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1.
Int J Nanomedicine ; 16: 1377-1390, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33658778

RESUMO

Background: Vascular drug delivery becomes a promising direction in the development of novel therapeutic strategies in the treatment of cardiovascular pathologies, such as hypertension. However, targeted delivery of hydrophobic substances, with poor bioavailability, remains a challenge. Here, we described the hypotensive effects of a low dose of curcumin delivered to the vascular wall using hyaluronic acid-based nanocapsules. Methods: The group of hypertensive TGR(m-Ren2)27 rats, was administrated respectively with the vehicle, curcumin solution or curcumin delivered using hyaluronic acid-based nanocapsules (HyC12-Cur), for 7 days each, maintaining the wash-out period between treatments. Arterial blood pressure (systolic - SBP, diastolic - DBP) and heart rate (HR) were monitored continuously using a telemetry system (Data Science International), and Mean Arterial Pressure (MAP) was calculated from SBP and DBP. Results: In hypertensive rats, a low dose of curcumin (4.5 mg/kg) administrated in HyC12-Cur for 7 days resulted in a gradual inhibition of SBP, DBP and MAP increase without an effect on HR. At the end of HyC12-Cur - based treatment changes in SBP, DBP and MAP amounted to -2.0±0.8 mmHg, -3.9±0.7 mmHg and -3.3±0.7 mmHg, respectively. In contrast, the administration of a curcumin solution (4.5 mg/kg) did not result in a significant hypotensive effect and the animals constantly developed hypertension. Vascular delivery of capsules with curcumin was confirmed using newly developed fluorine-rich nanocapsules (HyFC10-PFOB) with a shell based on a HA derivative and similar size as HyC12-Cur. HyFC10-PFOB gave fluorine signals in rat aortas analyzed ex vivo with a 19F NMR technique after a single intragastric administration. Conclusion: These results suggest that nanocapsules based on hyaluronic acid, the ubiquitous glycosaminoglycan of the extracellular matrix and an integral part of endothelial glycocalyx, may represent a suitable approach to deliver hydrophobic, poorly bioavailable compounds, to the vascular wall.


Assuntos
Curcumina/administração & dosagem , Curcumina/uso terapêutico , Ácido Hialurônico/química , Hipertensão/tratamento farmacológico , Nanocápsulas/química , Administração Oral , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Pressão Sanguínea/efeitos dos fármacos , Curcumina/farmacologia , Diástole/efeitos dos fármacos , Relação Dose-Resposta a Droga , Flúor/química , Frequência Cardíaca/efeitos dos fármacos , Hidrodinâmica , Interações Hidrofóbicas e Hidrofílicas , Hipertensão/fisiopatologia , Espectroscopia de Ressonância Magnética , Masculino , Tamanho da Partícula , Ratos , Eletricidade Estática , Sístole/efeitos dos fármacos
2.
Medicine (Baltimore) ; 99(43): e22288, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120732

RESUMO

INTRODUCTION: Dexmedetomidine and midazolam have become important approaches for the sedation of dental surgery. However, the comparison of these 2 drugs for the sedation of dental surgery has not been well established. We conduct a systematic review and meta-analysis to evaluate the efficacy of dexmedetomidine versus midazolam for dental surgery. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials are searched. Randomized controlled trials (RCTs) assessing the influence of dexmedetomidine versus midazolam on dental surgery are included. Two investigators independently have searched articles, extracted data, and assessed the quality of included studies. Meta-analysis is performed using the random-effect model. RESULTS: Five RCTs and 420 patients are included in the meta-analysis. Compared with midazolam intervention for dental surgery, dexmedetomidine intervention has similar lowest SpO2, lowest heart rate and lowest systolic blood pressure, duration of surgery, and total volume of local anesthetic, but is associated with stable and reduced lowest diastolic blood pressure. CONCLUSIONS: Similar benefits of dexmedetomidine and midazolam intervention are observed for the sedation of dental surgery in terms of SpO2, heart rate, systolic blood pressure, and the volume of local anesthetic, but dexmedetomidine may result in more stable diastolic blood pressure.


Assuntos
Dexmedetomidina/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Midazolam/uso terapêutico , Procedimentos Cirúrgicos Bucais , Anestésicos Locais/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Diástole/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Duração da Cirurgia , Oxigênio/sangue , Sístole/efeitos dos fármacos
3.
PLoS One ; 15(7): e0236680, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32722688

