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1.
Anticancer Res ; 39(9): 4597-4602, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519556

RESUMO

Our previous review of the literature assessed the existing knowledge (until 2000) about the possible link between angiotensin-converting enzyme inhibitors (ACEIs) and factors influencing the development of malignancies. We reviewed the literature for reports of statistical associations (or lack thereof) between ACEi treatment and incidence of specific cancers (e.g. breast, gastrointestinal, and skin). We concluded then that results from the epidemiological studies are conflicting, even taking the different methodology and endpoints into consideration, and thus inconclusive. Further investigation is needed beyond the observation period of most of these studies, and additional experimental studies are needed also to study the mechanisms by which agents blocking the renin-angiotensin system may obtain their inhibitory effect on tumor growth and metastasis. The present review elaborates further with more recent evidence from numerous human clinical studies from the past two decades (including large epidemiological studies, and long-term prospective and retrospective studies) on a protective association between ACEi treatment and the prognosis of patients with specific cancer types, malignancy characteristics or stage. Moreover, treatment with ACEI/angiotensin receptor blockers represents an adjuvant therapy with synergistic effects to chemotherapy and may improve patient outcomes (i.e. progression-free survival, and prolonged overall survival) in different types of cancers.


Assuntos
Neoplasias/metabolismo , Neoplasias/mortalidade , Sistema Renina-Angiotensina/efeitos dos fármacos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Clínicos como Assunto , Modelos Animais de Doenças , Progressão da Doença , Humanos , Estadiamento de Neoplasias , Neoplasias/diagnóstico , Neoplasias/etiologia , Prognóstico , Resultado do Tratamento
2.
Medicine (Baltimore) ; 98(34): e16966, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441902

RESUMO

The importance of optimal blood pressure control for preventing or reducing the impairment of vascular and cognitive functions is well known. However, the reversibility of early alterations in vascular and cognitive functions through antihypertensive agents is under-investigated. In this study, we evaluated the influence of 3 months of angiotensin-converting enzyme (ACE) inhibition treatment on the morphological and functional arterial wall and cognitive performance changes in 30 newly diagnosed primary hypertensive patients.Common carotid intima-media thickness (IMT) and brachial artery flow-mediated dilatation (FMD) were detected by ultrasonography. Arterial stiffness indicated by augmentation index (AIx) and pulse wave velocity (PWV) was assessed by arteriography. Cognitive functions were assessed by neuropsychological examination.The executive function overall score was significantly higher at 3-month follow-up than at baseline (median, 0.233 (IQR, 0.447) vs -0.038 (0.936); P = .001). Three-month ACE inhibition did not produce significant improvement in IMT, FMD, AIx and PWV values. Significant negative associations were revealed between IMT and complex attention (r = -0.598, P = .0008), executive function (r = -0.617, P = .0005), and immediate memory (r = -0.420, P = .026) overall scores at follow-up. AIx had significant negative correlations with complex attention (r = -0.568, P = .001), executive function (r = -0.374, P = .046), and immediate memory (r = -0.507, P = .005). PWV correlated significantly and negatively with complex attention (r = -0.490, P = .007).Timely and effective antihypertensive therapy with ACE inhibitors has significant beneficial effects on cognitive performance in as few as 3 months. Early ACE inhibition may have an important role in the reversal of initial impairments of cognitive function associated with hypertension-induced vascular alterations.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Cognição/efeitos dos fármacos , Rigidez Vascular/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Adulto , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Artéria Braquial/diagnóstico por imagem , Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Feminino , Seguimentos , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
3.
Plant Foods Hum Nutr ; 74(3): 405-413, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31273642

