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1.
J Appl Oral Sci ; 27: e20180574, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31596365

RESUMO

OBJECTIVES: Hypertension is one of the main causes of premature death in the world; also, it is associated with several bone alterations. Preclinical studies have demonstrated delayed alveolar bone healing in hypertensive rats. However, losartan has been favorable for consolidation of bone grafts and reduction in active periodontitis. Therefore, losartan is suggested to be effective in bone formation stages, as well as in the synthesis of matrix proteins and mineralization. To evaluate the alveolar bone dynamics in hypertensive rats treated with losartan by laser confocal microscopy and histological analysis. METHODOLOGY: Thirty-two rats, 16 spontaneously hypertensive rats (SHR) and 16 Wistar albinus rats, treated or not with losartan (30 mg/kg/day) were used. Calcein fluorochrome at 21 days and alizarin red fluorochrome at 49 days were injected in rats (both 20 mg/kg). The animals were submitted to euthanasia 67 days after treatment, and then the right maxilla was removed for laser confocal microscopy analysis and the left maxilla for histological analysis. RESULTS: This study showed a greater calcium marking in normotensive animals treated with losartan in relation to the other groups. Laser confocal microscopy parameters showed higher values of bone volume formed, mineralized surface, active surface of mineralization and bone formation rate in normotensive animals treated with losartan. However, a smaller mineralized surface was observed in all hypertensive animals. CONCLUSION: Losartan can improve bone mineralization parameters under normal physiological conditions, but the same anabolic effect does not occur under hypertension.


Assuntos
Processo Alveolar/efeitos dos fármacos , Processo Alveolar/fisiopatologia , Anti-Hipertensivos/farmacologia , Hipertensão/fisiopatologia , Losartan/farmacologia , Processo Alveolar/patologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Calcificação Fisiológica/efeitos dos fármacos , Fluoresceínas/análise , Masculino , Microscopia Confocal , Osteogênese/efeitos dos fármacos , Ratos Endogâmicos SHR , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Tempo
2.
Rev Med Suisse ; 15(662): 1608-1613, 2019 Sep 11.
Artigo em Francês | MEDLINE | ID: mdl-31508912

RESUMO

After numerous years of research and development of effective anti-hypertensive drugs, it is regrettable to note that less than half of hypertensive patients reach the blood pressure targets that are known to reduce their cardiovascular risks and mortality. Poor adherence to treatment is one of the main causes of insufficient blood pressure control. Furthermore, non-adherence to anti-hypertensive therapy correlates with higher risks of cardiovascular events. The objective of health professionals is to identify non adherent patients and to offer them appropriate solutions to support their treatment self-management. Innovative approaches like using electronic pillboxes combined with an interprofessional medication adherence support program should allow a more appropriate and effective care.


Assuntos
Anti-Hipertensivos , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipertensão/psicologia , Adesão à Medicação , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Humanos , Hipertensão/fisiopatologia
3.
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
4.
Toxicol Lett ; 315: 9-13, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31408697

RESUMO

Cytochrome P450 mediated metabolism is the rate-limiting step of elimination for many drugs. CYP3A4 is the most abundant hepatic isoform and CYP3A4/5 metabolize the largest fraction of drugs. Pharmacogenetic studies have not been able to characterize population variability in CYP3A4 activity because few variant alleles associated with aberrant enzyme activity have been found. Substrate probes such as midazolam and testosterone have been utilized in-vivo and in-vitro to determine catalytic activity of these enzymes, but they suffer from several limitations. Eplerenone, an aldosterone antagonist, is also metabolized by CYP3A enzymes, and it has the potential to be an excellent substrate probe for CYP3A4/5. Eplerenone's primary metabolite, 6 beta-hydroxyeplerenone is formed preferentially via CYP3A4, however, the relative contribution of CYP3A5 to the 21-hydroxyeplerenone metabolite formation is unknown. Through in-vitro microsomal incubations with recombinant CYP3A4 and CYP3A5 enzymes, we identified their relative contributions to 21-hydroxyeplerenone metabolism. The 21-hydroxy metabolite is formed preferentially via CYP3A5 Vmax/KM (3.3) versus CYP3A4 Vmax/KM (1.9). Based on these findings, eplerenone has the potential to serve as an in-vivo substrate probe for CYP3A4 by monitoring 6-beta-hydroxy metabolite formation as well as CYP3A4/5 by monitoring 21-hydroxy metabolite formation.


