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1.
J Sci Food Agric ; 103(1): 428-436, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36373790

RESUMO

BACKGROUND: Our previous study has demonstrated that the egg-white-derived peptide RVPSL can lower blood pressure in spontaneously hypertensive rats (SHRs), but its potential action mechanism remains unclear. In this work, the underlying mechanism of the antihypertensive effects of RVPSL in SHRs was elucidated using the widely targeted kidney metabolomics approach. RESULTS: Ten SHRs were divided into two groups: SHR-Untreated group (0.9% saline) and SHR-RVPSL group (50 mg kg-1 body weight RVPSL) for 4 weeks. After 4 weeks, kidney samples were collected and widely targeted (liquid chromatography-electrospray ionization-tandem mass spectrometry) metabolomics was used to detect metabolites. Fifty-six biomarkers were identified that may be associated with hypertension. Among them, 17 biomarkers were upregulated and 39 biomarkers were downregulated. The results suggested that eight potential biomarkers were identified in kidney samples: O-phospho-l-serine, tyramine, citric acid, 3-hydroxybutyrate, O-acetyl-l-serine, 15-oxo-5Z,8Z,11Z,13E-eicosatetraenoic acid (15-oxoETE), dopaquinone and 3,3',5-triiodo-l-thyronine. These potential biomarkers mainly involved carbon metabolism, thyroid hormone signaling pathway, tyrosine metabolism and arachidonic acid metabolism. CONCLUSION: The study suggested that RVPSL may exert antihypertensive effects through upregulation of O-phospho-l-serine, 3-hydroxybutyrate and 15-oxoETE, and downregulation of tyramine, citric acid, O-acetyl-l-serine, 3,3',5-triiodo-l-thyronine and dopaquinone. The antihypertensive effects of RVPSL may be related to carbon metabolism, thyroid hormone signaling pathway, tyrosine metabolism and arachidonic acid metabolism. RVPSL exhibited a potent antihypertensive effect, and the antihypertensive effects were associated with inhibition of vascular smooth muscle cell proliferation, vascular remodeling, vascular endothelium dysfunction, restoring reactive oxygen species, oxidative stress, inflammation and immune reaction. © 2022 Society of Chemical Industry.


Assuntos
Anti-Hipertensivos , Hipertensão , Ratos , Animais , Anti-Hipertensivos/farmacologia , Ratos Endogâmicos SHR , Ácido Araquidônico , Ácido 3-Hidroxibutírico , Hipertensão/tratamento farmacológico , Metabolômica , Rim , Pressão Sanguínea , Biomarcadores , Serina , Tironinas , Tiramina , Ácido Cítrico , Carbono , Tirosina
2.
J Sci Food Agric ; 103(1): 64-72, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35804485

RESUMO

BACKGROUND: Table olives are a food with a high content of bioactive compounds with cardioprotective properties, such as oleic acid, polyphenols, and pentacyclic triterpenes. Here, we investigate the effect of the intake of table olives on blood pressure (BP) and body weight in spontaneously hypertensive rats (SHR) and their normotensive controls, Wistar Kyoto (WKY) rats. 'Arbequina' table olives (3.85 g kg-1 ) were administered by gavage to SHR and WKY rats in short-term (1 day) and long-term (7 weeks) experiments. BP was measured by the tail-cuff method, and polyphenols and triterpenes were determined in olives and plasma by liquid chromatography-mass spectrometry. RESULTS: Administration of 'Arbequina' olives to WKY rats did not exert any change in BP in any of the experiments. However, in SHR, the single dose induced a transient reduction in BP of approximately 15 mmHg, from the second to the tenth hour after the administration. In the long-term assay, a similar decrease was established in the second week and was maintained throughout the experiment. Moreover, the daily administration of olives to rats did not affect their body weight when compared with controls in either the WKY rats or SHR. The determination of polyphenols and triterpenes in plasma indicated that, at the end of the experiment, only maslinic acid, oleanolic acid, hydroxytyrosol, and luteolin were found, all of them being compounds with already described capacity to decrease BP. CONCLUSION: The results suggest that the daily intake of table olives could decrease BP in hypertension without affecting body weight, indicating that table olives could contribute to improving cardiovascular health. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Hipertensão , Olea , Ratos , Animais , Ratos Endogâmicos SHR , Anti-Hipertensivos/farmacologia , Olea/química , Ratos Endogâmicos WKY , Pressão Sanguínea , Hipertensão/tratamento farmacológico , Polifenóis/farmacologia , Polifenóis/análise , Peso Corporal , Triterpenos Pentacíclicos
3.
JAMA ; 328(18): 1849-1861, 2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36346411