RESUMO

The aim of this work was to evaluate the ability of broken rice, an underutilized industrial by-product, as a potential functional and health promoting ingredient. With this purpose, the ability to inhibit the angiotensin converting enzyme and renin of a rice protein hydrolyzate (RPH) obtained from a high-protein variety of broken rice (var. Nutriar FCAyF) was analyzed (IC50 = 0.87 and 2.7 mg/mL, respectively). RPH was separated by gel permeation chromatography and in a second purification step by RP-HPLC. The sequence of antihypertensive peptides presented in two RP-HPLC fractions was analyzed. Peptides capable of interacting with the active sites of both enzymes were identified. In this study, we demonstrate that the hydrolysis treatment improves functional and biological properties of rice proteins. Protein preparations obtained from a by-product of rice industry, such as broken rice, are a promising ingredient with potentially good biological properties.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Hipertensivos/isolamento & purificação , Oryza/química , Peptídeos/isolamento & purificação , Renina/antagonistas & inibidores , Anti-Hipertensivos/farmacologia , Cromatografia Líquida de Alta Pressão , Promoção da Saúde , Hidrólise , Simulação de Acoplamento Molecular , Peptídeos/farmacologia , Peptidil Dipeptidase A/metabolismo , Proteínas de Plantas/antagonistas & inibidores , Proteínas de Plantas/metabolismo , Renina/metabolismo
4.
Food Chem ; 299: 124985, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31279127

RESUMO

Dietary protein peptides from quinoa yoghurt beverage (QYB) fermented with probiotic lactic acid bacteria strains play a protective role against diabetes and hypertension. In this study, the α-glucosidase and ACE inhibitory activities of germination-based protein hydrolysates of QYB were investigated. All protein hydrolysates exhibited a dose and strain-dependent inhibition on the enzymes. The inhibition of α-glucosidase was the highest in QLCSY13 (IC50 = 8.86 mg/mL), while ACE inhibition was the highest in QLCZ (IC50 = 0.03 mg/mL). Overall, QLCSY13 had the highest inhibitory activities, which was ascribed to its relatively higher amino acid contents and hydrophobicity. In addition, the ACE and α-glucosidase inhibitory activities of peptide fractions identified by RP-HPLC were 127 ±â€¯4.29 mg/mL and 10.39 ±â€¯4.73 mg/mL respectively. Among the potent inhibitory peptide sequences identified, both LAHMIVAGA and VAHPVF significantly had α-glucosidase and ACE inhibitory activities. Consequently, dietary protein peptides present in QYB had anti-hypertensive and anti-diabetic potentials.


Assuntos
Bebidas/microbiologia , Lactobacillus casei/metabolismo , Peptidil Dipeptidase A/metabolismo , Hidrolisados de Proteína/farmacologia , Iogurte/microbiologia , alfa-Glucosidases/metabolismo , Sequência de Aminoácidos , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Fermentação , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/farmacologia , Hidrolisados de Proteína/química
5.
Artigo em Chinês | MEDLINE | ID: mdl-31245959

RESUMO

OBJECTIVE: To investigate the correlation between the carotid artery plaque and the change of plasma aldosterone level related indexes during captopril challenge test. METHODS: The patients with hypertension were enrolled as research objects and the captopril challenge test were carried out when they were hospitalized to screen the cause of hypertension. There were intact carotid artery duplex ultrasonography diagnostic data in them (83 cases). They were divided into the plaque group(57 cases) with carotid artery plaque and no plaque group( 26 cases) without carotid artery plaque according to the carotid artery duplex ultrasonography diagnostic data. The correlation between the carotid artery plaque and the changes of aldosterone concentration, renin activity and aldosterone to renin activity ratio(ARR) in two groups were analyzed. RESULTS: The detection rate of carotid artery plaque was 68.67%. Compare with no plaque group, the patients in plaque group were elder and the level of apolipoprotein A1,(APOA1) was lower (all P<0.05). The ARR difference value before and after captopril challenge test was lower ( P<0.05).The aldosterone difference value and the renin activity difference value before and after captopril challenge test were higher in plaque group (all P<0.05).The aldosterone difference value and the renin activity difference value were positive in plaque group and were negative in no plaque group. The difference value of the ARR was negative in plaque group and was positive in no plaque group. Logistic regression analysis showed that the age, the difference value of ARR and the aldosterone before and after captopril challenge test could be associated independently with carotid artery plaque occurrence after excluding gender difference and other factors. CONCLUSION: The detection rate of carotid artery plaque was high among hospitalized patients with hypertension, the difference value of ARR and the aldosterone before and after captopril challenge test could be associated independently with carotid artery plaque occurrence.