RESUMO

Cachexia is a common multifactorial syndrome in the advanced stages of cancer and accounts for approximately 20-30% of all cancer-related fatalities. In addition to the progressive loss of skeletal muscle mass, cancer results in impairments in cardiac function. We recently demonstrated that WFA attenuates the cachectic skeletal muscle phenotype induced by ovarian cancer. The purpose of this study was to investigate whether ovarian cancer induces cardiac cachexia, the possible pathway involved, and whether WFA attenuates cardiac cachexia. Xenografting of ovarian cancer induced cardiac cachexia, leading to the loss of normal heart functions. Treatment with WFA rescued the heart weight. Further, ovarian cancer induced systolic dysfunction and diastolic dysfunction Treatment with WFA preserved systolic function in tumor-bearing mice, but diastolic dysfunction was partially improved. In addition, WFA abrogated the ovarian cancer-induced reduction in cardiomyocyte cross-sectional area. Finally, treatment with WFA ameliorated fibrotic deposition in the hearts of tumor-bearing animals. We observed a tumor-induced MHC isoform switching from the adult MHCα to the embryonic MHCß isoform, which was prevented by WFA treatment. Circulating Ang II level was increased significantly in the tumor-bearing, which was lowered by WFA treatment. Our results clearly demonstrated the induction of cardiac cachexia in response to ovarian tumors in female NSG mice. Further, we observed induction of proinflammatory markers through the AT1R pathway, which was ameliorated by WFA, in addition to amelioration of the cachectic phenotype, suggesting WFA as a potential therapeutic agent for cardiac cachexia in oncological paradigms.


Assuntos
Caquexia/tratamento farmacológico , Caquexia/etiologia , Coração/efeitos dos fármacos , Miocárdio/patologia , Neoplasias Ovarianas/complicações , Vitanolídeos/farmacologia , Animais , Caquexia/patologia , Caquexia/fisiopatologia , Linhagem Celular Tumoral , Transformação Celular Neoplásica , Diástole/efeitos dos fármacos , Diástole/fisiologia , Feminino , Coração/fisiopatologia , Camundongos , Fenótipo , Sístole/efeitos dos fármacos , Sístole/fisiologia , Vitanolídeos/uso terapêutico
4.
Clin Sci (Lond) ; 134(11): 1191-1218, 2020 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-32432676

RESUMO

Myocardial infarction (MI) is the leading cause of mortality worldwide. Interleukin (IL)-33 (IL-33) is a cytokine present in most cardiac cells and is secreted on necrosis where it acts as a functional ligand for the ST2 receptor. Although IL-33/ST2 axis is protective against various forms of cardiovascular diseases, some studies suggest potential detrimental roles for IL-33 signaling. The aim of the present study was to examine the effect of IL-33 administration on cardiac function post-MI in mice. MI was induced by coronary artery ligation. Mice were treated with IL-33 (1 µg/day) or vehicle for 4 and 7 days. Functional and molecular changes of the left ventricle (LV) were assessed. Single cell suspensions were obtained from bone marrow, heart, spleen, and peripheral blood to assess the immune cells using flow cytometry at 1, 3, and 7 days post-MI in IL-33 or vehicle-treated animals. The results of the present study suggest that IL-33 is effective in activating a type 2 cytokine milieu in the damaged heart, consistent with reduced early inflammatory and pro-fibrotic response. However, IL-33 administration was associated with worsened cardiac function and adverse cardiac remodeling in the MI mouse model. IL-33 administration increased infarct size, LV hypertrophy, cardiomyocyte death, and overall mortality rate due to cardiac rupture. Moreover, IL-33-treated MI mice displayed a significant myocardial eosinophil infiltration at 7 days post-MI when compared with vehicle-treated MI mice. The present study reveals that although IL-33 administration is associated with a reparative phenotype following MI, it worsens cardiac remodeling and promotes heart failure.


Assuntos
Eosinófilos/metabolismo , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Interleucina-33/farmacologia , Infarto do Miocárdio/fisiopatologia , Sístole/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Citocinas/sangue , Fragmentação do DNA/efeitos dos fármacos , Diástole/efeitos dos fármacos , Eosinofilia/patologia , Eosinófilos/efeitos dos fármacos , Fibrose , Ventrículos do Coração/efeitos dos fármacos , Hipertrofia Ventricular Esquerda/patologia , Mediadores da Inflamação/sangue , Interleucina-33/administração & dosagem , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Esplenomegalia/patologia , Regulação para Cima/efeitos dos fármacos , Remodelação Ventricular/genética , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
5.
Metabolism ; 109: 154223, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32275972

RESUMO

OBJECTIVE: Obesity is associated with myocardial fibrosis and impaired diastolic relaxation, abnormalities that are especially prevalent in women. Normal coronary vascular endothelial function is integral in mediating diastolic relaxation, and recent work suggests increased activation of the endothelial cell (EC) mineralocorticoid receptor (ECMR) is associated with impaired diastolic relaxation. As the endothelial Na+ channel (EnNaC) is a downstream target of the ECMR, we sought to determine whether EC-specific deletion of the critical alpha subunit, αEnNaC, would prevent diet induced-impairment of diastolic relaxation in female mice. METHODS AND MATERIALS: Female αEnNaC KO mice and littermate controls were fed a Western diet (WD) high in fat (46%), fructose corn syrup (17.5%) and sucrose (17.5%) for 12-16 weeks. Measurements were conducted for in vivo cardiac function, in vitro cardiomyocyte stiffness and EnNaC activity in primary cultured ECs. Additional biochemical studies examined indicators of oxidative stress, including aspects of antioxidant Nrf2 signaling, in cardiac tissue. RESULTS: Deletion of αEnNaC in female mice fed a WD significantly attenuated WD mediated impairment in diastolic relaxation. Improved cardiac relaxation was accompanied by decreased EnNaC-mediated Na+ currents in ECs and reduced myocardial oxidative stress. Further, deletion of αEnNaC prevented WD-mediated increases in isolated cardiomyocyte stiffness. CONCLUSION: Collectively, these findings support the notion that WD feeding in female mice promotes activation of EnNaC in the vasculature leading to increased cardiomyocyte stiffness and diastolic dysfunction.