RESUMO

Importance: Hypertension, defined as persistent systolic blood pressure (SBP) at least 130 mm Hg or diastolic BP (DBP) at least 80 mm Hg, affects approximately 116 million adults in the US and more than 1 billion adults worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (coronary heart disease, heart failure, and stroke) and death. Observations: First-line therapy for hypertension is lifestyle modification, including weight loss, healthy dietary pattern that includes low sodium and high potassium intake, physical activity, and moderation or elimination of alcohol consumption. The BP-lowering effects of individual lifestyle components are partially additive and enhance the efficacy of pharmacologic therapy. The decision to initiate antihypertensive medication should be based on the level of BP and the presence of high atherosclerotic CVD risk. First-line drug therapy for hypertension consists of a thiazide or thiazidelike diuretic such as hydrochlorothiazide or chlorthalidone, an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker such as enalapril or candesartan, and a calcium channel blocker such as amlodipine and should be titrated according to office and home SBP/DBP levels to achieve in most people an SBP/DBP target (<130/80 mm Hg for adults <65 years and SBP <130 mm Hg in adults ≥65 years). Randomized clinical trials have established the efficacy of BP lowering to reduce the risk of CVD morbidity and mortality. An SBP reduction of 10 mm Hg decreases risk of CVD events by approximately 20% to 30%. Despite the benefits of BP control, only 44% of US adults with hypertension have their SBP/DBP controlled to less than 140/90 mm Hg. Conclusions and Relevance: Hypertension affects approximately 116 million adults in the US and more than 1 billion adults worldwide and is a leading cause of CVD morbidity and mortality. First-line therapy for hypertension is lifestyle modification, consisting of weight loss, dietary sodium reduction and potassium supplementation, healthy dietary pattern, physical activity, and limited alcohol consumption. When drug therapy is required, first-line therapies are thiazide or thiazidelike diuretics, angiotensin-converting enzyme inhibitor or angiotensin receptor blockers, and calcium channel blockers.


Assuntos
Anti-Hipertensivos , Doenças Cardiovasculares , Hipertensão , Adulto , Humanos , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Bloqueadores dos Canais de Cálcio/farmacologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Diuréticos/uso terapêutico , Hidroclorotiazida/uso terapêutico , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/mortalidade , Hipertensão/terapia , Potássio/uso terapêutico , Redução de Peso
4.
Molecules ; 27(21)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36364149

RESUMO

Cardiovascular diseases (CVD) are the deadliest noncommunicable disease worldwide. Hypertension is the most prevalent risk factor for the development of CVD. Although there is a wide range of antihypertensive drugs, there still remains a lack of blood pressure control options for hypertensive patients. Additionally, natural products remain crucial to the design of new drugs. The natural product 7-hydroxycoumarin (7-HC) exhibits pharmacological properties linked to antihypertensive mechanisms of action. This study aimed to evaluate the vascular effects of 7-HC in an experimental model of essential hypertension. The isometric tension measurements assessed the relaxant effect induced by 7-HC (0.001 µM-300 µM) in superior mesenteric arteries isolated from hypertensive rats (SHR, 200-300 g). Our results suggest that the relaxant effect induced by 7-HC rely on K+-channels (KATP, BKCa, and, to a lesser extent, Kv) activation and also on Ca2+ influx from sarcolemma and sarcoplasmic reticulum mobilization (inositol 1,4,5-triphosphate (IP3) and ryanodine receptors). Moreover, 7-HC diminishes the mesenteric artery's responsiveness to α1-adrenergic agonist challenge and improves the actions of the muscarinic agonist and NO donor. The present work demonstrated that the relaxant mechanism of 7-HC in SHR involves endothelium-independent vasorelaxant factors. Additionally, 7-HC reduced vasoconstriction of the sympathetic agonist while improving vascular endothelium-dependent and independent relaxation.