Assuntos
Aldosterona , Inibidores da Enzima Conversora de Angiotensina , Captopril , Estenose das Carótidas , Hipertensão , Aldosterona/sangue , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Captopril/farmacologia , Estenose das Carótidas/tratamento farmacológico , Humanos , Hipertensão/tratamento farmacológico , Pacientes Internados , Renina
6.
Toxicol Lett ; 313: 30-41, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31181250

RESUMO

The hedgehog (HH) signaling pathway plays an important role in lung development, but its significance in silicosis is unclear. We showed that in human coal pneumoconiosis autopsy specimens, Sonic Hedgehog (SHH) and the Glioma-associated oncogene homolog transcription factors family (GLI) 1 proteins were up-regulated, whereas Patch-1 (PTC) was down-regulated. The protein levels of SHH, smoothened (SMO), GLI1, GLI2, α-smooth muscle actin (α-SMA) and collagen type Ⅰ (Col Ⅰ) were also elevated gradually in the bronchoalveolar lavage fluid (BALF) of different stages of coal pneumoconiosis patients, dynamic silica-inhalation rat lung tissue and MRC-5 cells induced by Ang II at different time points, whereas the PTC and GLI3 levels were diminished gradually. Ac-SDKP, an active peptide of renin-angiotensin system (RAS), is an anti-fibrotic tetrapeptide. Targeting RAS axis also has anti-silicotic fibrosis effects. However, their roles on the HH pathway are still unknown. Here, we reported that Ac-SDKP + Captopril, Ac-SDKP, Captopril, or Ang (1-7) could alleviate silicotic fibrosis and collagen deposition, as well as improve the lung functions of silicotic rat. These treatments decreased the expression of SHH, SMO, GLI1, GLI2, α-SMA, and Col Ⅰ and increased the expression of PTC and GLI3 on both the silicotic rat lung tissue and MRC-5 cells induced by Ang II. We also reported that Ang II may promote myofibroblast differentiation via the GLI1 transcription factor and independently of the SMO receptor.


Assuntos
Angiotensina II/farmacologia , Angiotensina I/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Captopril/farmacologia , Diferenciação Celular/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Miofibroblastos/efeitos dos fármacos , Oligopeptídeos/farmacologia , Fragmentos de Peptídeos/farmacologia , Fibrose Pulmonar/prevenção & controle , Sistema Renina-Angiotensina/efeitos dos fármacos , Silicose/prevenção & controle , Adulto , Idoso , Animais , Antracose/metabolismo , Antracose/patologia , Linhagem Celular , Colágeno/metabolismo , Modelos Animais de Doenças , Feminino , Proteínas Hedgehog/metabolismo , Humanos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Silicose/metabolismo , Silicose/patologia
7.
Yonsei Med J ; 60(7): 679-686, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31250582

RESUMO

PURPOSE: Statins, metformin, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) have been suggested for treating age-related macular degeneration (AMD) due to their pleiotropic effects. Therefore, we investigated whether these drugs prevent AMD. MATERIALS AND METHODS: We conducted a nested case-control study using the Korean National Health Insurance Service database. Using risk-set sampling of age, sex, cohort entry date, and follow-up duration, we identified incident patients with AMD and 10 matching controls in cohorts with diabetes mellitus or cardiovascular diseases. Exposure was assessed within one year before the index date using patient prescription records. We conducted conditional logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between cardiovascular medications and AMD. RESULTS: Our study included 2330 cases and 23278 controls from a cohort of 231274 patients. The ORs (95% CI) for AMD occurrence in users prescribed with statins, metformin, ACE inhibitors, and ARBs were 1.12 (0.94-1.32), 1.15 (0.91-1.45), 0.90 (0.61-1.34), and 1.21 (1.05-1.39), respectively. A duration-response was not observed. CONCLUSION: Statins, metformin, ACE inhibitors, and ARBs did not inhibit AMD in elderly patients. The absence of a duration-response supports the lack of a causal relationship.