Assuntos
Anti-Hipertensivos/metabolismo , Anti-Hipertensivos/farmacologia , Citocromo P-450 CYP3A/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/farmacologia , Eplerenona/metabolismo , Eplerenona/farmacologia , Hipertensão/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Humanos , Microssomos/metabolismo
5.
Life Sci ; 234: 116792, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31465733

RESUMO

AIMS: Assisted reproductive technologies (ART) have been widely used to treat infertility, which may impact on fetuses and offspring. This study investigated the effects of in vitro fertilization-embryo transfer (IVF-ET) on angiotensin II (AII)-mediated vasoconstrictions in umbilical cord vein, and explored possible reprogrammed methylation mechanism. MATERIALS AND METHODS: Human umbilical cords were randomly divided into ordinary pregnancy and IVF-ET pregnancy. Vascular studies with AII as well as its specific receptor antagonists losartan and PD123,319 were conducted. Real-time quantitative PCR, Western blotting, and methylation analysis by bisulfite sequencing were performed with the cord vessel samples. KEY FINDINGS: In IVF-ET group, the maximal response to AII in umbilical vessels was significantly greater than that in the ordinary pregnancy. Using losartan and PD123,319, angiotensin receptor subtype 1 (AT1R) was found mainly responsible for the enhanced contraction in the umbilical vein of IVF-ET pregnancy. Decreased mRNA expression of DNMT3A was found in umbilical vein of IVF-ET group. Hypomethylation of the AGTR1 gene (gene encoding AT1R) in the umbilical veins of the IVF group was found. The data suggested that the IVF-ET treatments altered AII-mediated vasoconstrictions in umbilical veins, which could be partially attributed to the increased expression of AT1R. SIGNIFICANCE: The hypo-methylation of the AGTR1 gene caused by IVF-ET might play important roles in altered vasoconstrictions, impacting on cardiovascular systems in the long run.


Assuntos
Angiotensina II/metabolismo , Metilação de DNA , Transferência Embrionária/métodos , Fertilização In Vitro/métodos , Receptor Tipo 1 de Angiotensina/genética , Cordão Umbilical/irrigação sanguínea , Vasoconstrição , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 2 de Angiotensina II/farmacologia , Anti-Hipertensivos/farmacologia , Transferência Embrionária/efeitos adversos , Feminino , Fertilização In Vitro/efeitos adversos , Humanos , Imidazóis/farmacologia , Losartan/farmacologia , Gravidez , Piridinas/farmacologia , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/farmacologia
6.
Expert Opin Ther Pat ; 29(10): 793-803, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31462124

RESUMO

Introduction: Elevated intraocular pressure (IOP) is the most prevalent risk factor for glaucoma. Prostaglandin analogs are a first-line therapy for glaucoma due to their ability to reduce IOP, once-daily dosing, efficacy, and minimal side-effect profile. Many compounds targeting different PG receptors have been developed in the last years, some of them being in clinical use. Latanoprost, Bimatoprost, Travoprost, and Tafluprost are clinically used as antiglaucoma drugs and act as agonists of the PGF2α receptor. The inability to fully understand the mechanism of action of clinically used PGF2α analogs is thus a strong driver for additional research into the mechanism of action of ocular hypotensive drugs belonging to this class of pharmacological agents. Areas covered: This review explores the last 5 years (2013-2018), where many patents describing new compounds acting on different prostaglandin receptors, and mainly targeting EP1-4 and FP receptors, were released. Expert opinion: To date, there has been a growing awareness over recent years of the therapeutic use of novel derivatives as new antiglaucoma pharmaceutical products. Patents involved in discovering new approaches and new molecules for the treatment of glaucoma diseases encouraged the scientific community to increase the variety of drugs available for the treatment of ocular diseases.