Assuntos
Hipertensão , Vasodilatação , Ratos , Animais , Canais de Potássio/metabolismo , Hipertensão Essencial , Ratos Endogâmicos SHR , Vasodilatadores/farmacologia , Endotélio Vascular/metabolismo , Anti-Hipertensivos/farmacologia , Umbeliferonas/farmacologia
5.
Nutrients ; 14(21)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36364864

RESUMO

This study aimed to identify the no-observed-adverse-effect level (NOAEL) of dietary epigallocatechin gallate (EGCG) supplementation and its possible antihypertensive and nutrigenomics effects in modulating intrarenal renin-angiotensin system (RAS) gene expression in spontaneously hypertensive rats (SHR). EGCG (50, 250, 500 or 1000 mg/kg b.w. i.g., once daily) was administered to SHR for 28 days. All the SHR survived with no signs of systemic toxicity. Increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and thiobarbituric acid reactive substances (TBARS) were evident in SHR supplemented with 500 and 1000 mg/kg b.w. but not in those supplemented with lower doses of EGCG. Subsequently, the NOAEL of EGCG was established at 250 mg/kg b.w., and the same protocol was replicated to assess its effects on blood pressure and renal RAS-related genes in SHR. The systolic blood pressure (SBP) of the EGCG group was consistently lower than the control group. The mRNA levels of cortical Agtr2 and Ace2 and medullary Agtr2, Ace and Mas1 were upregulated while medullary Ren was downregulated in EGCG group. Statistical analysis showed that SBP reduction was associated with the changes in medullary Agtr2, Ace, and Ren. Dietary EGCG supplementation exhibits antihypertensive and nutrigenomics effects through activation of intrarenal Ace and Agtr2 and suppression of Ren mediators, while a high dose of EGCG induced liver damage in SHR. In future clinical studies, liver damage biomarkers should be closely monitored to further establish the safety of the long-term use of EGCG.


Assuntos
Hipertensão , Sistema Renina-Angiotensina , Ratos , Animais , Ratos Endogâmicos SHR , Anti-Hipertensivos/farmacologia , Hipertensão/metabolismo , Pressão Sanguínea , Suplementos Nutricionais
6.
Nutrients ; 14(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36364890

RESUMO

Hyperkalemia is associated with increased risks of mortality and adverse clinical outcomes. The treatment of hyperkalemia often leads to the discontinuation or restriction of beneficial but potassium-increasing therapy such as renin-angiotensin-aldosterone inhibitors (RAASi) and high-potassium diet including fruits and vegetables. To date, limited evidence is available for personalized risk evaluation in this heterogeneous and multifactorial pathophysiological condition. We developed risk prediction models using extreme gradient boosting (XGB), multiple logistic regression (LR), and deep neural network. Models were derived from a retrospective cohort of hyperkalemic patients with either heart failure or chronic kidney disease stage ≥3a from a Japanese nationwide database (1 April 2008-30 September 2018). Studied outcomes included all-cause death, renal replacement therapy introduction (RRT), hospitalization for heart failure (HHF), and cardiovascular events within three years after hyperkalemic episodes. The best performing model was further validated using an external cohort. A total of 24,949 adult hyperkalemic patients were selected for model derivation and internal validation. A total of 1452 deaths (16.6%), 887 RRT (10.1%), 1,345 HHF (15.4%), and 621 cardiovascular events (7.1%) were observed. XGB outperformed other models. The area under receiver operator characteristic curves (AUROCs) of XGB vs. LR (95% CIs) for death, RRT, HHF, and cardiovascular events were 0.823 (0.805-0.841) vs. 0.809 (0.791-0.828), 0.957 (0.947-0.967) vs. 0.947 (0.936-0.959), 0.863 (0.846-0.880) vs. 0.838 (0.820-0.856), and 0.809 (0.784-0.834) vs. 0.798 (0.772-0.823), respectively. In the external dataset including 86,279 patients, AUROCs (95% CIs) for XGB were: death, 0.747 (0.742-0.753); RRT, 0.888 (0.882-0.894); HHF, 0.673 (0.666-0.679); and cardiovascular events, 0.585 (0.578-0.591). Kaplan-Meier curves of the high-risk predicted group showed a statistically significant difference from that of the low-risk predicted groups for all outcomes (p < 0.005; log-rank test). These findings suggest possible use of machine learning models for real-world risk assessment as a guide for observation and/or treatment decision making that may potentially lead to improved outcomes in hyperkalemic patients while retaining the benefit of life-saving therapies.


