
Rev Cardiovasc Med ; 20(3): 111-120, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31601085

RESUMO

Randomized controlled trials have demonstrated the benefits of guideline-directed medical therapy in the outpatient setting for treatment of chronic heart failure. However, the benefits of continuation (or discontinuation) of major chronic heart failure therapies when treating acute heart failure during hospitalization are less clear. Real and anticipated worsening renal function, hyperkalemia and hypotension are the three major reasons for discontinuation of renin-angiotensin-aldosterone system inhibitors during hospitalization, and a failure to resume renin-angiotensin-aldosterone system inhibitors before discharge could worsen cardiovascular outcomes. Available data, mostly observational, shows that continuation or initiation of renin-angiotensin-aldosterone system inhibitors appears efficacious, safe, and well tolerated in majority of acute heart failure patients during hospitalization. Worsening renal function portends poor prognosis only if associated with congestion in acute heart failure, and clinicians should not de-escalate diuretic therapy routinely for worsening renal function.


Assuntos
Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Síndrome Cardiorrenal/tratamento farmacológico , Diuréticos/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Admissão do Paciente , Sistema Renina-Angiotensina/efeitos dos fármacos , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Síndrome Cardiorrenal/diagnóstico , Síndrome Cardiorrenal/mortalidade , Síndrome Cardiorrenal/fisiopatologia , Tomada de Decisão Clínica , Diuréticos/efeitos adversos , Esquema de Medicação , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Fatores de Risco , Resultado do Tratamento
4.
J Agric Food Chem ; 67(37): 10313-10320, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31502448

RESUMO

A peptide fraction with molecular masses below 3 kDa (PSH-3 kDa) from a peach seed hydrolysate demonstrated high angiotensin converting enzyme (ACE) inhibitory activity (concentration to inhibit 50% ACE (IC50) = 16.4 µg/mL) in our previous work. This work proposes a further study of this highly active fraction. RP-HPLC enabled two fractions (F3 and F4) with high inhibitory activity (IC50 = 2.0 ± 0.5 and 1.2 ± 0.2 µg/mL, respectively) to be isolated. Peptide analysis by LC-Q-TOF-MS/MS using reverse-phase and hydrophilic interaction chromatography enabled 33 peptides within both fractions to be identified. Among them, peptide isoleucine-tyrosine-serine-proline-histidine (IYSPH) showed the highest capacity. The lack of cytotoxicity of peptides was demonstrated in three different cell lines (HeLa, HT-29, and HK-2). Oral administration of PSH-3 kDa fraction or peptide IYSPH caused a significant systolic blood pressure reduction (-30 mmHg) on spontaneously hypertensive rats after 3-6 h treatment.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/química , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/química , Hipertensão/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Prunus persica/química , Inibidores da Enzima Conversora de Angiotensina/isolamento & purificação , Animais , Anti-Hipertensivos/isolamento & purificação , Pressão Sanguínea/efeitos dos fármacos , Humanos , Hipertensão/enzimologia , Hipertensão/fisiopatologia , Masculino , Peptidil Dipeptidase A/metabolismo , Extratos Vegetais/isolamento & purificação , Hidrolisados de Proteína/química , Ratos , Ratos Endogâmicos SHR , Sementes/química
5.
J Sci Food Agric ; 99(15): 6822-6832, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31385307

RESUMO

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitory peptides were found to alleviate acute hepatitis significantly. In this study, we purified and identified ACE inhibitory peptide from cashew to evaluate its protective role on alcohol-induced acute hepatitis in mice. RESULTS: The ACE inhibitory peptides were purified by using consecutive chromatographic techniques. One of these peptides (FETISFK) exhibited the highest ACE inhibition rate (91.04 ± 0.31%). In vivo, the results showed that ACE inhibitory peptide decreased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) caused by alcohol exposure. Moreover, it could increase the activities of superoxide dismutase (SOD) and glutathione (GSH), and decrease the level of malondialdehyde (MDA). It was also found to down-regulate markedly the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). It could also decrease the expression of ACE, angiotensin II (AngII) and angiotensin II type 1 receptor (AT1 R). CONCLUSION: These findings support the view that the ACE inhibitory peptide alleviated acute hepatitis by down-regulating the ACE-AngII-AT1 R axis, broadening the research approach to prevent acute hepatitis, and providing experimental data for the development and utilization of cashews. © 2019 Society of Chemical Industry.