Assuntos
Diástole/efeitos dos fármacos , Dieta Ocidental/efeitos adversos , Células Endoteliais/química , Coração/fisiopatologia , Canais de Sódio/metabolismo , Rigidez Vascular/efeitos dos fármacos , Animais , Células Cultivadas , Células Endoteliais/metabolismo , Feminino , Camundongos , Camundongos Knockout , Miócitos Cardíacos/patologia , Estresse Oxidativo , Canais de Sódio/deficiência
6.
J Vis Exp ; (156)2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32090990

RESUMO

Zebrafish are increasingly utilized as a model organism for cardiomyopathies and regeneration. Current methods evaluating cardiac function fail to reliably detect segmental mechanics and are not readily feasible in zebrafish. Here we present a semiautomated, open-source method for the quantitative assessment of four-dimensional (4D) segmental cardiac function: displacement analysis of myocardial mechanical deformation (DIAMOND). Transgenic embryonic zebrafish were imaged in vivo using a light-sheet fluorescence microscopy system with 4D cardiac motion synchronization. Acquired 3D digital hearts were reconstructed at end-systole and end-diastole, and the ventricle was manually segmented into binary datasets. Then, the heart was reoriented and isotropically resampled along the true short axis, and the ventricle was evenly divided into eight portions (I-VIII) along the short axis. Due to the different resampling planes and matrices at end-systole and end-diastole, a transformation matrix was applied for image registration to restore the original spatial relationship between the resampled systolic and diastolic image matrices. After image registration, the displacement vector of each segment from end-systole to end-diastole was calculated based on the displacement of mass centroids in three dimensions (3D). DIAMOND shows that basal myocardial segments adjacent to the atrioventricular canal undergo the highest mechanical deformation and are the most susceptible to doxorubicin-induced cardiac injury. Overall, DIAMOND provides novel insights into segmental cardiac mechanics in zebrafish embryos beyond traditional ejection fraction (EF) under both physiological and pathological conditions.


Assuntos
Algoritmos , Embrião não Mamífero/fisiologia , Coração/embriologia , Coração/fisiologia , Processamento de Imagem Assistida por Computador , Peixe-Zebra/embriologia , Animais , Animais Geneticamente Modificados , Diástole/efeitos dos fármacos , Diástole/fisiologia , Doxorrubicina/farmacologia , Embrião não Mamífero/efeitos dos fármacos , Coração/efeitos dos fármacos , Testes de Função Cardíaca , Ventrículos do Coração/efeitos dos fármacos , Imageamento Tridimensional , Receptores Notch/metabolismo , Sístole/fisiologia
7.
J Physiol Sci ; 70(1): 2, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32039689

RESUMO

Fragrance inhalation of essential oils is widely used in aromatherapy, and it is known to affect blood pressure (BP) and heart rate (HR) via autonomic control of circulation. In this study, we aimed to test the hypothesis that the changes in hemodynamics with fragrance inhalation were observed along with changes in muscle sympathetic nerve activity (MSNA). In study 1, thirteen healthy men were exposed to fragrance stimulation of grapefruit essential oil for 10 min, and BP, HR, and MSNA were continuously measured. In study 2, another nine healthy men were exposed to the same fragrance stimulation; responses in BP and HR were continuously measured, and plasma noradrenaline and cortisol concentrations were determined. We found that diastolic BP increased significantly during fragrance inhalation, while the other variables remained unchanged in both studies. Although MSNA burst frequency, burst incidence, and total activity remained unchanged during fragrance inhalation, we found a significant linear correlation between changes in diastolic BP in the last 5 min of fragrance inhalation and changes in MSNA burst frequency. The plasma cortisol concentration decreased significantly at 10 min of fragrance inhalation, though the noradrenaline concentration remained unchanged. These results suggest, for the first time, that changes in BP with fragrance inhalation of essential oil are associated with changes in MSNA even with decreased stress hormone.