Assuntos
Glaucoma/tratamento farmacológico , Prostaglandinas Sintéticas/farmacologia , Receptores de Prostaglandina/agonistas , Animais , Anti-Hipertensivos/farmacologia , Desenvolvimento de Medicamentos , Glaucoma/patologia , Humanos , Pressão Intraocular/efeitos dos fármacos , Patentes como Assunto , Fatores de Risco
7.
DNA Cell Biol ; 38(10): 1134-1142, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31433203

RESUMO

Diabetes mellitus is a complicated metabolic disease characterized by hyperglycemia. Diabetic nephropathy (DN) is a progressive kidney disease, which results in mortality in diabetic patients. The present study was designed to investigate the effect of applying spironolactone (S), captopril (C), and their combination (S+C) on some renal performance indices and microRNAs' (miRNAs) expression. A total of 35 two-month-old male Wistar rats were provided for the study. Intraperitoneal injection of freshly dissolved streptozotocin (60 mg/kg) in cold citrate buffer was used to induce diabetes. Blood samples were examined through calorimetry to assess serum concentrations of glucose, blood urea nitrogen (BUN), and creatinine. To measure the microalbuminuria and transforming growth factor-ß (TGF-ß) levels and to evaluate the miRNAs expression levels of the kidney tissue, the ELISA method and the real-time PCR were used. The obtained results serve as in vivo evidence for the positive relationship between miR-192 and TGF-ß levels in the DN rats. A significant increase and decrease were found for miR-29a/b/c and the miR-192 expression of DN after treatment with S, C, and S+C. TGF-ß levels and microalbuminuria of diabetic rats also increased. The results obtained from this research study suggest that S, C, and S + C can improve DN by targeting miR-192 and miR-29 family and changing their expression. These findings suggest that miR-192 and miRs-29a/b/c can be potential targets for DN remediation.


Assuntos
Captopril/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/farmacologia , Espironolactona/farmacologia , Animais , Anti-Hipertensivos/farmacologia , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/induzido quimicamente , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Diuréticos/farmacologia , Combinação de Medicamentos , Reposicionamento de Medicamentos , Hiperglicemia/induzido quimicamente , Hiperglicemia/genética , Hiperglicemia/patologia , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Ratos , Ratos Wistar , Estreptozocina/administração & dosagem , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Resultado do Tratamento
8.
Food Chem ; 298: 125098, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31276942

RESUMO

This work aimed to optimize an aqueous extract rich in phenolic compounds and potential functional properties made of Ilex paraguariensis, Melissa officinalis, and Cymbopogon citratus. The lyophilized extract was used for the development of an ice cream. Total phenolics, FRAP, DPPH, Folin-Ciocalteu's reducing capacity, and total reducing capacity of different combinations of herbal extracts were tested and modeled using response surface methodology. Simultaneous optimisation was employed to maximize the bioactive compounds in the extract and the lyophilized optimum combination was added to ice cream. The lyophilized extract contained quercetin-3-rutinoside, hesperidin, isoquercetin, caffeic acid, and 5,7-dihydroxyflavone. The optimised extract, which showed antihypertensive, antidiabetic, and antioxidant activity using in vitro protocols, increased total phenolics and antioxidant activity in comparison to the control ice cream. The ice cream presented a sensory acceptance index of 83%. After 72 days of storage (-18 °C), total phenolics and antioxidant activity significantly decreased.


Assuntos
Indústria de Processamento de Alimentos/métodos , Sorvetes , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Adolescente , Adulto , Anti-Infecciosos/farmacologia , Anti-Hipertensivos/química , Anti-Hipertensivos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular , Cymbopogon/química , Feminino , Flavonoides/análise , Flavonoides/química , Armazenamento de Alimentos , Humanos , Sorvetes/análise , Ilex paraguariensis/química , Masculino , Melissa/química , Pessoa de Meia-Idade , Oligossacarídeos/química , Fenóis/química , Paladar
9.
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
10.
Anticancer Res ; 39(7): 3543-3551, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262878