Assuntos
Insuficiência Cardíaca , Hiperpotassemia , Adulto , Humanos , Hiperpotassemia/complicações , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Sistema Renina-Angiotensina , Estudos Retrospectivos , Potássio/farmacologia , Insuficiência Cardíaca/complicações , Anti-Hipertensivos/farmacologia , Aprendizado de Máquina
7.
BMJ Open ; 12(11): e064306, 2022 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-36323484

RESUMO

OBJECTIVES: To determine rate of blood pressure (BP) control and to analyse patient-related, medication-related and healthcare system-related factors associated with poor BP control in outpatients with hypertension (HT). DESIGN: Cross-sectional study. SETTING: Two study sites with different levels of healthcare (primary healthcare (PHC) and secondary level of healthcare (SHC)) in Vojvodina, Northern Serbia. PARTICIPANTS: A total of 581 patients (response rate 96.8%) visiting their primary care physician between July 2019 and June 2020 filled out a pretested semistructured questionnaire and had a BP reading during their regular appointments. PRIMARY AND SECONDARY OUTCOME MEASURES: Data on demographics, medication, BP control (target systolic BP≤140 mm Hg and∕ or diastolic BP≤90 mm Hg) and knowledge on HT was collected. Based on the median of knowledge score, patients were classified as having poor, average and adequate knowledge. RESULTS: Majority of the respondents (74.9%) had poorly controlled BP and had HT longer than 10 years. Larger number of patients at PHC site was managed with monotherapy while at the SHC majority received three or more antihypertensive drugs. Respondents from SHC showed a significantly lower knowledge score (9, 2-15) compared with the respondents from PHC (11, 4-15, p=0.001). The share of respondents with adequate knowledge on HT was significantly higher in the group with good BP control (26% and 9.2%, respectively). In a multivariate regression analysis, factors associated with poor BP control were knowledge (B=-1.091; p<0001), number of drugs (B=0536; p<0001) and complications (B=0898; p=0004). CONCLUSIONS: Poor BP control is common in outpatients in Serbia, irrespective of the availability of different levels of healthcare. Patients with poor knowledge on HT, with complications of HT and those with multiple antihypertensive drugs, were at particular risk of poor BP control. Our study could serve as a basis for targeted interventions to improve HT management.


Assuntos
Anti-Hipertensivos , Hipertensão , Humanos , Pressão Sanguínea , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/farmacologia , Estudos Transversais , Pacientes Ambulatoriais , Sérvia/epidemiologia , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Adesão à Medicação
8.
Circ Heart Fail ; 15(11): e009395, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36378759

RESUMO

BACKGROUND: Angiotensin receptor-neprilysin inhibitor (ARNI) prescription in the United States remains suboptimal despite strong evidence for efficacy and value in heart failure with reduced ejection fraction. Factors responsible for under prescription are not completely understood. Economic limitations may play a disproportionate role in reduced access for some patients. METHODS: This is an analysis of the Get With The Guidelines-Heart Failure registry, supplemented with data from the Distressed Community Index. Data were fit to a mixed-effects regression model to investigate clinical and socioeconomic factors associated with ARNI prescription at hospital discharge. Missing data were handled by multilevel multiple imputation. RESULTS: Of the 136 144 patients included in analysis, 12.6% were prescribed an ARNI at discharge. The dominant determinants of ARNI prescription were ARNI use while inpatient (odds ratio [OR], 72 [95% CI, 58-89]; P<0.001) and taking an ARNI before hospitalization (OR 9 [95% CI, 7-13]; P<0.001). Having an ACE (angiotensin-converting enzyme) inhibitor/angiotensin receptor blocker (ARB)/ARNI contraindication was associated with lower likelihood of ARNI prescription at discharge (OR, 0.11 [95% CI, 0.10-0.12]; P<0.001). Socioeconomic factors associated with lower likelihood of ARNI prescription included having no insurance (OR, 0.60 [95% CI, 0.50-0.72]; P<0.001) and living in a ZIP Code identified as distressed (OR, 0.81 [95% CI, 0.70-0.93]; P=0.010). The rate of ARNI prescription is increasing with time (OR, 2 [95% CI, 1.8-2.3]; P<0.001 for patients discharged in 2020 as opposed to 2017), but the disparity in prescription rates between distressed and prosperous communities appears to be increasing. CONCLUSIONS: Multiple medical and socioeconomic factors contribute to low rates of ARNI prescription at hospital discharge. Potential targets for improving ARNI prescription rates include initiating ARNIs during hospitalization and aggressively addressing patients' access barriers with the support of inpatient social services and pharmacists.