Assuntos
Anacardium/química , Inibidores da Enzima Conversora de Angiotensina/química , Hepatite/tratamento farmacológico , Peptídeos/química , Extratos Vegetais/química , Doença Aguda/terapia , Álcoois/efeitos adversos , Angiotensina II/genética , Angiotensina II/metabolismo , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/isolamento & purificação , Animais , Aspartato Aminotransferases/genética , Aspartato Aminotransferases/metabolismo , Hepatite/enzimologia , Hepatite/etiologia , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , Nozes/química , Peptídeos/administração & dosagem , Peptídeos/isolamento & purificação , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
6.
Lancet ; 394(10205): 1254-1263, 2019 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-31447116

RESUMO

BACKGROUND: Guideline-recommended doses of angiotensin-converting-enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs), and ß blockers are similar for men and women with heart failure with reduced ejection fraction (HFrEF), even though there are known sex differences in pharmacokinetics of these drugs. We hypothesised that there might be sex differences in the optimal dose of ACE inhibitors or ARBs and ß blockers in patients with HFrEF. METHODS: We did a post-hoc analysis of BIOSTAT-CHF, a prospective study in 11 European countries of patients with heart failure in whom initiation and up-titration of ACE inhibitors or ARBs and ß blockers was encouraged by protocol. We included only patients with left ventricular ejection fraction less than 40%, and excluded those who died within the first 3 months. Primary outcome was a composite of time to all-cause mortality or hospitalisation for heart failure. Findings were validated in ASIAN-HF, an independent cohort of 3539 men and 961 women with HFrEF. FINDINGS: Among 1308 men and 402 women with HFrEF from BIOSTAT-CHF, women were older (74 [12] years vs 70 [12] years, p<0·0001) and had lower bodyweights (72 [16] kg vs 85 [18] kg, p<0·0001) and heights (162 [7] cm vs 174 [8] cm, p<0·0001) than did men, although body-mass index did not differ significantly. A similar number of men and women reached guideline-recommended target doses of ACE inhibitors or ARBs (99 [25%] vs 304 [23%], p=0·61) and ß blockers (57 [14%] vs 168 [13%], p=0·54). In men, the lowest hazards of death or hospitalisation for heart failure occurred at 100% of the recommended dose of ACE inhibitors or ARBs and ß blockers, but women showed approximately 30% lower risk at only 50% of the recommended doses, with no further decrease in risk at higher dose levels. These sex differences were still present after adjusting for clinical covariates, including age and body surface area. In the ASIAN-HF registry, similar patterns were observed for both ACE inhibitors or ARBs and ß blockers, with women having approximately 30% lower risk at 50% of the recommended doses, with no further benefit at higher dose levels. INTERPRETATION: This study suggests that women with HFrEF might need lower doses of ACE inhibitors or ARBs and ß blockers than men, and brings into question what the true optimal medical therapy is for women versus men. FUNDING: European Commission.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Estudos Prospectivos , Fatores Sexuais , Volume Sistólico/efeitos dos fármacos
7.
Hypertension ; 74(4): 896-902, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31378100