RESUMO

BACKGROUND/AIM: Both bevacizumab (BEV) and soluble fms-like tyrosine kinase-1 (sFlt-1) have demonstrated anti-angiogenic effects, thereby causing hypertension and proteinuria. We hypothesized that anti-preeclamptic drugs that combat the action of sFlt-1 may reduce BEV's anti-tumor efficacy. MATERIALS AND METHODS: 3D co-cultured human mini-tumors consisting of endothelial cells, fibroblasts, and cancer cells were developed. The influence of anti-preeclamptic drugs and BEV on the invasion of mini-tumors embedded in collagen gel was evaluated. RESULTS: Mini-tumor spheroids that contained MDA-MB-231 cells showed higher invasion ability than spheroids with A549. Among the six anti-preeclamptic drugs investigated, only nicorandil enhanced the invasion of mini-tumors and inhibited the action of BEV. Glibenclamide, an ATP-sensitive potassium channel inhibitor, completely quenched the action of nicorandil on mini-tumors. CONCLUSION: In the human mini-tumor model, nicorandil aggravated the invasion of mini-tumors. These data raise the possibility that concomitant use of nicorandil counteracts the efficacy of BEV therapy.


Assuntos
Inibidores da Angiogênese/farmacologia , Anti-Hipertensivos/farmacologia , Bevacizumab/farmacologia , Esferoides Celulares/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Técnicas de Cocultura , Feminino , Fibroblastos/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Nicorandil/farmacologia , Pré-Eclâmpsia , Gravidez , Esferoides Celulares/fisiologia , Fator A de Crescimento do Endotélio Vascular/farmacologia
11.
Gen Physiol Biophys ; 38(3): 265-270, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31184313

RESUMO

This study investigated the effect of lisinopril (angiotensin-converting enzyme inhibitor) on potential behavioural alterations in spontaneously hypertensive rats (SHR). Three groups of 15-17-week-old rats were investigated for 2 weeks: Wistar control group, SHR group and SHR+lisinopril group. Systolic blood pressure (SBP) was normal in Wistar rats, SHR expressed hypertension and lisinopril normalized the SBP. We observed increased time spent in and increased frequency of entries to the central area of the open field in SHR, while lisinopril induced a trend to reduce the time spent in the central area of the open field and reduced the frequency of entries there. There was a positive correlation between SBP and reduced anxiety-like behaviour in normotensive rats; no correlations in the SHR or SHR+lisinopril groups were observed. We conclude that lisinopril normalized the increase in SBP and partly reversed the alterations of anxiety-like behaviour in SHR.


Assuntos
Anti-Hipertensivos/farmacologia , Ansiedade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipertensão/psicologia , Lisinopril/farmacologia , Animais , Ansiedade/prevenção & controle , Pressão Sanguínea , Hipertensão/fisiopatologia , Ratos , Ratos Endogâmicos SHR , Ratos Wistar
12.
Mol Med Rep ; 19(6): 4553-4560, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059021

RESUMO

Cardiac fibrosis secondary to long­term hypertension is known to promote cardiac dysfunction; however, few therapeutic agents are available for the treatment of this condition in clinical practice. The heptapeptide alamandine (Ala) has recently been identified as a component of the renin­angiotensin system (RAS), which exerts a protective effect against cardiac hypertrophy; however, it is unknown whether Ala may also be useful for the treatment of cardiac fibrosis. In the present study, the potential therapeutic effects of Ala on long­term hypertension­induced cardiac fibrosis were investigated in an aged, spontaneous hypertensive rat model. Weekly blood pressure (BP) measurements revealed that daily Ala treatment significantly decreased the systolic, diastolic and mean arterial BP compared with the control. Of note, the observed reduction in BP in Ala­treated animals markedly differed to that observed in rats treated with hydralazine (Hyd). Echocardiography further demonstrated that Ala treatment decreased the ratio of left ventricle mass to body weight, and alleviated structural and functional parameters associated with cardiac fibrosis, including left ventricular volume, ejection fraction and fractional shortening compared with the control and Hyd­treated groups. Furthermore, Ala deceased the density of cardiac fibrosis, as assessed by Masson and Sirius red staining; reduced expression of fibrotic proteins, including connective tissue growth factor, collagen I (COL1A1) and matrix metalloproteinase 9, was also observed. In addition, Ala treatment further decreased the expression of angiotensin II­induced fibrotic markers at the mRNA and protein levels in cultured cardiac fibroblasts; Ala­mediated inhibition of COL1A1 expression and Akt phosphorylation was inhibited via the Mas­related G protein receptor antagonist, PD123319. Collectively, the findings of the present study suggest that Ala is an effective anti­hypertensive peptide that can attenuate cardiac dysfunction and fibrosis induced by chronic hypertension, independent of BP.


