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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.
Life Sci ; 266: 118888, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33310031

RESUMO

AIMS: Peroxisome proliferator-activated receptor (PPAR) α, a key regulator of lipid metabolism, plays a role in maintaining the homeostasis of myocardial energy metabolism. Both hypoxia and obesity inhibit the expression of PPARα in the myocardium. In this study, we verified the inhibitory effects of hypoxia and obesity on PPARα and examined whether WY14643 (4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid), an agonist of PPARα, ameliorates myocardial mitochondrial dysfunction and protects cardiac function in obese rats under chronic persistent hypoxia. MAIN METHODS: Sprague-Dawley rats were randomly divided into six groups: a control group (normal chow diet, normal oxygen), a high-fat diet (HFD) group (normal oxygen), a chronic persistent hypoxia normal chow diet group, a chronic persistent hypoxia HFD group, a chronic persistent hypoxia HFD group with WY14643 treatment, and a chronic persistent hypoxia HFD group with vehicle treatment. KEY FINDINGS: Hypoxia and obesity increased myocardial lipid accumulation, mitochondrial dysfunction, and left ventricular systolic dysfunction. Myocardial lipid metabolism-related genes, including those encoding PPARα, PPARγ coactivator 1α (PGC1α), and carnitine palmitoyl transferase 1α (CPT1α), were downregulated, while acetyl-CoA carboxylase 2 (ACC2) was upregulated under a combination of hypoxia and obesity. WY14643 upregulated PPARα, PGC1α, and CPT1α, and downregulated ACC2. WY14643 alleviated hypoxia- and obesity-induced myocardial lipid accumulation and improved mitochondrial and left ventricular systolic functions. SIGNIFICANCE: WY14643 improved myocardial mitochondrial and left ventricular systolic functions in obese rats under chronic persistent hypoxia. Thus, WY14643 possibly exerts its effects by regulating the PPARα pathway and shows potential as a therapeutic target for cardiovascular diseases associated with obesity and hypoxia.


Assuntos
Hipóxia/fisiopatologia , Mitocôndrias Cardíacas/efeitos dos fármacos , Obesidade/fisiopatologia , PPAR alfa/agonistas , Pirimidinas/farmacologia , Sístole/efeitos dos fármacos , Disfunção Ventricular Esquerda/tratamento farmacológico , Animais , Masculino , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Pirimidinas/química , Ratos , Ratos Sprague-Dawley , Volume Sistólico , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/patologia
3.
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
4.
PLoS One ; 15(8): e0238039, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32853284

RESUMO

Sepsis is a global economic and health burden. Dipeptidyl peptidase 3 (DPP3) is elevated in the plasma of septic patients. The highest levels of circulating DPP3 (cDPP3) are found in non-survivor septic shock patients. The aim of this study was to evaluate the benefits of inhibiting cDPP3 by a specific antibody, Procizumab (PCZ), on cardiac function in an experimental model of sepsis, the caecal ligature and puncture (CLP) model. Rats were monitored by invasive blood pressure and echocardiography. Results are presented as mean ± SD, with p <0.05 considered significant. PCZ rapidly restored left ventricular shortening fraction (from 39 ± 4% to 51 ± 2% before and 30 min after PCZ administration (p = 0.004)). Cardiac output and stroke volume were higher in the CLP + PCZ group when compared to the CLP + PBS group (152 ± 33 mL/min vs 97 ± 25 mL/min (p = 0.0079), and 0.5 ± 0.1 mL vs 0.3 ± 1.0 mL (p = 0.009), respectively) with a markedly reduced plasma DPP3 activity (138 ± 70 U/L in CLP + PCZ group versus 735 ± 255 U/L (p = 0.048) in the CLP + PBS group). Of note, PCZ rapidly reduced oxidative stress in the heart of the CLP + PCZ group when compared to those of the CLP + PBS group (13.3 ± 8.2 vs 6.2 ± 2.5 UI, p = 0.005, 120 min after administration, respectively). Our study demonstrates that inhibition of cDPP3 by PCZ restored altered cardiac function during sepsis in rats.