RESUMO

Early and preferential activation of cardiac sympathetic nerve activity (CSNA) is one of the strongest prognostic markers of heart failure (HF) in patients. Our previous studies have implicated central angiotensin mechanisms as playing a critical role in generating this increase in cardiac sympathetic drive. However, it is unclear if inhibition of AT1R (angiotensin type-1 receptors) in different neural groups in the sympathetic pathway to the heart, such as the sympathetic preganglionic neurons in the intermediolateral column of the spinal cord, can reduce cardiac sympathetic drive. We hypothesized that in HF, localized intrathecal administration of the AT1R antagonist losartan, specifically into the T1-2 subarachnoid space, would decrease CSNA. In normal conscious sheep, intrathecal infusion of Ang II (angiotensin II; 3.0 nmol/mL per hour), significantly increased mean arterial pressure and CSNA; this effect was abolished by prior administration of losartan (1 mg/h). In an ovine rapid ventricular pacing model of HF, the resting levels of heart rate and CSNA were significantly elevated compared with normals. Intrathecal infusion of losartan (1 mg/h) in HF significantly reduced CSNA and heart rate but did not change arterial pressure. The AT1R binding density in the spinal cord was also elevated in the HF group. Our data suggest that AT1Rs within the spinal cord are responsible, in part, for the increased CSNA in HF and may represent a target for the selective reduction of CSNA in HF.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Gânglios Simpáticos/efeitos dos fármacos , Insuficiência Cardíaca/fisiopatologia , Losartan/administração & dosagem , Sistema Nervoso Simpático/efeitos dos fármacos , Animais , Pressão Arterial/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Feminino , Gânglios Simpáticos/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Injeções Espinhais , Ovinos , Sistema Nervoso Simpático/fisiopatologia
8.
Clín. investig. arterioscler. (Ed. impr.) ; 31(4): 166-177, jul.-ago. 2019. ilus
Artigo em Espanhol | IBECS | ID: ibc-182711

RESUMO

El aneurisma de aorta abdominal (AAA) es una patología vascular con una elevada tasa de morbimortalidad y una prevalencia que, en varones de más de 65 años, puede alcanzar el 8%. En esta enfermedad, habitualmente asintomática, se produce una dilatación progresiva de la pared vascular que puede llevar a su rotura, un fenómeno mortal en más de un 80% de los casos. El tratamiento de los pacientes con aneurismas asintomáticos se limita al seguimiento periódico con pruebas de imagen, el control de los factores de riesgo cardiovascular y un tratamiento con terapia antiagregante y estatinas, si bien actualmente no existe ningún tratamiento farmacológico efectivo capaz de limitar su progresión o evitar su rotura. En la actualidad el diámetro aórtico es el único marcador de riesgo de rotura y determina la necesidad de reparación quirúrgica cuando alcanza valores superiores a 5,5 cm. En esta revisión se tratan los principales aspectos relacionados con la epidemiología, los factores de riesgo, el diagnóstico y el manejo terapéutico del AAA, se exponen las dificultades para disponer de buenos biomarcadores de esta enfermedad y se describen las estrategias para la identificación de nuevas dianas terapéuticas y biomarcadores en el AAA


Abdominal aortic aneurysm (AAA) is a vascular pathology with a high rate of morbidity and mortality and a prevalence that, in men over 65 years, can reach around 8%. In this disease, usually asymptomatic, there is a progressive dilatation of the vascular wall that can lead to its rupture, a fatal phenomenon in more than 80% of cases. The treatment of patients with asymptomatic aneurysms is limited to periodic monitoring with imaging tests, control of cardiovascular risk factors and treatment with statins and antiplatelet therapy. There is no effective pharmacological treatment capable of limiting AAA progression or avoiding their rupture. At present, the aortic diameter is the only marker of risk of rupture and determines the need for surgical repair when it reaches values greater than 5.5 cm. This review addresses the main aspects related to epidemiology, risk factors, diagnosis and clinical management of AAA, exposes the difficulties to have good biomarkers of this pathology and describes the strategies for the identification of new therapeutic targets and biomarkers in AAA


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Aneurisma da Aorta Abdominal/epidemiologia , Aneurisma da Aorta Abdominal/fisiopatologia , Biomarcadores/análise , Sistemas de Liberação de Medicamentos/métodos , Aneurisma da Aorta Abdominal/terapia , Hipertensão/complicações , Uso de Tabaco/epidemiologia , Doença Arterial Periférica/fisiopatologia , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem
9.
Biomed Res Int ; 2019: 9463872, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31179336