Assuntos
Citrus paradisi/química , Diástole/efeitos dos fármacos , Músculo Esquelético/inervação , Óleos Voláteis/farmacologia , Óleos Vegetais/farmacologia , Sistema Nervoso Simpático/efeitos dos fármacos , Estudos Cross-Over , Humanos , Masculino , Odorantes , Óleos Voláteis/química , Óleos Vegetais/química , Sistema Nervoso Simpático/fisiologia , Adulto Jovem
8.
PLoS One ; 15(2): e0228650, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32053644

RESUMO

BACKGROUND: Globally, the burden of stroke is increasing at an alarming rate. Factors associated with stroke among hypertensive patients are not consistent across different studies and there are limited studies particularly to hypertensive stroke in the particular setting. This study aimed to assess factors associated with stroke among patients with hypertension in Ayder Comprehensive Specialized Hospital, Mekelle, Tigray, Ethiopia, in 2018. METHODS: Hospital-based case-control study was conducted from February to April 2018. Cases were adult hypertensive patients with stroke and controls were adult hypertensive patients without a stroke. Cases and controls were identified from the patient's card review. Using a systematic random sampling technique 89 cases and 356 controls were included in this study. Record review, physical measurement, and interview techniques were used to collect data. Data was entered and analyzed by using SPSS version 23. Variables with a p-value of less than 0.25 in the bivariate logistic regression were selected for multivariable logistic regression. The adjusted odds ratio and 95% confidence interval were used to determine the association. P-value <0.05 was used to declare statistical significance. RESULTS: The mean age of cases and controls were 56.3 years (SD±13.53) and 51.9 years (SD±12.67) respectively. Lost to follow-up (AOR = 2.474, 95%CI: 1.368-4.929), alcohol drinking (AOR = 2.440, 95%CI: 1.291-4.613), use of excessive salt in diet (AOR = 3.249, 95%CI: (1.544-6.837), medication non-adherence (AOR = 3.967, 95%CI: 2.256-6.973), uncontrolled systolic blood pressure, (AOR = 3.196, 95%CI: 1.60-6.382), uncontrolled diastolic blood pressure (AOR = 2.204, 95%CI: 1.130-4.297) and high cholesterol level (AOR = 2.413, 95%CI: 1.319-4.414) were found to be significant factors. CONCLUSION: Lost to follow-up, alcohol drinking, uses of excessive salt in diet, medication non-adherence, and uncontrolled systolic and diastolic blood pressure were associated with stroke. Health education on lifestyle practices and hypertension-related complications in each follow-up visit is very essential for improving the primary stroke prevention.


Assuntos
Hipertensão/complicações , Hipertensão/epidemiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Consumo de Bebidas Alcoólicas , Alcoolismo/complicações , Antropometria , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Estudos de Casos e Controles , Estudos Transversais , Diástole/efeitos dos fármacos , Etiópia/epidemiologia , Exercício Físico , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Hospitais , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Análise de Regressão , Fatores de Risco , Cloreto de Sódio na Dieta , Acidente Vascular Cerebral/prevenção & controle , Sístole , Resultado do Tratamento
9.
Aging Cell ; 19(2): e13086, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31823466

RESUMO

Even in healthy aging, cardiac morbidity and mortality increase with age in both mice and humans. These effects include a decline in diastolic function, left ventricular hypertrophy, metabolic substrate shifts, and alterations in the cardiac proteome. Previous work from our laboratory indicated that short-term (10-week) treatment with rapamycin, an mTORC1 inhibitor, improved measures of these age-related changes. In this report, we demonstrate that the rapamycin-dependent improvement of diastolic function is highly persistent, while decreases in both cardiac hypertrophy and passive stiffness are substantially persistent 8 weeks after cessation of an 8-week treatment of rapamycin in both male and female 22- to 24-month-old C57BL/6NIA mice. The proteomic and metabolomic abundance changes that occur after 8 weeks of rapamycin treatment have varying persistence after 8 further weeks without the drug. However, rapamycin did lead to a persistent increase in abundance of electron transport chain (ETC) complex components, most of which belonged to Complex I. Although ETC protein abundance and Complex I activity were each differentially affected in males and females, the ratio of Complex I activity to Complex I protein abundance was equally and persistently reduced after rapamycin treatment in both sexes. Thus, rapamycin treatment in the aged mice persistently improved diastolic function and myocardial stiffness, persistently altered the cardiac proteome in the absence of persistent metabolic changes, and led to persistent alterations in mitochondrial respiratory chain activity. These observations suggest that an optimal translational regimen for rapamycin therapy that promotes enhancement of healthspan may involve intermittent short-term treatments.


Assuntos
Cardiomegalia/tratamento farmacológico , Complexo I de Transporte de Elétrons/metabolismo , Ventrículos do Coração/efeitos dos fármacos , Miocárdio/metabolismo , Proteoma/efeitos dos fármacos , Sirolimo/farmacologia , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Animais , Cardiomegalia/metabolismo , Cardiomegalia/fisiopatologia , Diástole/efeitos dos fármacos , Feminino , Identidade de Gênero , Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteoma/metabolismo , Espectrometria de Massas em Tandem
11.
J Clin Hypertens (Greenwich) ; 21(12): 1823-1830, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31769172