Assuntos
Dipeptidil Peptidases e Tripeptidil Peptidases/antagonistas & inibidores , Dipeptidil Peptidases e Tripeptidil Peptidases/sangue , Inibidores Enzimáticos/farmacologia , Coração/efeitos dos fármacos , Coração/fisiopatologia , Sepse/sangue , Sepse/fisiopatologia , Animais , Modelos Animais de Doenças , Hemodinâmica/efeitos dos fármacos , Masculino , Estudo de Prova de Conceito , Ratos , Ratos Wistar , Sepse/enzimologia , Sístole/efeitos dos fármacos , Sístole/fisiologia
5.
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
6.
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
7.
Biochem Biophys Res Commun ; 523(4): 867-873, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-31955888

RESUMO

Inflammation is centrally involved in the development of cardiac hypertrophy and the processes of remodelling. The complement system and Toll-like receptor (TLR) family, two upstream arms of the innate immune system, have previously been reported to be involved in cardiac remodelling. However, the role of complement component 3 (C3), TLR co-receptor CD14 and the synergy between them have not been addressed during pressure overload-induced cardiac remodelling. Here, we examined angiotensin II-induced cardiac hypertrophy and remodelling for 7 days in male C57Bl/6 J mice deficient in C3, CD14, or both (C3CD14), and WT controls. Angiotensin II infusion induced a mild concentric hypertrophic phenotype in WT mice with increased left ventricle weight, wall thicknesses and reduced ventricular internal diameter, associated with increased cardiac fibrosis. However, there were no differences between WT mice and mice deficient for C3, CD14 or C3CD14, as systolic blood pressure, cardiac function and structure and levels of fibrosis were comparable between WT mice and the three other genotypes. C5a did not change in angiotensin II treated mice, whereas Mac2 levels were increased in angiotensin II treated mice, but did not differ between genotypes. The inflammatory IL-6 response was comparable between WT and C3 deficient mice, however, it was decreased in CD14 and C3CD14 deficient mice. We conclude that deficiency in C3, CD14 or C3CD14 had no effect on cardiac remodelling following angiotensin II-induced pressure overload. This suggests that C3 and CD14 are not involved in angiotensin II-induced adverse cardiac remodelling.


Assuntos
Angiotensina II/farmacologia , Complemento C3/metabolismo , Receptores de Lipopolissacarídeos/metabolismo , Receptores Toll-Like/metabolismo , Remodelação Ventricular/efeitos dos fármacos , Animais , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Cardiomegalia/sangue , Cardiomegalia/genética , Fibrose , Hipertrofia , Interleucina-6/genética , Interleucina-6/metabolismo , Camundongos , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Tamanho do Órgão/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sístole/efeitos dos fármacos
8.
Am Heart J ; 220: 264-272, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31923768

RESUMO

BACKGROUND: Bereavement is associated with an increased risk of cardiovascular disease; however, no reports exist of interventions to reduce risk. In a randomized, double-blind, placebo-controlled trial of 85 recently bereaved participants, we determined whether ß-blocker (metoprolol 25 mg) and aspirin (100 mg) reduce cardiovascular risk markers and anxiety, without adversely affecting bereavement intensity. METHODS: Participants were spouses (n = 73) or parents (n = 12) of deceased from 5 hospitals in Sydney, Australia, 55 females, 30 males, aged 66.1 ±â€¯9.4 years. After assessment within 2 weeks of bereavement, subjects were randomized to 6 weeks of daily treatment or placebo, and the effect evaluated using ANCOVA, adjusted for baseline values (primary analysis). RESULTS: Participants on metoprolol and aspirin had lower levels of home systolic pressure (P = .03), 24-hour average heart rate (P < .001) and anxiety (P = .01) platelet response to arachidonic acid (P < .001) and depression symptoms (P = .046) than placebo with no difference in standard deviation of NN intervals index (SDNNi), von Willebrand Factor antigen, platelet-granulocyte aggregates or bereavement intensity. No significant adverse safety impact was observed. CONCLUSIONS: In early bereavement, low dose metoprolol and aspirin for 6 weeks reduces physiological and psychological surrogate measures of cardiovascular risk. Although further research is needed, results suggest a potential preventive benefit of this approach during heightened cardiovascular risk associated with early bereavement.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Luto , Doenças Cardiovasculares/prevenção & controle , Metoprolol/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/tratamento farmacológico , Ácido Araquidônico/farmacologia , Plaquetas/efeitos dos fármacos , Depressão/tratamento farmacológico , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Conduta do Tratamento Medicamentoso , Pessoa de Meia-Idade , Placebos , Estudos Prospectivos , Sístole/efeitos dos fármacos
10.
Sci Rep ; 9(1): 19351, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852920