Assuntos
Cardiomegalia/tratamento farmacológico , Fibrose/tratamento farmacológico , Hipertensão/tratamento farmacológico , Oligopeptídeos/farmacologia , Angiotensina II/genética , Angiotensina II/metabolismo , Animais , Anti-Hipertensivos/farmacologia , Pressão Sanguínea , Cardiomegalia/etiologia , Colágeno Tipo I/antagonistas & inibidores , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Fibrose/etiologia , Ventrículos do Coração/metabolismo , Hipertensão/complicações , Imidazóis/farmacologia , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piridinas/farmacologia , Ratos , Ratos Endogâmicos SHR , Sistema Renina-Angiotensina
13.
Int J Mol Sci ; 20(9)2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31052341

RESUMO

Resveratrol increases the production of nitric oxide (NO) in endothelial cells by upregulating the expression of endothelial NO synthase (eNOS), stimulating eNOS enzymatic activity, and preventing eNOS uncoupling. At the same time, resveratrol inhibits the synthesis of endothelin-1 and reduces oxidative stress in both endothelial cells and smooth muscle cells. Pathological stimuli-induced smooth muscle cell proliferation, vascular remodeling, and arterial stiffness can be ameliorated by resveratrol as well. In addition, resveratrol also modulates immune cell function, inhibition of immune cell infiltration into the vascular wall, and improves the function of perivascular adipose tissue. All these mechanisms contribute to the protective effects of resveratrol on vascular function and blood pressure in vivo. Sirtuin 1, AMP-activated protein kinase, and estrogen receptors represent the major molecules mediating the vascular effects of resveratrol.


Assuntos
Anti-Hipertensivos/farmacologia , Antioxidantes/farmacologia , Endotélio Vascular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Resveratrol/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Humanos
14.
Mar Drugs ; 17(5)2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31086041

RESUMO

The peptide QAGLSPVR, which features high angiotensin-I-converting enzyme (ACE) inhibitory activity, was identified in our previous study. In this study, the in vivo antihypertensive effect of QAGLSPVR was evaluated. Results showed that QAGLSPVR exerts a clear antihypertensive effect on spontaneously hypertensive rats (SHRs), and the systolic and diastolic blood pressures of the rats remarkably decreased by 41.86 and 40.40 mm Hg, respectively, 3 h after peptide administration. The serum ACE activities of SHRs were determined at different times, and QAGLSPVR was found to decrease ACE activities in serum; specifically, minimal ACE activity was found 3 h after administration. QAGLSPVR could be completely absorbed by the Caco-2 cell monolayer, and its transport percentage was 3.5% after 2 h. The transport route results of QAGLSPVR showed that Gly-Sar and wortmannin exert minimal effects on the transport percentage of the peptide (p> 0.05), thus indicating that QAGLSPVR transport through the Caco-2 cell monolayer is not mediated by peptide transporter 1 or transcytosis. By contrast, cytochalasin D significantly increased QAGLSPVR transport (p< 0.05); thus, QAGLSPVR may be transported through the Caco-2 cell monolayer via the paracellular pathway.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Oligopeptídeos/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacocinética , Animais , Anti-Hipertensivos/farmacocinética , Células CACO-2 , Captopril/farmacologia , Humanos , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Masculino , Oligopeptídeos/farmacocinética , Peptidil Dipeptidase A/sangue , Ratos Endogâmicos SHR
15.
Mayo Clin Proc ; 94(5): 776-782, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31054605

RESUMO

OBJECTIVE: To evaluate the prevalence of apparent treatment-resistant hypertension (aTR-hypertension) in US adults with treated hypertension by using the nationally representative National Health and Nutrition Examination Survey (NHANES). PATIENTS AND METHODS: Nonpregnant US adults older than 20 years with a self-reported history of treated hypertension who had blood pressure measured in NHANES cycles 2007 to 2014 were included in this study. Study participants were stratified into 4 groups according to average blood pressure and antihypertensive medication use: well-controlled hypertension, undertreated hypertension, aTR-hypertension by the 2017 guideline, and aTR-hypertension by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guideline. National Health and Nutrition Examination Survey sample weights were used to estimate the national prevalence. RESULTS: From 2007 to 2014, 5512 participants with treated hypertension representing 46.7 million people nationally were included. Compared with JNC 7 guideline criteria, application of the 2017 high blood pressure guideline criteria increased the prevalence of aTR-hypertension in US adults with treated hypertension from 12.0% to 15.95%, identifying an additional 1.85 million individuals with aTR-hypertension nationally. Individuals newly reclassified as having aTR-hypertension were younger. However, the prevalence of thiazide diuretic use remained less than 70%, and that of mineralocorticoid antagonist use remained less than 10% regardless of the guideline definition. CONCLUSION: On the basis of the 2017 high blood pressure guideline, the prevalence of aTR-hypertension is 15.95% in US adults with treated hypertension. This represents an absolute increase of 4% (1.85 million additional individuals nationally) compared with the JNC 7 guideline definition, with a consistent increase across all subpopulations with treated hypertension.