RESUMO

Elevated morning blood pressure (BP) has a significantly increased risk of cardiovascular events, so morning BP is of substantial clinical importance for the management of hypertension. This study aimed to evaluate early morning BP control and its determines among treated patients with controlled office BP. From May to October 2018, 600 treated patients with office BP < 140/90 mm Hg were recruited from hypertension clinics. Morning BP was measured at home for 7 days. Morning home systolic blood pressure (SBP) increased by an average of 11.5 mm Hg and that morning home diastolic blood pressure (DBP) increased by an average of 5.6 mm Hg compared with office BP. Morning home SBP, DBP, and their moving average were more likely to be lower among patients with a office SBP < 120 mm Hg than among patients with a office SBP ranging from 120 to 129 mm Hg and from 130 to 139 mm Hg (P < .001). A total of 45% of patients had early morning BP < 135/85 mm Hg. The following factors were significantly correlated with morning BP control: male sex, age of <65 years, absence of habitual snoring, no drinking, adequate physical activity, no habit of high salt intake, office BP < 120/80 mm Hg, and combination of a calcium channel blocker (CCB) and angiotensin receptor blocker or angiotensin-converting enzyme inhibitor (ARB/ACEI). Less than half of patients with controlled office BP had controlled morning BP and that positive changes may be related to an office BP < 120/80 mm Hg, combination of a CCB and ACEI/ARB and a series of lifestyle adjustments.


Assuntos
Anti-Hipertensivos/uso terapêutico , Determinação da Pressão Arterial/tendências , Pressão Sanguínea/fisiologia , Hipertensão/tratamento farmacológico , Adulto , Idoso , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Determinação da Pressão Arterial/métodos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Ritmo Circadiano , Estudos Transversais , Diástole/efeitos dos fármacos , Quimioterapia Combinada , Comportamento Alimentar/psicologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Comportamento de Redução do Risco , Cloreto de Sódio na Dieta/urina , Sístole/efeitos dos fármacos
12.
J Clin Hypertens (Greenwich) ; 21(12): 1831-1840, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31769184

RESUMO

Mozambique has low levels of detection, treatment, and control of hypertension. However, data on target organ damage and clinical outcomes are lacking. The authors aimed at characterizing the clinical profile, pattern of target organ damage, and short-term outcomes of patients referred to a first referral urban hospital in a low-income setting in Africa. We conducted a prospective descriptive cohort study from February 2016 to May 2017 in Maputo, Mozambique. Adult patients with systolic and diastolic blood pressure ≥180 mm Hg and/or ≥110 mm Hg, respectively, or any systolic blood pressure above 140 mm Hg and/or diastolic blood pressure above 90 mm Hg in the presence of target organ damage (with or without antihypertensive treatment) were submitted to detailed physical examination, funduscopy, laboratory profile, electrocardiography, and echocardiography. Six months after the occurrence of complications (stroke, heart failure, and renal failure), hospital admission and death were assessed. Overall, 116 hypertensive patients were recruited (mean age 57.5 ± 12.8 years old; 111[95.7%] black; 81[70%] female) of which 79 had severe hypertension. The baseline mean values recorded for systolic and diastolic blood pressure were 192.3 ± 23.6 and 104.2 ± 15.2 mm Hg, respectively. Most patients (93; 80.2%) were on antihypertensive treatment. Patients' risk profile revealed dyslipidemia, obesity, and diabetes in 59(54.1%), 48(42.5%), and 23(19.8%), respectively. Target organ damage was found in 111 patients. The commonest being left atrial enlargement 91(84.5%), left ventricular hypertrophy 57(50.4%), hypertensive retinopathy 30(26.3%), and chronic kidney disease 27(23.3%). Major events during 6-month follow-up were hospitalizations in 10.3% and death in 8.6% of the patients. Worsening of target organ damage occurred in 10 patients: four stroke, two heart failure, and four renal damage. Patients with severe hypertension and target organ damage were young with high-risk profile, low hypertension control, and high occurrence of complications during short-term follow-up. Efforts to improve high blood pressure control are needed to reduce premature mortality in this highly endemic poor setting.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Recursos em Saúde/provisão & distribução , Hospitais Urbanos/economia , Hipertensão/complicações , Adulto , Idoso , Anti-Hipertensivos/uso terapêutico , Diástole/efeitos dos fármacos , Feminino , Seguimentos , Recursos em Saúde/tendências , Insuficiência Cardíaca/epidemiologia , Hospitalização , Hospitais Urbanos/estatística & dados numéricos , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Retinopatia Hipertensiva/epidemiologia , Hipertrofia Ventricular Esquerda/epidemiologia , Masculino , Pessoa de Meia-Idade , Moçambique/epidemiologia , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Insuficiência Renal/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Sístole/efeitos dos fármacos
14.
Mol Nutr Food Res ; 63(24): e1900418, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31655498