RESUMO

GLP-1 receptor agonists (GLP-1RA) and SGLT2 inhibitors (SGLT2i) have been associated with improved glycemic control, body weight loss and favorable changes in cardiovascular risk factors and outcomes. We conducted a systematic review and meta-analysis to evaluate the effects of the addition of GLP-1RA to SGLT2i in patients with type 2 diabetes mellitus and inadequate glycemic control. Six databases were searched until March 2019. Randomized controlled trials (RCT) with a follow-up of at least 24 weeks reporting on HbA1c, body weight, systolic blood pressure, lipids, achievement of HbA1c < 7%, requirement of rescue therapy due to hyperglycemia and hypoglycemic events were selected. Four RCTs were included. Compared to SGLT2i, the GLP-1RA/SGLT2i combination was associated with greater reduction in HbA1c (-0.74%), body weight (-1.61 kg), and systolic blood pressure (-3.32 mmHg). A higher number of patients achieved HbA1c < 7% (RR = 2.15), with a lower requirement of rescue therapy (RR = 0.37) and similar incidence of hypoglycemia. Reductions in total and LDL cholesterol were found. The present review supports treatment intensification with GLP-1RA in uncontrolled type 2 diabetes on SGLT2i. This drug regimen could provide improved HbA1c control, together with enhanced weight loss and blood pressure and lipids control.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Hemoglobina A Glicada/metabolismo , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Sístole/efeitos dos fármacos , Resultado do Tratamento
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
13.
J Clin Hypertens (Greenwich) ; 21(12): 1813-1820, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31670874

RESUMO

This was a post hoc analysis of Systolic Blood Pressure Intervention Trial (SPRINT), aimed to investigate whether intensive blood pressure treatment has differential therapeutic outcomes on patients with different baseline Framingham risk score (FRS). The 9298 SPRINT participants were categorized into low-risk (baseline FRS < 10%), intermediate-risk (FRS = 10%-20%), or high-risk (FRS > 20%) arms. The primary outcome was a composite of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes. Serious adverse events were defined as hypotension, syncope, and bradycardia. Multiple Cox regression was used to calculate hazard ratios for study outcomes with intensive compared with standard SBP treatment between these three groups. After a median follow-up time of 3.26 years, the primary outcome hazard ratio (HR) for intensive versus standard treatment was 0.73 (95% CI: 0.61-0.88, P = .0044) in the high-risk arm. And, for all-cause mortality, the hazard ratio with intensive SBP treatment was 1.58 (95% CI: 0.55-1.06), 0.9 (95% CI: 0.26-9.50), and 0.53 (95% CI: 0.34-0.82) in three arms (all P values for interaction > 0.05). Effects of intensive versus standard SBP control on serious adverse events were similar among patients with different FRS. Our results suggested that regardless of the FRS level, the intensive blood pressure control was beneficial.


Assuntos
Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea/fisiologia , Hipertensão/tratamento farmacológico , Sístole/efeitos dos fármacos , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/epidemiologia , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Bradicardia/induzido quimicamente , Bradicardia/epidemiologia , Estudos de Casos e Controles , Morte , Feminino , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Hipotensão/induzido quimicamente , Hipotensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Modelos de Riscos Proporcionais , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Síncope/induzido quimicamente , Síncope/epidemiologia , Resultado do Tratamento
15.
Biomed Pharmacother ; 120: 109539, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31627089