Assuntos
Insuficiência Cardíaca , Neprilisina , Humanos , Estados Unidos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Volume Sistólico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Antagonistas de Receptores de Angiotensina/farmacologia , Alta do Paciente , Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Fatores Socioeconômicos , Anti-Hipertensivos/farmacologia , Prescrições , Hospitais
9.
Front Public Health ; 10: 929840, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388284

RESUMO

Background: Heart diseases (HD) are the leading cause of deaths in the world. Many studies have been done on the relationships among hypertension, HD and antihypertensive medications. Most of the studies find that hypertension is a significant risk factor of HD, but there are some studies in which hypertension is not a risk factor. As antihypertensive medications are routinely prescribed to prevent HD, it is necessary to evaluate the effects of these and other risk factors of HD. Data and methods: The relationship between hypertension and HD was analyzed using 6,773,464 medical checkups obtained from the JMDC Claims Database obtained from January 2005 to September 2019. Factors potentially affecting HD, including blood pressures (BP) and usage of antihypertensive medications, were evaluated using 2,861,769 observations. To avoid the causality problem, probit models were used to analyze the probability of an individual who had no history of HD at year t developing HD by year t + 1. Results: A positive relation between systolic blood pressure (SBP) and HD was found in the equation without any other covariates. However, the significant relation between HD and BP disappeared when the models contained various other factors as covariates. When a 10-year age or longer interval was used in the model, a positive relation between the two variables was found, suggesting that SBP works as a proxy variable. Taking antihypertensive medications greatly increases the probability of developing HD in the next year. Higher levels of cholesterols decrease the probability of developing HD. Conclusion: Unlike many previous studies, no significant relationship between HD and hypertension was found in the models containing multiple covariates. The accepted relation might actually be spurious, and it is important to select covariates carefully. Taking antihypertensive medications appears to increase the probability of developing HD in the next year, suggesting the need for further research and greater caution in the use of antihypertensive medications.


Assuntos
Cardiopatias , Hipertensão , Humanos , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/farmacologia , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Pressão Sanguínea , Fatores de Risco , Cardiopatias/complicações , Cardiopatias/tratamento farmacológico
10.
Biomed Pharmacother ; 155: 113796, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36271572

RESUMO

Psidium guajava (guava) leaves extract displays anti-hypertensive properties by mechanisms not yet fully understood. Here, we investigated whether sympathetic drive and immune signaling mechanisms are involved with the antihypertensive effect of the guava extract in a model of salt-dependent hypertension. Raw guava extract (rPsE) was characterized by colorimetric and UPLC-MS techniques. Two doses of rPsE (100 and 200 mg/kg) were evaluated for anti-hypertensive effect using a suspension system (PsE). Weaned male Wistar rats were put on a high-salt diet (HSD, 0.90 % Na+) for 16 weeks and received gavages of PsE for the last 4 weeks. Blood pressure (BP) was measured at the end of treatment in conscious rats. The neurogenic pressor effect was assessed by ganglionic blockade with hexamethonium. Autonomic modulation of heart rate was evaluated by spectral analysis. The effects of orally administered PsE on lumbar sympathetic nerve activity (LSNA) were assessed in anesthetized rats. Blood IL-10, IL-17A, and TNF were measured. The increased neurogenic pressor effect of HSD rats was reduced by PsE 100 mg/kg, but not by 200 mg/kg. PsE (200 mg/kg) administration in anesthetized rats produced a greater fall in BP of HSD rats compared to standard salt diet (SSD) rats. PsE hypotensive response elicited an unproportionable increase in LSNA of HSD rats compared to SSD rats. PsE (200 mg/kg) increased plasma concentrations of IL-10 but had no effect on TNF or IL-17A. Our data indicate that the antihypertensive effects of PsE may involve autonomic mechanisms and immunomodulation by overexpression of IL-10 in salt-dependent hypertensive rats.


Assuntos
Hipertensão , Psidium , Ratos , Masculino , Animais , Pressão Sanguínea , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Interleucina-17/farmacologia , Hexametônio/farmacologia , Hexametônio/uso terapêutico , Interleucina-10 , Cromatografia Líquida , Ratos Wistar , Espectrometria de Massas em Tandem , Hipertensão/tratamento farmacológico , Cloreto de Sódio na Dieta , Folhas de Planta , Cloreto de Sódio , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
11.
Biomed Pharmacother ; 155: 113802, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36271577