Assuntos
Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Degeneração Macular/tratamento farmacológico , Metformina/farmacologia , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Modelos Logísticos , Masculino , Metformina/uso terapêutico
8.
Malar J ; 18(1): 213, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234939

RESUMO

BACKGROUND: Malaria represents a worldwide medical emergency affecting mainly poor areas. Plasmodium parasites during blood stages can release kinins to the extracellular space after internalization of host kininogen inside erythrocytes and these released peptides could represent an important mechanism in liver pathophysiology by activation of calcium signaling pathway in endothelial cells of vertebrate host. Receptors (B1 and B2) activated by kinins peptides are important elements for the control of haemodynamics in liver and its physiology. The aim of this study was to identify changes in the liver host responses (i.e. kinin receptors expression and localization) and the effect of ACE inhibition during malaria infection using a murine model. METHODS: Balb/C mice infected by Plasmodium chabaudi were treated with captopril, an angiotensin I-converting enzyme (ACE) inhibitor, used alone or in association with the anti-malarial chloroquine in order to study the effect of ACE inhibition on mice survival and the activation of liver responses involving B1R and B2R signaling pathways. The kinin receptors (B1R and B2R) expression and localization was analysed in liver by western blotting and immunolocalization in different conditions. RESULTS: It was verified that captopril treatment caused host death during the peak of malaria infection (parasitaemia about 45%). B1R expression was stimulated in endothelial cells of sinusoids and other blood vessels of mice liver infected by P. chabaudi. At the same time, it was also demonstrated that B1R knockout mice infected presented a significant reduction of survival. However, the infection did not alter the B2R levels and localization in liver blood vessels. CONCLUSIONS: Thus, it was observed through in vivo studies that the vasodilation induced by plasma ACE inhibition increases mice mortality during P. chabaudi infection. Besides, it was also seen that the anti-malarial chloroquine causes changes in B1R expression in liver, even after days of parasite clearance. The differential expression of B1R and B2R in liver during malaria infection may have an important role in the disease pathophysiology and represents an issue for clinical treatments.


Assuntos
Regulação da Expressão Gênica , Fígado/fisiopatologia , Malária/fisiopatologia , Receptor B1 da Bradicinina/genética , Receptor B2 da Bradicinina/genética , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Captopril/farmacologia , Cloroquina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Plasmodium chabaudi , Receptor B1 da Bradicinina/metabolismo , Receptor B2 da Bradicinina/metabolismo
9.
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
10.
Molecules ; 24(9)2019 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-31060345

RESUMO

The multivesicular liposome (MVL) provides a potential delivery approach to avoid the destruction of the structure of drugs by digestive enzymes of the oral cavity and gastrointestinal system. It also serves as a sustained-release drug delivery system. In this study, we aimed to incorporate a water-soluble substance into MVLs to enhance sustained release, prevent the destruction of drugs, and to expound the function of different components and their mechanism. MVLs were prepared using the spherical packing model. The morphology, structure, size distribution, and zeta potential of MVLs were examined using an optical microscope (OM), confocal microscopy (CLSM), transmission electron cryomicroscope (cryo-EM) micrograph, a Master Sizer 2000, and a zeta sizer, respectively. The digestion experiment was conducted using a bionic mouse digestive system model in vitro. An in vitro release and releasing mechanism were investigated using a dialysis method. The average particle size, polydispersity index, zeta potential, and encapsulation efficiency are 47.6 nm, 1.880, -70.5 ± 2.88 mV, and 82.00 ± 0.25%, respectively. The studies on the controlled release in vitro shows that MVLs have excellent controlled release and outstanding thermal stability. The angiotensin I-converting enzyme (ACE) inhibitory activity of ACE-inhibitory peptide (AP)-MVLs decreased only 2.84% after oral administration, and ACE inhibitory activity decreased by 5.03% after passing through the stomach. Therefore, it could serve as a promising sustained-release drug delivery system.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Arachis/metabolismo , Sistema Digestório/química , Peptídeos/farmacologia , Administração Oral , Inibidores da Enzima Conversora de Angiotensina/química , Animais , Preparações de Ação Retardada , Composição de Medicamentos , Estabilidade de Medicamentos , Humanos , Lipossomos , Camundongos , Modelos Biológicos , Tamanho da Partícula , Peptídeos/química , Peptidil Dipeptidase A , Solubilidade
11.
Mar Drugs ; 17(3)2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-30934583