RESUMO

BACKGROUND: Most antihypertensive drugs used in monotherapy or in combination therapy reduce the left ventricular mass index (LVMI). However, little is known about the effects on LVMI of a triple fixed-dose combination (TFC) therapy, containing in a single pill an angiotensin-converting enzyme inhibitor (ACEI), a diuretic and a calcium channel blocker (CCB). METHODS: In this prospective open-label study, 92 patients with essential hypertension were randomized to treatment with a TFC of perindopril/indapamide/amlodipine at different doses or a triple free combination therapy (FCT) including ACEI/diuretic/CCB. Office blood pressure (BP) measurement, 24 h-ambulatory BP monitoring and echocardiography were performed at baseline and during a 14-month follow-up. The BP variability (BPV) over 24 h was calculated as ± standard deviation of the daytime systolic BP. Differences between office and monitored BP and LVMI were evaluated by ANOVA for repeated measures. RESULTS: A significant BP-lowering effect was observed for both treatments. At follow-up, BPV was reduced in both the treatment groups vs. the baseline (14.0±1.5 vs. 17.0±1.8 and 16.2±2.1 vs. 17.6±2.3, respectively), but it was lower in the TFC vs. the FCT group (14.0±1.5 vs. 16.1±2.2, P < 0.05). LVMI was lower in both the treatment groups, but the change was greater for TFC vs. FCT (-8.3±4.9% vs. -2.0 ±2.1%, P < 0.0001). Left ventricular hypertrophy (LVH) regression was greater in the TFC vs. the FCT group (43.5% vs. 30.4%, P < 0.05). CONCLUSIONS: Independently of BP values achieved, the antihypertensive TFC therapy was more effective than FCT in LVMI reduction and LVH regression, possibly related to drugs' intrinsic properties and to BPV modulation.


Assuntos
Anlodipino/uso terapêutico , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertrofia Ventricular Esquerda/complicações , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Indapamida/uso terapêutico , Pacientes Ambulatoriais , Perindopril/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Monitorização Ambulatorial da Pressão Arterial , Combinação de Medicamentos , Feminino , Seguimentos , Humanos , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Sístole/efeitos dos fármacos , Fatores de Tempo
16.
Int J Mol Sci ; 20(18)2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31514290

RESUMO

In salt-sensitive hypertension, reactive oxygen species (ROS) play a major role in the progression of renal disease partly through the activation of the mineralocorticoid receptor (MR). We have previously demonstrated that urinary vanin-1 is an early biomarker of oxidative renal tubular injury. However, it remains unknown whether urinary vanin-1 might reflect the treatment effect. The objective of this study was to clarify the treatment effect for renal tubular damage in Dahl salt-sensitive (DS) rats. DS rats (six weeks old) were given one of the following for four weeks: high-salt diet (8% NaCl), high-salt diet plus a superoxide dismutase mimetic, tempol (3 mmol/L in drinking water), high-salt diet plus eplerenone (100 mg/kg/day), and normal-salt diet (0.3% NaCl). After four-week treatment, blood pressure was measured and kidney tissues were evaluated. ROS were assessed by measurements of malondialdehyde and by immunostaining for 4-hydroxy-2-nonenal. A high-salt intake for four weeks caused ROS and histological renal tubular damages in DS rats, both of which were suppressed by tempol and eplerenone. Proteinuria and urinary N-acetyl-ß-D-glucosaminidase exhibited a significant decrease in DS rats receiving a high-salt diet plus eplerenone, but not tempol. In contrast, urinary vanin-1 significantly decreased in DS rats receiving a high-salt diet plus eplerenone as well as tempol. Consistent with these findings, immunohistochemical analysis revealed that vanin-1 was localized in the renal proximal tubules but not the glomeruli in DS rats receiving a high-salt diet, with the strength attenuated by tempol or eplerenone treatment. In conclusion, these results suggest that urinary vanin-1 is a potentially sensitive biomarker for ameliorating renal tubular damage in salt-sensitive hypertension.


Assuntos
Amidoidrolases/metabolismo , Túbulos Renais/patologia , Estresse Oxidativo , Amidoidrolases/urina , Animais , Biomarcadores/sangue , Biomarcadores/urina , Pressão Sanguínea/efeitos dos fármacos , Óxidos N-Cíclicos/farmacologia , Eplerenona/farmacologia , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/fisiopatologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Endogâmicos Dahl , Marcadores de Spin , Sístole/efeitos dos fármacos
17.
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
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.
PLoS One ; 14(8): e0221798, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31461499