Assuntos
Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/epidemiologia , Idoso , Anti-Hipertensivos/uso terapêutico , Determinação da Pressão Arterial , Estudos Transversais , Feminino , Humanos , Hipertensão/classificação , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Guias de Prática Clínica como Assunto , Prevalência , Índice de Gravidade de Doença , Estados Unidos/epidemiologia
16.
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
17.
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
18.
Molecules ; 24(7)2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30934724

RESUMO

A single herb can contain multiple constituents with diverse bioactivities. We found that the extract of Citrus unshiu peel (CUP), induced abnormal vasoconstriction responses on the freshly isolated rat aortic rings in vitro. CUP stimulated the vasoconstriction alone, and it suppressed the phenylephrine-stimulated vasoconstriction. We studied the reasons behind this abnormal vasoconstriction pattern. Major constituents of CUP were determined and evaluated for their vaso-activities. Notably, synephrine, a contractile agonist, and nobiletin, newly identified to have anti-contractile activity co-existed in CUP. Synephrine and nobiletin competitively blocked or activated the same contractile targets resulting in contradicting and abnormal vasoconstriction responses. Accordingly, the vasoconstriction pattern varies significantly depending on the relative contents of synephrine and nobiletin in CUP. Interestingly, this response pattern could be observed with another plant extract, Acorus gramineus Sol. Collectively, we demonstrated that active ingredients with contradicting bioactivities could co-exist in a single plant extract, interact and produce abnormal response patterns in bioassay, which would give an important insight into the interpretation of unusual activity patterns induced by plant extracts.


Assuntos
Anti-Hipertensivos/farmacologia , Citrus/química , Flavonas/farmacologia , Extratos Vegetais/farmacologia , Sinefrina/farmacologia , Vasoconstritores/farmacologia , Anti-Hipertensivos/química , Flavonas/química , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Sinefrina/química , Vasoconstritores/química
19.
Mar Drugs ; 17(4)2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30934709

RESUMO

In this study, the antihypertensive activity of Purafect®-smooth hound viscera protein hydrolysate (VPH) and its peptide fraction with molecular weight (MW) below 1 kDa (VPH-I) was investigated. In addition, the lipase inhibitory activity, as well the anticoagulant potential, in vitro, were assessed. The antihypertensive effects of VPH and VPH-I were studied during 24 h (short-term effect) and 30 days (long-term effect) using high-salt (18% NaCl) and -fructose (10%) diet (HSFD)-induced hypertension. Data showed that, 4 h post-administration of VPH and VPH-I (200 mg/kg BW), the systolic blood pressure of rats was reduced by about 6 and 9 mmHg, respectively. These effects were similar to that obtained with Captopril (~9 mmHg at t = 4 h). On the other hand, exposing the rats to daily to HSFD, coupled to the administration of viscera peptides, was found to attenuate hypertension. In addition, the proteins' treatments were able to correct lipid and glycemic disorders, by reducing the total cholesterol and triglyceride contents and resorting to the plasma glucose level, compared to the HSFD group. Overall, the present findings demonstrated the preventive effect of VPH-peptides from hypertension complications, as a result of their biological properties.


Assuntos
Anti-Hipertensivos/farmacologia , Colesterol/metabolismo , Hipertensão/tratamento farmacológico , Hipertensão/prevenção & controle , Hidrolisados de Proteína/farmacologia , Animais , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Dieta , Frutose/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Cloreto de Sódio/administração & dosagem
20.
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
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