RESUMO

Plastid proteins are one of the main components in red algae. In order to clarify the angiotensin I converting enzyme (ACE) inhibitory peptides from red alga Palmaria sp. (Japan), we determined the plastid genome sequence. The genome possesses 205 protein coding genes, which were classified as genetic systems, ribosomal proteins, photosystems, adenosine triphosphate (ATP) synthesis, metabolism, transport, or unknown. After comparing ACE inhibitory peptides between protein sequences and a database, photosystems (177 ACE inhibitory peptides) were found to be the major source of ACE inhibitory peptides (total of 751). Photosystems consist of phycobilisomes, photosystem I, photosystem II, cytochrome complex, and a redox system. Among them, photosystem I (53) and II (51) were the major source of ACE inhibitory peptides. We found that the amino acid sequence of apcE (14) in phycobilisomes, psaA (18) and psaB (13) in photosystem I, and psbB (11) and psbC (10) in photosystem II covered a majority of bioactive peptide sequences. These results are useful for evaluating the bioactive peptides from red algae.


Assuntos
Rodófitas/genética , Sequência de Aminoácidos , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Simulação por Computador , Genomas de Plastídeos , Fases de Leitura Aberta , Peptídeos/metabolismo , Peptídeos/farmacologia , Rodófitas/metabolismo , Sequenciamento Completo do Genoma
12.
Toxicol Lett ; 309: 42-50, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30940551

RESUMO

Recent epidemiological studies have found that diisononyl phthalate (DINP) is associated with an increase in blood pressure. However, this correlation had not been clarified, nor has the underlying mechanism been characterized. In this study, C57/BL6 mice were exposed to DINP doses of 0.15 mg/kg/day, 1.5 mg/kg/day or 15 mg/kg/day for 6 weeks. Dexamethasone (DEXA) was used to build the hypertension model. After DINP exposure and 1 mg/kg/day DEXA treatment, the levels of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP) and heart rate (HR) were determined, and any histopathological changes in hypertension targeted organs of the mice were investigated. The results suggest that DINP exposure and DEXA treatment induced marked increases in SBP, DBP, and MBP, and that 15 mg/kg/day DINP exposure could also increase the HR level. Along with the blood pressure increase, DINP exposure induced pathological changes to the heart, aorta, and kidney. To explore the underlying mechanism, we measured the expression of angiotensin converting enzyme (ACE), angiotensin-II type 1 receptor (AT1R) and endothelial nitric oxide synthase (eNOS) in the aorta, as well as the nitric oxide (NO) concentration in serum. The data suggest that DINP exposure and DEXA treatment enhance the expression of ACE and AT1R, and inhibit eNOS expression and NO production. Interestingly, treatment with 5 mg/kg/day ACE inhibitor (ACEI) alleviated the increase in blood pressure induced by DINP exposure and DEXA treatment. These findings expand our understanding of how DINP exposure impacts the development of hypertension, and elucidates the underlying mechanisms.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Óxido Nítrico/antagonistas & inibidores , Peptidil Dipeptidase A/fisiologia , Ácidos Ftálicos/toxicidade , Receptor Tipo 1 de Angiotensina/fisiologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Dexametasona/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo III/fisiologia
13.
J Food Sci ; 84(5): 1170-1179, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30997940

RESUMO

High blood pressure can lead to cardiovascular diseases. The objective of this work was to obtain protein hydrolysates with antihypertensive potential from chia oil industry meal byproduct. Chia seed protein isolates (CPIs) were obtained from chia seed meal byproduct. CPI was hydrolyzed using different proteases (alcalase, pepsin, trypsin, and α-chymotrypsin) and their biological potential was evaluated using in vitro and in silico approaches. Chia seed pepsin protein hydrolysate showed the highest angiotensin-converting enzyme inhibition potential IC50 of 0.128 mg/mL (P < 0.05) compared to the rest of hydrolysates. Peptide sequence LIVSPLAGRL presented the lowest predicted binding energy and highest inhibition potential (-9.5 kcal/mol) compared to other sequenced peptides and positive controls (captopril and lisinopril). Chia peptides showed potential to block angiotensin-converting enzyme by interacting with its catalytic site. Chia seed oil industry meal byproduct could be used as an inexpensive source of protein and bioactive peptides with antihypertensive potential. PRACTICAL APPLICATION: This research shows an upcycling alternative for chia oil industry byproduct. Chia meal is a rich source of protein and can be used to generate bioactive peptides with antihypertensive potential. Chia protein isolate was obtained from chia meal and hydrolyzed using different enzymes, pepsin showed the highest antihypertensive potential. Chia meal waste could be a low-cost source of protein and protein hydrolysates that could be used as a food ingredient with antihypertensive potential.