RESUMO

BACKGROUND: Diabetic cardiomyopathy (DM CMP) is defined as cardiomyocyte damage and ventricular dysfunction directly associated with diabetes independent of concomitant coronary artery disease or hypertension. Matrix metalloproteinases (MMPs), especially MMP-2, have been reported to underlie the pathogenesis of DM CMP by increasing extracellular collagen content. PURPOSE: We hypothesized that two discrete MMP-2 isoforms (full length MMP-2, FL-MMP-2; N-terminal truncated MMP-2, NTT-MMP-2) are induced by high glucose stimulation in vitro and in an experimental diabetic heart model. METHODS: Rat cardiomyoblasts (H9C2 cells) were examined to determine whether high glucose can induce the expression of the two isoforms of MMP-2. For the in vivo study, we used the streptozotocin-induced DM mouse heart model and age-matched controls. The changes of each MMP-2 isoform expression in the diabetic mice hearts were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical stains were conducted to identify the location and patterns of MMP-2 isoform expression. Echocardiography was performed to compare and analyze the changes in cardiac function induced by diabetes. RESULTS: Quantitative RT-PCR and immunofluorescence staining showed that the two MMP-2 isoforms were strongly induced by high glucose stimulation in H9C2 cells. Although no definite histologic features of diabetic cardiomyopathy were observed in diabetic mice hearts, left ventricular systolic dysfunction was determined by echocardiography. Quantitative RT-PCR and IHC staining showed this abnormal cardiac function was accompanied with the increases in the mRNA levels of the two isoforms of MMP-2 and related to intracellular localization. CONCLUSION: Two isoforms of MMP-2 were induced by high glucose stimulation in vitro and in a Type 1 DM mouse heart model. Further study is required to examine the role of these isoforms in DM CMP.


Assuntos
Diabetes Mellitus Experimental/enzimologia , Metaloproteinase 2 da Matriz/metabolismo , Miocárdio/enzimologia , Animais , Linhagem Celular , Glucose/toxicidade , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Isoenzimas/metabolismo , Camundongos Endogâmicos C57BL , Mitocôndrias Cardíacas/ultraestrutura , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/ultraestrutura , Ratos , Sístole/efeitos dos fármacos
20.
BMC Anesthesiol ; 19(1): 125, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31288740

RESUMO

BACKGROUND: Renal dysfunction following intraoperative arterial hypotension is mainly caused by an insufficient renal blood flow. It is associated with higher mortality and morbidity rates. We hypothesised that the intraoperative haemodynamics are more stable during xenon anaesthesia than during isoflurane anaesthesia in patients undergoing partial nephrectomy. METHODS: We performed a secondary analysis of the haemodynamic variables collected during the randomised, single-blinded, single-centre PaNeX study, which analysed the postoperative renal function in 46 patients who underwent partial nephrectomy. The patients received either xenon or isoflurane anaesthesia with 1:1 allocation ratio. We analysed the duration of the intraoperative systolic blood pressure decrease by > 40% from baseline values and the cumulative duration of a mean arterial blood pressure (MAP) of < 65 mmHg as primary outcomes. The secondary outcomes were related to other blood pressure thresholds, the amount of administered norepinephrine, and the analysis of confounding factors on the haemodynamic stability. RESULTS: The periods of an MAP of < 65 mmHg were significantly shorter in the xenon group than in the isoflurane group. The medians [interquartile range] were 0 [0-10.0] and 25.0 [10.0-47.5] minutes, for the xenon and isoflurane group, respectively (P = 0.002). However, the cumulative duration of a systolic blood pressure decrease by > 40% did not significantly differ between the groups (P = 0.51). The periods with a systolic blood pressure decrease by 20% from baseline, MAP decrease to values < 60 mmHg, and the need for norepinephrine, as well as the cumulative dose of norepinephrine were significantly shorter and lower, respectively, in the xenon group. The confounding factors, such as demographic data, surgical technique, or anaesthesia data, were similar in the two groups. CONCLUSION: The patients undergoing xenon anaesthesia showed a better haemodynamic stability, which might be attributed to the xenon properties. The indirect effect of xenon anaesthesia might be of importance for the preservation of renal function during renal surgery and needs further elaboration. TRIAL REGISTRATION: ClinicalTrials.gov : NCT01839084. Registered 24 April 2013.


Assuntos
Anestésicos Inalatórios/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Isoflurano/farmacologia , Monitorização Intraoperatória , Xenônio/farmacologia , Relação Dose-Resposta a Droga , Feminino , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Nefrectomia , Norepinefrina/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Sístole/efeitos dos fármacos , Vasoconstritores/administração & dosagem
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