RESUMO

Background: Optimal use of angiotensin-converting enzyme inhibitors (ACEIs) is crucial to improve the treatment outcome in heart failure patients. However, little is known about the optimal use of ACEIs among heart failure patients in our setting. Therefore, our study aimed to investigate the utilization and optimal dosing of ACEIs and associated factors in heart failure patients. Method: A cross-sectional study was conducted on randomly selected patients with heart failure between February 2016 and June 2016 at ambulatory care clinic of Jimma University Medical Center, Ethiopia. Data were collected through patient interview and review of medical records. Binary logistic regression analysis was done to identify factors associated with utilization and optimal dosing of ACEIs. Results: A total of 308 patients were included in the final analysis of this study. The mean (±standard deviation) age of the patients was 52.3 ±15.5 years. Out of the total, 74.7% of the patients were receiving ACEIs. Among the patients who were receiving ACEIs, only 35.7% were taking optimal dose. New York Heart Association (NYHA) class III (Adjusted odds ratio (AOR):0.12, 95% confidence interval (CI):0.02-0.98), valvular heart disease (AOR: 0.27, 95% CI: 0.13-0.56), hypertension (AOR: 5.82, 95% CI: 2.16-15.71), and diabetes mellitus (AOR: 3.84, 95% CI: 1.07-13.86) were significantly associated with the use of ACEIs, whereas age ≥65 (AOR: 2.61, 95%CI: 1.20-5.64), previous hospitalization for heart failure (AOR: 2.08, 95%CI: 1.11-3.92), diuretic use (AOR: 5.60, 95%CI: 2.75-11.40), and dose of furosemide >40mg (AOR: 9.80, 95%CI: 3.00-31.98) were predictors of suboptimal dosing of ACEIs. Conclusion: Although majority of patients were receiving ACEIs, only about one-third were using optimal dosage. Valvular heart disease and NYHA class III were negatively associated with the use of ACEIs while previous hospitalization for heart failure, old age, diuretic use, and diuretic dose were predictors of suboptimal dosing of ACEIs. Therefore, more effort needs to be done to minimize the potentially modifiable risk factors of suboptimal use of ACEIs therapy in heart failure patients.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Uso de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Adulto , Idoso , Estudos Transversais , Diabetes Mellitus/tratamento farmacológico , Etiópia , Feminino , Doenças das Valvas Cardíacas/tratamento farmacológico , Hospitalização , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Razão de Chances , Ambulatório Hospitalar , Fatores de Risco , Resultado do Tratamento
10.
J Agric Food Chem ; 67(24): 6757-6764, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31184153

RESUMO

In the present study we purified and identified peptides from broccoli protein hydrolysates and evaluated their angiotensin-converting enzyme (ACE) inhibitory activity in vitro and hypotensive effect in vivo. Three ACE inhibitory peptides were isolated and identified as IPPAYTK, LVLPGELAK, and TFQGPPHGIQVER, and their inhibitory IC50 values were 23.5, 184.0, and 3.4 µM, respectively. We then investigated the effect of gastrointestinal digestion on ACE inhibitory activity. We detected almost two times the ACE inhibitory activity of the peptide LVLPGELAK following simulated digestion than prior to digestion. LVLPGE and LAK, two novel peptides exhibiting high ACE inhibitory activity, were discovered following digestion and possessed IC50 values of 13.5 and 48.0 µM, respectively. The hypotensive effect of the peptides was assessed after oral administration to spontaneous hypertensive rats (SHRs). We found that LVLPGE and LAK demonstrated a significant hypotensive effect in vivo. Protein from broccoli may thus constitute a potential antihypertensive peptide source.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Brassica/química , Hipertensão/tratamento farmacológico , Peptídeos/administração & dosagem , Proteínas de Plantas/química , Administração Oral , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/isolamento & purificação , Animais , Anti-Hipertensivos/química , Anti-Hipertensivos/isolamento & purificação , Pressão Sanguínea/efeitos dos fármacos , Feminino , Humanos , Hipertensão/enzimologia , Hipertensão/fisiopatologia , Mapeamento de Peptídeos , Peptídeos/isolamento & purificação , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Hidrolisados de Proteína/química , Ratos , Ratos Endogâmicos SHR
11.
Hypertension ; 74(2): 285-294, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31230551