Assuntos
Inibidores da Enzima Conversora de Angiotensina , Anti-Hipertensivos , Pepsina A , Peptidil Dipeptidase A , Proteínas de Plantas , Salvia/química , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Hipertensivos/química , Anti-Hipertensivos/metabolismo , Anti-Hipertensivos/farmacologia , Domínio Catalítico , Pepsina A/química , Pepsina A/metabolismo , Pepsina A/farmacologia , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Proteínas de Plantas/farmacologia , Hidrolisados de Proteína/química , Hidrolisados de Proteína/metabolismo , Hidrolisados de Proteína/farmacologia
14.
Int J Mol Sci ; 20(6)2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-30934634

RESUMO

In this study, we combined enzymatic hydrolysis and lactic acid fermentation to generate an antihypertensive product. Soybean protein isolates were first hydrolyzed by Prozyme and subsequently fermented with Lactobacillus rhamnosus EBD1. After fermentation, the in vitro angiotensin-converting enzyme (ACE) inhibitory activity of the product (P-SPI) increased from 60.8 ± 2.0% to 88.24 ± 3.2%, while captopril (a positive control) had an inhibitory activity of 94.20 ± 5.4%. Mass spectrometry revealed the presence of three potent and abundant ACE inhibitory peptides, PPNNNPASPSFSSSS, GPKALPII, and IIRCTGC in P-SPI. Hydrolyzing P-SPI with gastrointestinal proteases did not significantly affect its ACE inhibitory ability. Also, oral administration of P-SPI (200 mg/kg body weight) to spontaneous hypertensive rats (SHRs) for 6 weeks significantly lowered systolic blood pressure (-19 ± 4 mm Hg, p < 0.05) and controlled body weight gain relative to control SHRs that were fed with physiological saline. Overall, P-SPI could be used as an antihypertensive functional food.


Assuntos
Anti-Hipertensivos/farmacologia , Hidrolisados de Proteína/farmacologia , Proteínas de Soja/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Fermentação/efeitos dos fármacos , Trato Gastrointestinal/enzimologia , Coelhos , Suínos , Sístole/efeitos dos fármacos , Fatores de Tempo , Ganho de Peso/efeitos dos fármacos
15.
J Dairy Sci ; 102(7): 5913-5921, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31030932

RESUMO

Angiotensin-converting enzyme inhibitory peptides were isolated and identified from milk fermented using Lactobacillus delbrueckii QS306. The peptide with the highest angiotensin-converting enzyme inhibitory activity (C5) was purified using ultrafiltration with 10 and 3 kDa molecular mass cut-off membranes, Sephadex G-15 (Sigma-Aldrich, St. Louis, MO) gel filtration chromatography, reversed-phase HPLC, and Orbitrap Elite (Thermo Fisher Scientific Inc., Waltham, MA) liquid chromatography-tandem mass spectrometry. We obtained peptide LPYPY by microbial fermentation, which was derived from κ-casein f (AA 77-81). We synthesized LPYPY using an Fmoc solid-phase synthesis method and explored the secondary structure of the pentapeptide. The half maximal inhibitory concentration for the angiotensin-converting enzyme inhibitory activity of LPYPY was 12.87 µg/mL. The results provide additional information for ongoing research and the development of functional foods having antihypertensive effects.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/análise , Proteínas de Bactérias/análise , Lactobacillus delbrueckii/química , Leite/química , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Anti-Hipertensivos/análise , Anti-Hipertensivos/farmacologia , Fermentação , Leite/microbiologia , Peptídeos/análise
16.
J Biochem ; 166(3): 223-230, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31004484