RESUMO

SCOPE: Cardiac fibrosis is a key feature of cardiac remodeling. Recently, a protective role for resveratrol (RES) in pressure-overload-induced cardiac hypertrophy and contractile dysfunction has been demonstrated. However, the effect of RES on cardiac fibrosis and diastolic function in this model remains unclear. METHODS AND RESULTS: Cardiac remodeling is induced in mice by transverse aortic constriction (TAC) for 2-4 weeks. RES is administered at dose of 5 or 50 mg kg-1  d-1 for 2 weeks. It is found that RES administration at 50 mg kg-1  d-1 significantly attenuates TAC-induced adverse cardiac systolic and diastolic function, fibrosis, inflammation, and oxidative stress via inhibiting PTEN degradation and the downstream mediators. However, RES at 5 mg kg-1  d-1 has no significant effects. RES at 50 mg kg-1  d-1 also ameliorates pre-established adverse cardiac function and remodeling induced by TAC. Treatment with PTEN inhibitor VO-OHpic (10 mg kg-1  d-1 ) for 2 weeks abolishes RES-mediated protective effects. Additionally, the effect of RES (100 µm) on inhibition of Ang II-induced fibroblast proliferation and activation in vitro is verified. CONCLUSIONS: The findings provide new evidence that RES plays a critical role in the progression of cardiac fibrosis and diastolic dysfunction, and suggest that RES may be a promising therapeutic agent for cardiac fibrosis.


Assuntos
Cardiotônicos/farmacologia , Coração/efeitos dos fármacos , Miocárdio/patologia , Resveratrol/farmacologia , Animais , Diástole/efeitos dos fármacos , Fibrose , Coração/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Miocardite/tratamento farmacológico , Miocardite/etiologia , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo
15.
J Pharmacol Sci ; 141(1): 9-16, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31521490

RESUMO

The role of the Na+ current in the automaticity of the pulmonary vein myocardium was examined in isolated guinea pig pulmonary vein cardiomyocytes and tissue preparations. Tetrodotoxin inhibited the automaticity of pulmonary vein tissue preparations by suppressing the diastolic depolarization of the action potential. ATX-II, which increased the density of persistent component of the Na+ current (late INa), induced a depolarization of the resting membrane potential followed by spontaneous firing of action potentials. GS-458967, which inhibited the late INa, suppressed the diastolic depolarization and the firing of action potentials. Pilsicainide, which inhibited only the transient component of Na+ current (peak INa), had no effect on the firing frequency. GS-458967 had no effect on the contractile force of the working myocardium. In conclusion, late INa is involved in the diastolic depolarization and automaticity of the pulmonary vein myocardium. Late INa inhibitors appear to be effective therapeutic agents for atrial fibrillation with minimum adverse effects on the working myocardium.


Assuntos
Miócitos Cardíacos/metabolismo , Veias Pulmonares/citologia , Piridinas/farmacologia , Sódio/metabolismo , Triazóis/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Fibrilação Atrial/tratamento farmacológico , Células Cultivadas , Diástole/efeitos dos fármacos , Cobaias , Lidocaína/análogos & derivados , Lidocaína/farmacologia , Masculino , Potenciais da Membrana/efeitos dos fármacos , Veias Pulmonares/metabolismo , Piridinas/uso terapêutico , Tetrodotoxina/farmacologia , Triazóis/uso terapêutico
16.
Med Arch ; 73(3): 157-162, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31391706

RESUMO

Introduction: Hypertension is significantly contributing to global mortality and morbidity and has been identified as the most important modifiable risk factor for early development of cardiovascular diseases (CVD). Aim: The aim of this study was to investigate the efficacy of different combinations of antihypertensive therapy on blood pressure, arterial stiffness and peripheral resistance in patients with essential hypertension using the brachial oscillometric ambulatory blood pressure monitor. Methods: This study was designed as an observational, prospective, multi centric study conducted in eight primary care centers of the Health Center of Canton Sarajevo during the period of six months. The study included 655 participants, both genders, aged between 30 and 75, who were diagnosed with hypertension according to the ESC/ESH guidelines. Participants were divided into six treatment groups based on the hypertensive drug therapy they were using; lisinopril, losartan or valsartan alone or in combination with hydrochlorothiazide (A, B and C group respectively) or combination of lisinopril, losartan or valsartan with/without hydrochlorothiazide together with amlodipine (D, E and F respectively). The participants were monitored at baseline, after 3 and 6 months (1st and 2nd follow-up). Brachial oscillometric ambulatory blood pressure monitor was used for measuring systolic (SBP), diastolic (DBP), pulse pressure (PP), pulse wave velocity (PWV) and peripheral resistance (PR). Results: SBP, DPB, PP, and PWV significantly decreased from baseline to 2nd follow-up in all treatment groups. The mean reductions in SBP were from -11.7 (95%CI; 9.3- 14.1) to -23.2 (95%CI; 18.3-28.1) mmHg and DBP reductions varied from -5.5 (95%CI; 3.9- 7.1) to -13.4 (95%CI; 7.7-19.1) mmHg. PWV decreased in all treatment groups (from -3.3% to -8.2%). Treatment regiment was not associated with significant differences in SBP, DBP, PP or PWV reductions or their values measured at 2nd follow-up. Peripheral resistance significantly decreased only in group C (p=0.011), group D (p=0.009) and group F (p=0.027). Conclusion: These data suggest that lisinopril/lisinopril + hydrochlorothiazide, losartan/losartan + hydrochlorothiazide and valsartan/valsartan + hydrochlorothiazide alone or in combination with amlodipine are equally effective and well tolerated for the reduction of both systolic and diastolic blood pressure and improve arterial stiffness in patients with essential hypertension.