RESUMO

The renin-angiotensin system plays an important role in the development and progression of heart failure (HF). In addition to the classical renin-angiotensin pathway, an alternative pathway produces Angs (angiotensins), which counteract the negative effects of Ang II. We hypothesized that Ang profiling could provide insights into the pathogenesis and prognosis of HF with preserved ejection fraction. We aimed to investigate the effects of Angs on outcome in HF with preserved ejection fraction. Consecutive patients were included into a prospective single-center registry. Clinical, laboratory, and imaging parameters were assessed and serum samples were taken at baseline and measured by mass spectroscopy. Serum equilibrium levels were analyzed in regard to the combined clinical end point of cardiovascular death or HF hospitalization. In total, 155 patients were included during a median follow-up time of 22.5 (interquartile range, 4.0-61.0) months, 52 individuals (34%) reached the combined end point. We identified higher levels of Ang 1-7 and Ang 1-5 as predictors for poor outcome. After adjusting for potential confounding factors, Ang 1-5 remained predictive for poor outcome. In addition to Ang 1-7 and Ang 1-5, the novel ACE (angiotensin-converting enzyme) independent Ang composite marker [Ang 1-7+Ang 1-5] was shown to predict adverse events. We conclude that Angs of the alternative renin-angiotensin system seem to play a role in HF with preserved ejection fraction and are linked to outcome in patients with HF and preserved ejection fraction. Ang 1-5 and the alternative renin-angiotensin system composite marker [Ang 1-7+Ang 1-5] are independent predictors of outcome.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Angiotensinas/metabolismo , Causas de Morte , Insuficiência Cardíaca/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Volume Sistólico/fisiologia , Centros Médicos Acadêmicos , Idoso , Áustria , Estudos de Coortes , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Análise Multivariada , Peptidil Dipeptidase A/metabolismo , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Sistema de Registros , Medição de Risco , Volume Sistólico/efeitos dos fármacos , Análise de Sobrevida
13.
Oral Dis ; 25(6): 1634-1644, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31066953

RESUMO

OBJECTIVE: The purpose of this case-control study was to compare the pharmacological anamnesis collected from a group of 150 burning mouth syndrome (BMS) patients with that of a control group of 150 patients matched for age and sex. MATERIALS AND METHODS: The patients' medical histories were reviewed, and data on drug therapy were collected. Drugs were classified on the basis of pharmacological effects; the classes were antihypertensives (i.e., ACE inhibitors/ARBs, calcium antagonists, diuretics and beta-blockers), antiaggregants, anticoagulants, antidiabetics, vitamin D integrators, bisphosphonates, psychotropics (i.e., anxiolytics and antidepressants), gastroprotectors, statins, thyroid hormone substitutes, corticosteroids and immunosuppressants. RESULTS: The BMS patients and the controls were matched for age (mean age: 69 years) and sex (128 females and 22 males). Antihypertensives, especially ACE inhibitors/ARBs (OR = 0.37, CI: 0.22-0.63, p = 0.0002) and beta-blockers (OR = 0.36, CI: 0.19-0.68 p = 002), revealed an inverse association with the presence of BMS, whereas anxiolytics (OR = 3.78, CI: 2.12-6.75 p < 0.0001), but neither antidepressants nor antipsychotics, were significantly associated with BMS. There were no correlations with other drug classes. CONCLUSION: Our study highlighted that ACE inhibitors, ARBs and beta-blockers were in inverse relation to BMS and found that anxiolytics, but neither antidepressants nor antipsychotics, were linked to the presence of the syndrome.


Assuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Antidepressivos/efeitos adversos , Antipsicóticos/efeitos adversos , Síndrome da Ardência Bucal , Antagonistas Adrenérgicos beta/administração & dosagem , Adulto , Idoso , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Antidepressivos/administração & dosagem , Antipsicóticos/administração & dosagem , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
J Agric Food Chem ; 67(25): 7147-7156, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31140270