RESUMO

Vinegar soaked black soybean is a traditional Chinese food widely used for the treatment of hypertension. While its pharmacodynamic substance was not fully unveiled. It contained abundant glutelin, thus the purpose of this study was to obtain potent antihypertensive peptides from vinegar soaked black soybean. Black soybean was soaked with vinegar and then glutelin was first catalyzed by alcalase. Ultrafiltration, ion exchange chromatography and reversed-phase high performance liquid chromatography were sequentially applied to separate and purify the angiotensin-I converting enzyme (ACE) inhibitory peptides from glutelin hydrolysates. As a result, the fraction L1-4 with the highest ACE inhibitory activity (83.41%) at the final concentration of 0.01 mg/ml was obtained and five peptides were then identified. These peptides were further optimized by virtual screening combining with in silico proteolysis. Finally, a novel tetrapeptide Phe-Gly-Ser-Phe (FGSF) was obtained. FGSF exhibited high in vitro ACE inhibitory activity (IC50 = 117.11 µM) and in vivo hypotensive effect which maximally reduced systolic blood pressure of 21.95 mmHg at 20 mg/kg body weight in spontaneously hypertensive rats. Our study demonstrated that FGSF derived from vinegar soaked black soybean might be used as a promising ingredient for pharmaceuticals against hypertension and its related diseases.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Hipertensivos/farmacologia , Glutens/química , Hipertensão/tratamento farmacológico , Oligopeptídeos/farmacologia , Soja/química , Ácido Acético/química , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/isolamento & purificação , Animais , Anti-Hipertensivos/química , Anti-Hipertensivos/isolamento & purificação , Relação Dose-Resposta a Droga , Glutens/isolamento & purificação , Hipertensão/metabolismo , Masculino , Simulação de Acoplamento Molecular , Oligopeptídeos/química , Oligopeptídeos/isolamento & purificação , Peptidil Dipeptidase A/metabolismo , Ratos , Ratos Endogâmicos SHR , Relação Estrutura-Atividade
17.
Mar Drugs ; 17(4)2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-30935056

RESUMO

A protein extract was generated from the macroalga Ulva lactuca, which was subsequently hydrolysed using the food-grade enzyme papain and angiotensin-converting Enzyme I and renin inhibitory peptides identified using a combination of enrichment strategies employing molecular weight cutoff filtration and mass spectrometry analysis. The generated hydrolysates with the most promising in vitro activity were further purified using preparative RP-HPLC and characterised. The 1 kDa hydrolysate (1 kDa-UFH), purified and collected by preparative RP-HPLC at minutes 41‒44 (Fr41‒44), displayed statistically higher ACE-I inhibitory activities ranging from 96.91% to 98.06%. A total of 48 novel peptides were identified from these four fractions by LC-MS/MS. A simulated gastrointestinal digestion of the identified peptide sequences was carried out using in silico enzyme cleavage simulation tools, resulting in 86 peptide sequences that were further assessed for their potential activity, toxicity and allergenicity using multiple predictive approaches. All the peptides obtained in this study were predicted to be non-toxic. However, 28 out of the 86 novel peptides released after the in silico gastrointestinal digestion were identified as potential allergens. The potential allergenicity of these peptides should be further explored to comply with the current labelling regulations in formulated food products containing U. lactuca protein hydrolysates.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/metabolismo , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Oligopeptídeos/metabolismo , Oligopeptídeos/farmacologia , Hidrolisados de Proteína/farmacologia , Ulva/metabolismo , Alérgenos/farmacologia , Sequência de Aminoácidos , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/isolamento & purificação , Anti-Hipertensivos/farmacologia , Simulação por Computador , Humanos , Hidrólise , Oligopeptídeos/química , Oligopeptídeos/isolamento & purificação , Hidrolisados de Proteína/química , Hidrolisados de Proteína/isolamento & purificação , Alga Marinha/química , Ulva/química , Ulva/citologia
18.
Biomed Pharmacother ; 114: 108660, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30974387