Assuntos
Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Resistência Vascular/efeitos dos fármacos , Rigidez Vascular/efeitos dos fármacos , Idoso , Anlodipino/farmacologia , Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Artérias , Diástole/efeitos dos fármacos , Combinação de Medicamentos , Hipertensão Essencial/tratamento farmacológico , Feminino , Humanos , Hidroclorotiazida/farmacologia , Hidroclorotiazida/uso terapêutico , Lisinopril/farmacologia , Lisinopril/uso terapêutico , Losartan/farmacologia , Losartan/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Onda de Pulso , Sístole/efeitos dos fármacos , Valsartana/farmacologia , Valsartana/uso terapêutico
17.
ESC Heart Fail ; 6(5): 927-935, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31400090

RESUMO

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a unique class of oral anti-hyperglycaemic medications that act to reduce glucose reabsorption in the renal proximal tubules, thereby enhancing urinary glucose excretion. Large randomized placebo-controlled trials in people with diabetes at high cardiovascular risk have demonstrated that SGLT2 inhibitors reduce heart failure hospitalization within months of commencing therapy. These findings are of considerable interest, as diabetes is associated with an increased risk of both heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. In addition, left ventricular (LV) hypertrophy and impaired diastolic function is thought to be more prevalent in people with diabetes. Although many hypotheses have been proposed, the underlying mechanisms through which SGLT2 inhibitors reduce the risk of heart failure in people with diabetes are not fully understood. Given the rapid reduction in heart failure hospitalization, it is conceivable that the benefits of SGLT2 inhibitors are due to favourable haemodynamic and metabolic effects on LV function. Several clinical studies have been conducted to investigate the effect of SGLT2 inhibitors on LV structure and function and have found that LV mass index and diastolic function improve following SGLT2 inhibitor therapy in people with type 2 diabetes. If these findings are confirmed in future studies utilizing novel cardiac imaging modalities and large randomized controlled trials, then this will bring new hope for the prevention and management of heart failure with preserved ejection fraction, for which no current treatments have been shown to reduce mortality. At the present time, SGLT2 inhibitors are indicated for the treatment of type 2 diabetes; however, the results of ongoing trials in participants with heart failure but without diabetes are eagerly awaited. The purpose of this review is to summarize current knowledge regarding the effects of SGLT2 inhibitors on LV function, particularly the findings from clinical studies, proposed biological mechanisms, and future directions.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insuficiência Cardíaca/prevenção & controle , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Técnicas de Imagem Cardíaca/normas , Doenças Cardiovasculares/complicações , Diabetes Mellitus Tipo 2/complicações , Diástole/efeitos dos fármacos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Hospitalização/estatística & dados numéricos , Humanos , Hipertrofia Ventricular Esquerda/epidemiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto , Comportamento de Redução do Risco , Transportador 2 de Glucose-Sódio , Volume Sistólico/efeitos dos fármacos
18.
Eur J Pharmacol ; 860: 172585, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31376367

RESUMO

We previously reported that neonatal blockade of angiotensin II AT1 receptor prevents cardiac changes in 4 weeks rats with neonatal hyperoxia-induced cardiomyopathy, a recognized model of prematurity-related deleterious conditions. Considering the importance of AT1 receptor and the renin angiotensin system (RAS) in normal development, the present study aimed to investigate the adult effects of neonatal AT1 blockade on left ventricle (LV) in rats exposed to neonatal hyperoxia. Sprague-Dawley pups were exposed to 80% O2 or room air from days 3-10. AT1 blocker (losartan) or H2O were given by gavage from day 8-10. LV function (echo and intraventricular pressure), histology and expression of RAS components were examined in 15-16 weeks old adult males. Losartan treatment prevented myocardial fibrosis, LV wall thickening and stroke volume reduction in rats exposed to high O2 in the neonatal period. However, Losartan treatment of O2-exposed pups led to reduced ejection fraction (EF) and fractional shortening (FS), and did not prevent changes in diastolic function. Losartan also did not prevent increased LV AT2 and decreased angiotensin-(1-7) Mas receptors expression observed in high O2-exposed rats. Neonatal Losartan attenuated long-term impact of neonatal hyperoxia but also led to decreased EF and FS. Increased AT2 and decreased Mas receptor expression observed in O2-exposed group were unaffected by Losartan treatment. Our results show that early life Losartan treatment aimed at preventing cardiac consequences of neonatal deleterious conditions may also comprise detrimental effects that require further investigation prior to clinical translation in developing children.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Cardiomiopatias/patologia , Cardiomiopatias/fisiopatologia , Coração/efeitos dos fármacos , Oxigênio/efeitos adversos , Receptor Tipo 1 de Angiotensina/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Biomarcadores/metabolismo , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/metabolismo , Diástole/efeitos dos fármacos , Modelos Animais de Doenças , Fibrose , Coração/fisiopatologia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Losartan/farmacologia , Miocárdio/patologia , Ratos , Ratos Sprague-Dawley , Sístole/efeitos dos fármacos , Fatores de Tempo
19.
J Transl Med ; 17(1): 279, 2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31438970