RESUMO

Egg proteins are recognized as excellent sources of bioactive peptides, such as angiotensin-converting enzyme inhibitory (ACEi) peptides. Oral administration of a thermolysin-digested egg white hydrolysate (T-EWH) caused a significant blood pressure reduction in spontaneously hypertensive rats; a further ACEi assay implied that its ACEi activity was enhanced after in vitro gastrointestinal (GI) digestion. These results indicated that T-EWH contained ACEi peptides resisting GI digestion and/or being further released during GI digestion. Therefore, the objective of this study was to identify these responsible ACEi peptides from T-EWH. The conventionally activity-guided fractionation was applied, coupled with a synchronized GI digestion throughout, during which both peptide yield and ACEi activity before and after the GI digestion were measured. Finally, six ACEi peptides (LAPYK, LKISQ, LKYAT, INKVVR, LFLIKH, and LGHWVY) with good GI resistance were identified with IC50 values <20 µM, especially LKYAT (0.09 µM). The structure-activity relationship of these peptides was discussed. The discovery of GI-resistant ACEi peptides could further support the application of egg white proteins as functional food ingredients.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/química , Proteínas do Ovo/química , Trato Gastrointestinal/metabolismo , Hipertensão/metabolismo , Peptídeos/química , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Galinhas , Digestão , Clara de Ovo/química , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Peptídeos/administração & dosagem , Peptídeos/metabolismo , Peptidil Dipeptidase A/química , Hidrolisados de Proteína/química , Ratos , Ratos Endogâmicos SHR
15.
Rev Med Chil ; 147(2): 173-180, 2019 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-31095165

RESUMO

BACKGROUND: To reduce the progression of chronic kidney disease (CKD) and cardiovascular risk, the guidelines recommend the blockade of the renin-angiotensin-aldosterone system (RAAS) in patients with proteinuria. AIM: To assess the frequency of enalapril or losartan use in diabetics or hypertensive patients with stage 3 CKD. MATERIAL AND METHODS: Review of clinical records of patients with CKD in an urban primary care clinic. RESULTS: We identified 408 subjects aged 40 to 98 years (66% women) with stage 3 CKD. Sixty six percent had only hypertension and 34% were diabetic with or without hypertension. Seventy four percent received RAAS blockers (52% used enalapril, 45% losartan and 2% both medications). RAAS blockers were used in 70% of hypertensive and 78% of diabetic patients. The prescription in hypertensive diabetics with microalbuminuria was lower than in those without microalbuminuria (72% vs 87%, p < 0.05), but the opposite occurred in pure hypertensive patients with and without microalbuminuria (88% vs 69%, p < 0.05). There were no significant differences in blood pressure levels, microalbuminuria or serum potassium levels between RAAS blocker users and non-users. No differences were observed either between enalapril and losartan users. CONCLUSIONS: The adherence to clinical guidelines is insufficient and users of the recommended drugs did not achieve the expected goals.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Enalapril/uso terapêutico , Losartan/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminúria/urina , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/normas , Creatinina/sangue , Diabetes Mellitus/tratamento farmacológico , Progressão da Doença , Quimioterapia Combinada , Enalapril/administração & dosagem , Enalapril/normas , Feminino , Humanos , Hipertensão/tratamento farmacológico , Losartan/administração & dosagem , Losartan/normas , Masculino , Pessoa de Meia-Idade , Proteinúria/urina , Sistema Renina-Angiotensina , Cooperação e Adesão ao Tratamento/psicologia
16.
Hypertension ; 74(1): 35-46, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31132956