RESUMO

Dendritic cells (DCs) play a complex role in the progression of myocardial infarction (MI). The impact of angiotensin-converting enzyme (ACE) inhibitor therapy, partly via affecting DCs maturation and recruitment, was tested on a MI mouse model. Furthermore, the cardioprotective effects of ACEI were enhanced through attenuating migration of DCs from the spleen into peripheral circulation, thereby inhibiting DCs maturation and tissue inflammation. ACEI repress DCs immune inflammatory response through down-regulating DCs maturation surface markers and regulating inflammatory cytokines, which led to a higher survival rate, improved function and remodeling through decreased inflammatory response after MI. However, inhibition of AT2R activation, resulted in a reduction of ACEI effects on DCs. The potent anti-inflammatory effect of ACEI can partially be attributed to its impact on DCs through activation of AT2R, which may provide a new target mechanism for ACEI therapy after MI.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Células Dendríticas/efeitos dos fármacos , Coração/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Receptor Tipo 2 de Angiotensina/metabolismo , Remodelação Ventricular/efeitos dos fármacos , Antagonistas de Receptores de Angiotensina/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Taxa de Sobrevida
19.
Pharmacol Rep ; 71(2): 306-310, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30826571

RESUMO

BACKGROUND: We hypothesized that renin-angiotensin system and neprilysin (NEP) inhibition can modulate the nociceptive parameters on hypertensive rats. The aim of this study is to assess the preventive and therapeutic effects of ramipril and sacubitril on the pain hypersensitivities, and their interaction mechanisms with high blood pressure. METHODS: Antinociceptive effects of ramipril and sacubitril were compared with those of diclofenac. Threshold of pain assesments were recorded before drugs administration. After a 18 days treatment, normotensive and dexamethasone-induced hypertensive rats were evaluated on thermal hyperalgesia and mechanical allodynia tests. Blood pressure of rats were verified by mean arterial pressure measurement. RESULTS: Hypertensive rats showed significantly high pain threshold on thermal plantar test compared to that of normotensives. Among hypertensive rats, pain hypersensitivity was lowest in diclofenac group, followed by sacubitril group, while ramipril caused increased thermal and mechanical hypersensitivities. CONCLUSION: We found that NEP inhibition may play a role in nociception in hypertensive rats. NEP inhibitors may be suitable choice for the management of hypertension and pain because of their therapeutic and preventive effects on nociception and arterial blood pressure.


Assuntos
Aminobutiratos/farmacologia , Hipertensão/tratamento farmacológico , Dor/tratamento farmacológico , Ramipril/farmacologia , Tetrazóis/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Dexametasona/toxicidade , Modelos Animais de Doenças , Hipertensão/complicações , Masculino , Neprilisina/metabolismo , Dor/etiologia , Limiar da Dor/efeitos dos fármacos , Peptidil Dipeptidase A/efeitos dos fármacos , Peptidil Dipeptidase A/metabolismo , Ratos , Ratos Wistar , Sistema Renina-Angiotensina/efeitos dos fármacos
20.
Artigo em Inglês | MEDLINE | ID: mdl-30875817

RESUMO

Cardiovascular diseases (CVDs) have become the leading cause of disability and death worldwide, particularly in low- and middle-income countries. Hypertension, a major cause of CVD progression, is widely attributable to genetic, behavioral, and environmental risk factors. Among the genetic reasons, angiotensin II enzyme, produced as a result of abnormal functioning of the renin⁻angiotensin system, is reported as the foremost cause of hypertension. A cascade of genes, including those encoding for WNK kinases (WNK1 and WNK4), Bp1, Bp2, angiotensinogen, and other enzymes, is involved in the conversion of angiotensin I to angiotensin II. However, the angiotensin-converting enzyme (ACE) plays a crucial role in this pathway. Therefore, ACE could be a potential therapeutic target in regulating the conversion of angiotensin I to angiotensin II and eventually controlling hypertension. In this study, a molecular docking-based approach was utilized for identifying and evaluating potential inhibitors of ACE present in herbs, other natural sources, and synthetic sources, on the basis of these compounds' binding affinities and other physicochemical features. In addition, the suitability of these inhibitors as drugs for biological systems, considering their adsorption, distribution, metabolism, and excretion (ADME), was predicted using Lipinski's rule. In conclusion, our study provides a novel and clearer insight into the interaction properties of known putative inhibitors of ACE.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Hipertensivos/farmacologia , Hipertensão/tratamento farmacológico , Peptidil Dipeptidase A/metabolismo , Inibidores da Enzima Conversora de Angiotensina/classificação , Humanos , Simulação de Acoplamento Molecular
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