RESUMO

Allicin is the main active component of Traditional Chinese medicine, garlic. It is widely used to treat cardiovascular diseases. Our previous studies have confirmed that allicin significantly reduces blood pressure in Spontaneous Hypertension Rats (SHRs). However, the reports studying the effect of allicin on vascular and cardiac remodeling caused by hypertension are few, with their underlying mechanism not being studied in detail or fully elucidated. In this study, we treated 12-week-old SHRs with allicin for 4 weeks. After 4 weeks, allicin was shown to improve vascular and cardiac remodeling in SHRs, as evidenced by reduced cardiac left ventricular wall thickness, aortic vessel thickness, and reduced proliferating cell nuclear antigen (PCNA) and smooth muscle actin (α-SMA), and increased expression of and smooth muscle 22α (SM 22α). Additionally, allicin reduced serum IL-1ß, IL-6, and TNF-α levels, improved calcium homeostasis in cardiomyocytes, downregulated calcium transportation-related CaMK II and inflammation-related NF-κB and NLRP3, which were observed in smooth muscle cells and cardiomyocytes. Thus, we inferred that allicin protected hypertensive vascular and cardiac remodeling in Spontaneous Hypertensive Rats by inhibiting the activation of the CaMK II/ NF-κB pathway. This study also provided new mechanistic insights into the anti-hypertensive vascular and cardiac remodeling effects of allicin, highlighting its therapeutic potential.


Assuntos
Hipertensão , NF-kappa B , Ratos , Animais , NF-kappa B/metabolismo , Antígeno Nuclear de Célula em Proliferação , Actinas , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Remodelação Ventricular , Fator de Necrose Tumoral alfa , Proteína 3 que Contém Domínio de Pirina da Família NLR , Interleucina-6 , Cálcio , Ratos Endogâmicos SHR , Hipertensão/tratamento farmacológico
12.
Molecules ; 27(20)2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36296487

RESUMO

The alkaloid Aspidocarpine was isolated from the bark of Aspidosperma desmanthum. Its structure was elucidated by the spectral data of 1H and 13C-NMR (1D and 2D) and high-resolution mass spectrometry (HRESIMS). The antihypertensive activity was investigated by intravenous infusion in Wistar rats. This alkaloid significantly reduced (p < 0.05) the systolic, median, and diastolic blood pressures of rodents, without causing motor incoordination and imbalance in the rotarod test. The results indicate that the alkaloid Aspidocarpine exerts its antihypertensive activity without causing sedation or the impairment of motor functions.


Assuntos
Alcaloides , Aspidosperma , Ratos , Animais , Ratos Wistar , Anti-Hipertensivos/farmacologia , Alcaloides Indólicos/química , Aspidosperma/química , Alcaloides/farmacologia
13.
J Clin Hypertens (Greenwich) ; 24(9): 1121-1138, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36196473

RESUMO

Hypertension is uncontrolled in over 50% hypertensive population in Vietnam which indicated a compelling need for new hypertension guidelines. The highlights were composed of three parts: the diagnosis of arterial hypertension, the recommendation of home blood pressure monitoring, and the treatment of hypertension. Our guideline applied flexibility based upon the "essential" and "optimal" concepts in the diagnosis and management of hypertensive patients according to the socio-economic status of Vietnam. Hypertension is defined as an office systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg which is equivalent to a 24-hr ambulatory blood pressure monitoring average of ≥130/80 mmHg or home blood pressure monitoring average of ≥135/85 mmHg. We established an integrated hypertensive diagnostic algorithm for adults with the optimal option by the role of out-of-office blood pressure measurement, especially home blood pressure monitoring, which is fully recommended in this guideline. The threshold and target of hypertension treatment were individualized in safety range and effective evidence-based medicine. We also update for the management of resistant hypertension, hypertension in diabetic patients, hypertension with heart failure, and with other comorbidities. Vietnam has tried on the best strategy for improving the control of hypertension and recently received several achievements in the world, especially in the Asian region. Because the conditions for conducting our national data have not been fully conducted, we have to adapt from existing guidelines so there are still certain limitations that need to be supplemented and adjusted in the upcoming version.