RESUMO

BACKGROUND: Spaceflight or microgravity conditions cause myocardial atrophy and dysfunction, contributing to post-flight orthostatic intolerance. However, the underlying mechanisms remain incompletely understood and preventive approaches are limited. This study investigated whether and how losartan, a blocker of angiotensin-II receptor, preserved cardiomyocyte size and prevented myocardial dysfunction during microgravity. METHOD: Adult male mice were suspended with their tails to simulate microgravity. Echocardiography was performed to assess myocardial function. Heart weight and cardiomyocyte size were measured. NADPH oxidase activation was determined by analyzing membrane translocation of its cytosolic subunits including p47phox, p67phox and Rac1. Heart tissues were also assayed for oxidative stress, p47phox phosphorylation (Ser345), MuRF1 protein levels and angiotensin-II production. RESULTS: Tail-suspension for 28 days increased angiotensin-II production in hearts, decreased cardiomyocyte size and heart weight, and induced myocardial dysfunction. Administration of losartan preserved cardiomyocyte size and heart weight, and prevented myocardial dysfunction in tail-suspended mice. These cardioprotective effects of losartan were associated with inhibition of p47phox phosphorylation (Ser345), NADPH oxidase and oxidative stress in tail-suspended mouse hearts. Additionally, the NADPH oxidase inhibitor, apocynin, also reduced oxidative stress, preserved cardiomyocyte size and heart weight, and improved myocardial function in tail-suspended mice. Furthermore, losartan but not apocynin attenuated tail-suspension-induced up-regulation of MuRF1 protein in mouse hearts. CONCLUSIONS: Administration of losartan preserves cardiomyocyte size and prevents myocardial dysfunction under microgravity by blocking p47phox phosphorylation and NADPH oxidase activation, and by inhibiting MuRF1 expression. Thus, losartan may be a useful drug to prevent microgravity-induced myocardial abnormalities.


Assuntos
ATPases Associadas a Diversas Atividades Celulares/metabolismo , DNA Helicases/metabolismo , Elevação dos Membros Posteriores , Losartan/administração & dosagem , Proteínas Musculares/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/patologia , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Angiotensina II/metabolismo , Animais , Apelina/metabolismo , Receptores de Apelina/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Tamanho Celular/efeitos dos fármacos , Diástole/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Losartan/farmacologia , Masculino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Valsartana/farmacologia
20.
J Diabetes Complications ; 33(8): 561-566, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31182338

RESUMO

BACKGROUND: People with type 2 diabetes mellitus (T2D) have preclinical cardiac and vascular dysfunction associated with low cardiorespiratory fitness (CRF). This is especially concerning because CRF is a powerful predictor of cardiovascular mortality, a primary issue in T2D management. Glucagon-like pepetide-1 (GLP-1) augments cardiovascular function and our previous data in rodents demonstrate that potentiating the GLP-1 signal with a dipeptidyl peptidase-4 (DPP4) inhibitor augments CRF. Lacking are pharmacological treatments which can target T2D-specific physiological barriers to exercise to potentially permit adaptations necessary to improve CRF and thereby health outcomes in people with T2D. We therefore hypothesized that administration of a DPP4-inhibitor (sitagliptin) would improve CRF in adults with T2D. METHODS AND RESULTS: Thirty-eight participants (64 ±â€¯1 years; mean ±â€¯SE) with T2D were randomized in a double-blinded study to receive 100 mg/day sitagliptin, 2 mg/day glimepiride, or placebo for 3 months after baseline measurements. Fasting glucose decreased with both glimepiride and sitagliptin compared with placebo (P = 0.002). CRF did not change in any group (Placebo: Pre: 15.4 ±â€¯0.9 vs. Post: 16.1 ±â€¯1.1 ml/kg/min vs. Glimepiride: 18.5 ±â€¯1.0 vs. 17.7 ±â€¯1.2 ml/kg/min vs. Sitagliptin: 19.1 ±â€¯1.2 vs. 18.3 ±â€¯1.1 ml/kg/min; P = 0.3). Sitagliptin improved measures of cardiac diastolic function, however, measures of vascular function did not change with any treatment. CONCLUSIONS: Three months of sitagliptin improved diastolic cardiac function, however, CRF did not change. These data suggest that targeting the physiological contributors to CRF with sitagliptin alone is not an adequate strategy to improve CRF in people with T2D. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov NCT01951339.


Assuntos
Aptidão Cardiorrespiratória , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Diástole/efeitos dos fármacos , Inibidores da Dipeptidil Peptidase IV , Fosfato de Sitagliptina/uso terapêutico , Idoso , Glicemia/análise , Diástole/fisiologia , Método Duplo-Cego , Feminino , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Fosforilação Oxidativa , Consumo de Oxigênio , Placebos , Compostos de Sulfonilureia/uso terapêutico
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