RESUMO

Previous evidence suggests modest improvements in antihypertensive medication adherence occurred from 2007 to 2012 among US adults ≥65 years of age. Whether adherence improved over time among adults <65 years of age is unknown. We assessed trends in antihypertensive medication nonpersistence and low adherence among 379 658 commercially insured adults <65 years of age initiating treatment in 2007-2014 using MarketScan claims. Nonpersistence was defined as having no days of medication available to take during the final 90 days of the 365 days following initiation. Among beneficiaries who were persistent to treatment, low adherence was defined by having antihypertensive medication available to take for <80% of the days in the 365 days following initiation (ie, proportion of days covered <80%). In 2007 and 2014, 23.3% and 23.5% of patients were nonpersistent to treatment, respectively, and 42.3% and 40.2% had low adherence, respectively. The relative risks for nonpersistence and low adherence were lower among beneficiaries initiating treatment with an angiotensin-converting enzyme inhibitor (0.95; 95% CI, 0.94-0.97 and 0.97; 95% CI, 0.96-0.98, respectively), angiotensin receptor blocker (0.86; 95% CI, 0.85-0.88 and 0.99; 95% CI, 0.97-1.00, respectively), or multiclass regimen (0.82; 95% CI, 0.80-0.84 and 0.88; 95% CI, 0.86-0.89, respectively), prescribed 90-day versus 30-day prescriptions (0.67; 95% CI, 0.66-0.68 and 0.70; 95% CI, 0.69-0.71, respectively), or who received medications by mail versus at the pharmacy (0.93; 95% CI, 0.90-0.95 and 0.90; 95% CI, 0.88-0.92, respectively). In conclusion, several modifiable factors were associated with lower rates of both antihypertensive medication nonpersistence and low adherence among adults <65 years of age initiating treatment in 2007-2014.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , Anti-Hipertensivos/farmacologia , Estudos de Coortes , Intervalos de Confiança , Bases de Dados Factuais , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Determinação de Necessidades de Cuidados de Saúde , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Estados Unidos
17.
Int J Clin Pharmacol Ther ; 57(8): 393-401, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31131826

RESUMO

OBJECTIVE: Managing hypertension to prevent complications in patients with diabetes requires appropriate pharmacotherapy. This study aimed to analyze healthcare provider factors influencing prescriptions of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) as the first-line therapy in managing hypertension among patients with diabetes in primary care. MATERIALS: This study used National Health Insurance Claims Data in Korea. METHODS: We calculated the prescription rate of angiotensin-converting enzyme inhibitors (ACE inhibitors) or ARBs by dividing the number of patients prescribed an ACE inhibitor or an ARB by the number of patients with diabetes prescribed hypoglycemic agents and antihypertensive agents. We performed a logistic regression to investigate the factors influencing the prescription rate of ACE inhibitors or ARBs. RESULTS: The mean prescription rate of ACE inhibitors or ARBs was 69.8%. The prescription rate of ACE inhibitors or ARBs decreased with increasing physician and patient age. The rate was higher for male patients than for females. The rate was higher in institutions with a greater number of physicians and among internists than among general practitioners, surgery-related and internal medicine-related specialists. The rate was significantly influenced by the mean monthly number of patients with hypertension per medical institution, the number of physicians per medical institution, and the physician's age and specialty. CONCLUSION: The age and specialty of the prescribing physician influenced the use of ACE inhibitors or ARBs in patients with diabetes and hypertension in primary care. Efforts are needed to promote information exchange among physicians and the appropriate prescriptions of antihypertensive agents in patients with diabetes and hypertension in primary care.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Diabetes Mellitus , Hipertensão/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Fatores Etários , Feminino , Humanos , Hipertensão/complicações , Hipoglicemiantes/administração & dosagem , Masculino , República da Coreia , Especialização
18.
Ter Arkh ; 91(1): 101-107, 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-31090380

RESUMO

In conditions of climate warming with an increase in heat waves associated with an increase in cardiovascular morbidity and mortality, the particular interest is the effect of cardiovascular drugs on adaptation to high temperatures. The review reflects the results of European and domestic studies on the safety of therapy during long and short heat waves. Recommendations for the correction of therapy during this period are given. Self-control of blood pressure (SCAD) is a mandatory component of the therapy of arterial hypertension during heat waves. With the development of clinically significant hypotension, a reduction in the dose of antihypertensive drugs is necessary. It is recommended to start with a dose reduction and/or withdrawal of diuretics and nitrates. Not recommended the complete abolition of antihypertensive therapy because of the risk of hypertensive crises, characteristic of abnormal heat, as well as due to the increase in blood pressure when the weather changes and the temperature drops. With increasing blood pressure during heat waves, it is recommended to give preference to calcium channel antagonists, angiotensin converting enzyme inhibitors (ACE inhibitors) and selective beta-blockers. It is necessary to inform patients about the additional protective effect of statins in order to increase adherence to therapy. Patients taking diuretics require individual daily monitoring of fluid intake and body weight. An overview of recommendations on sanogenic behavior during heat waves is given. Details are considered rules for the use of air conditioning, methods of diagnosis of dehydration and drinking mode Keywords: heat waves, cardiovascular complications, preventive measures.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Bloqueadores dos Canais de Cálcio/administração & dosagem , Doenças Cardiovasculares/tratamento farmacológico , Calor Extremo/efeitos adversos , Hipertensão/tratamento farmacológico , Raios Infravermelhos/efeitos adversos , Antagonistas Adrenérgicos beta/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Hipertensivos/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/mortalidade , Diuréticos/efeitos adversos , Diuréticos/farmacologia , Humanos , Estações do Ano
19.
Drugs Aging ; 36(7): 667-674, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30949984