Assuntos
Hipertensão , Adulto , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Asiáticos , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Vietnã/epidemiologia
14.
J Clin Hypertens (Greenwich) ; 24(9): 1180-1186, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36196467

RESUMO

There is emerging evidence that α1-blockers can be safely used in the treatment of hypertension. These drugs can be used in almost all hypertensive patients for blood pressure control. However, there are several special indications. Benign prostatic hyperplasia is a compelling indication of α1-blockers, because of the dual treatment effect on both high blood pressure and lower urinary tract symptoms. Many patients with resistant hypertension would require α1-blockers as add-on therapy. Primary aldosteronism screen is a rapidly increasing clinical demand in the management of hypertension, where α1-blockers are useful for blood pressure control in the preparation for the measurement of plasma aldosterone and renin. Nonetheless, α1-blockers have to be used under several considerations. Among the currently available agents, only long-acting α1-blockers, such as doxazosin gastrointestinal therapeutic system 4-8 mg daily and terazosin 2-4 mg daily, should be chosen. Orthostatic hypotension is a concern with the use of α1-blockers especially in the elderly, and requires careful initial bedtime dosing and avoiding overdosing. Fluid retention is potentially also a concern, which may be overcome by combining an α1-blocker with a diuretic.


Assuntos
Hipertensão , Antagonistas Adrenérgicos alfa/uso terapêutico , Idoso , Aldosterona , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Diuréticos/uso terapêutico , Doxazossina/uso terapêutico , Humanos , Hipertensão/tratamento farmacológico , Renina
15.
J Clin Hypertens (Greenwich) ; 24(9): 1174-1179, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36196474

RESUMO

High blood pressure (BP) confers cardiovascular risk. However, the clinical value of central BP remains debatable. In this article, we aim to briefly review the prognosis, diagnosis, and treatment of central hypertension. Central and brachial BPs are closely correlated. In most prospective investigations, elevated central and peripheral BPs were similarly associated with adverse outcomes. Outcome-driven thresholds of the central systolic BP estimated by the type I device were on average 10 mmHg lower than their brachial counterparts. Cross-classification based on the central and brachial BPs identified that nearly 10% of patients had discrepancy in their status of central and brachial hypertension. Irrespective of the brachial BP status, central hypertension was associated with increased cardiovascular risk, highlighting the importance of central BP assessment in the management of hypertensive patients. Newer antihypertensive agents, such as renin-angiotensin-aldosterone system inhibitors and calcium channel blockers, were more efficacious than older agents in central BP reduction. Clinical trials are warranted to demonstrate whether controlling central hypertension with an optimized antihypertensive drug treatment will be beneficial beyond the control of brachial hypertension.


Assuntos
Doenças Cardiovasculares , Hipertensão , Anti-Hipertensivos/farmacologia , Pressão Sanguínea , Bloqueadores dos Canais de Cálcio/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Fatores de Risco de Doenças Cardíacas , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Estudos Prospectivos , Fatores de Risco
16.
Eur Rev Med Pharmacol Sci ; 26(20): 7482-7492, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36314318

RESUMO

OBJECTIVE: The aim of the study was to review the literature on clinical pharmacology of lercanidipine and experimental and clinical evidence and evaluate its ability to reduce proteinuria and preserve renal function when used as monotherapy or in combination with the angiotensin-converting enzyme (ACE) inhibitor enalapril. MATERIALS AND METHODS: MEDLINE/PubMed was searched for appropriate keywords. RESULTS: Lercanidipine, a third-generation calcium channel blocker, has been shown to have a unique pharmacological and clinical profile, which translates into favorable renal hemodynamic changes. The fixed-dose combination lercanidipine/enalapril has been proposed to overcome unmet therapeutic needs, often as the initial treatment in the high-risk patient. CONCLUSIONS: Lercanidipine may be regarded as an ideal antihypertensive drug for patients at renal risk and possibly the preferred choice among calcium channel blocker drugs.


Assuntos
Anti-Hipertensivos , Hipertensão , Humanos , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Enalapril/farmacologia , Enalapril/uso terapêutico , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Rim , Pressão Sanguínea
17.
Ren Fail ; 44(1): 1811-1818, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36285374