RESUMO

BACKGROUND: The use of renin-angiotensin-aldosterone system inhibitors has increased over the past few years. There are conflicting data as to their relationship with acute kidney injury following surgery. OBJECTIVES: The objective of the article was to evaluate the risk of acute kidney injury in diabetic older patients treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and their medical outcomes following fragility hip fracture surgery. METHODS: Consecutive diabetic patients presenting with fragility hip fractures to our primary trauma center between January 2012 and June 2016 were included. Demographic and clinical data, including co-morbidities, medication use, and laboratory results, were collected from the electronic medical records. The primary outcome was the incidence of acute kidney injury; the secondary outcome was 1-year mortality. RESULTS: Two hundred and seventeen patients were included; 125 were receiving treatment with medications targeting the renin-angiotensin-aldosterone system. Demographic and clinical characteristics were similar between groups. No association was found between the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and the risk of acute kidney injury, which occurred in 25% of the cohort. Univariate analysis revealed that diuretic use, particularly furosemide, increased the risk of acute kidney injury during hospitalization (p = 0.003). However, in a multivariate analysis, only age and estimated glomerular filtration rates were associated with an increased risk of acute kidney injury. Patients with acute kidney injury were found to have increased mortality during the first post-operative year (p < 0.001). CONCLUSIONS: Acute kidney injury is a frequent complication after hip fracture surgery in elderly diabetic patients and is associated with increased 1-year mortality; however, it was not found to be associated with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker pre-fracture treatment.


Assuntos
Lesão Renal Aguda/etiologia , Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Diabetes Mellitus/tratamento farmacológico , Fraturas do Quadril/cirurgia , Lesão Renal Aguda/induzido quimicamente , Fatores Etários , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Angiotensinogênio , Estudos de Coortes , Diabetes Mellitus/fisiopatologia , Feminino , Taxa de Filtração Glomerular , Humanos , Incidência , Masculino , Sistema Renina-Angiotensina/efeitos dos fármacos , Estudos Retrospectivos
20.
Trials ; 20(1): 160, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30836981

RESUMO

BACKGROUND: Chronic treatment of hypertension or heart failure very often includes an angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) as renin-angiotensin system inhibitors (RASi) treatments. To stop or not to stop these medications before major surgery remains an unresolved issue. The lack of evidence leads to conflicting guidelines with respect to RASi management before major surgery. The purpose of this study is to evaluate the impact of a strategy of RASi continuation or discontinuation on perioperative complications in patients undergoing major non-cardiac surgery. METHODS: This is a multicenter, open-labeled randomized controlled trial in > 30 French centers. In the experimental group, RASi will be continued while the treatment will be stopped 48 h before the surgery in the control arm. The primary endpoint is a composite endpoint of major complications after surgery. An endpoint adjudication committee will review clinical data and adjudicate efficacy endpoints while blinded to the assigned study drug group. Main analysis will be by intention-to-treat comparing the composite outcome measure at 28 days in the two groups. A total of 2222 patients are planned to detect an absolute complications difference of 5%. DISCUSSION: The results of the trial should provide robust evidence to anesthesiologists and surgeons regarding management of RASi before major non-cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03374449 . Registered on 11 December 2017.


Assuntos
Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Hipertensão/tratamento farmacológico , Assistência Perioperatória/métodos , Sistema Renina-Angiotensina/efeitos dos fármacos , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Esquema de Medicação , França , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Estudos Multicêntricos como Assunto , Assistência Perioperatória/efeitos adversos , Complicações Pós-Operatórias/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
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