RESUMO

BACKGROUND: Hypertension is a leading preventable risk factor for cardiovascular disease in hemodialysis patients. Pre-dialysis systolic blood pressure (SBP) more than 160 mmHg was thought to be associated with increased risk of cardiovascular events and all-cause mortality. The present study was performed to explore the clinical characteristics and management of hemodialysis patients with pre-dialysis SBP ≥ 160 mmHg. METHODS: A total of 1233 patients undergoing hemodialysis from nine hemodialysis centers were enrolled. Pre-dialysis and home BP were measured and clinical data were collected. The characteristics of patients with pre-dialysis SBP ≥ 160 mmHg were explored. Clinical parameters between hypertensive and non-hypertensive patients were compared. The partial correlation analyses performed to identify the associations between BP and clinical parameters. RESULTS: There were 24.6% of the hemodialysis patients had pre-dialysis SBP ≥ 160 mmHg and the average SBP was 173.8 ± 10.9 mmHg. Only 21.4% of the patients achieved dry weight after dialysis and up to 30.2% of patients were not given combination therapies of antihypertensive drugs. Compared to patients with pre-hemodialysis SBP < 160 mmHg, patients with pre-dialysis SBP ≥ 160 mmHg had lower target-reaching rate of Kt/v and higher incidences of intradialytic hypotension and muscle spasm. Most patients (96%) with pre-dialysis SBP ≥ 160 mmHg had home SBP≥ 135 mmHg. Patients with home SBP ≥ 160 mmHg had higher left ventricular weight index and lower hemoglobin levels when compared to their counterparts with home SBP <160 mmHg. CONCLUSIONS: Pre-dialysis SBP ≥ 160 mmHg is common in clinical practice and most of the patients could diagnosed to be hypertensive according to their home SBP. Patients with pre-dialysis SBP ≥ 160 mmHg are more likely to be subjected to dialysis insufficiency and intradialytic complications. Achieving dry weight and sufficient pharmacologic interventions should be strengthened to improve BP control in the hemodialysis population.


Assuntos
Anti-Hipertensivos , Hipertensão , Humanos , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/farmacologia , Diálise , Hipertensão/etiologia , Hipertensão/complicações , Diálise Renal/efeitos adversos , Pressão Sanguínea , Hemoglobinas
18.
Nat Med ; 28(10): 2056-2065, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36216934

RESUMO

High systolic blood pressure (SBP) is a major risk factor for ischemic heart disease (IHD), the leading cause of death worldwide. Using data from published observational studies and controlled trials, we estimated the mean SBP-IHD dose-response function and burden of proof risk function (BPRF), and we calculated a risk outcome score (ROS) and corresponding star rating (one to five). We found a very strong, significant harmful effect of SBP on IHD, with a mean risk-relative to that at 100 mm Hg SBP-of 1.39 (95% uncertainty interval including between-study heterogeneity 1.34-1.44) at 120 mm Hg, 1.81 (1.70-1.93) at 130 mm Hg and 4.48 (3.81-5.26) at 165 mm Hg. The conservative BPRF measure indicated that SBP exposure between 107.5 and 165.0 mm Hg raised risk by 101.36% on average, yielding a ROS of 0.70 and star rating of five. Our analysis shows that IHD risk was already increasing at 120 mm Hg SBP, rising steadily up to 165 mm Hg and increasing less steeply above that point. Our study endorses the need to prioritize and strengthen strategies for screening, to raise awareness of the need for timely diagnosis and treatment of hypertension and to increase the resources allocated for understanding primordial prevention of elevated blood pressure.


Assuntos
Hipertensão , Isquemia Miocárdica , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Humanos , Hipertensão/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/epidemiologia , Espécies Reativas de Oxigênio
19.
J Clin Hypertens (Greenwich) ; 24(11): 1436-1443, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36225118

RESUMO

The aim of the study was to assess drug adherence, as well as association of psychological factors with both drug adherence and severity of hypertension in two subtypes of patients with apparently treatment-resistant hypertension (ATRH): younger patients with uncomplicated hypertension (YURHTN) versus patients ≥60-year-old and/or with a history of cardio- or cerebrovascular complication (OCRHTN). Drug adherence was assessed in urine by targeted Liquid Chromatography-Mass Spectrometry. The severity of hypertension was assessed by 24-h ambulatory blood pressure adjusted for the number of antihypertensive drugs and for drug adherence. Psychological profile was assessed using five validated questionnaires. The proportion of totally non-adherent patients was three times higher (24.1 vs. 7.1%, P = 0.026) in the YURHTN (n = 54) than in OCRHTN subgroup (n = 43). Independent predictors of drug adherence in YURHTN were ability to use adaptive strategies, male sex and family history of hypertension, accounting for 39% of variability in drug adherence. In the same subgroup, independent predictors of severity of hypertension were somatization and lower recourse to planification, accounting for 40% of variability in the severity of hypertension. In contrast, in the OCRHTN subgroup, independent predictors of drug adherence and severity of hypertension were limited to the number of yearly admissions to the emergency room and the total number of prescribed drugs. In conclusion, poor drug adherence and altered psychological profiles appear to play a major role in younger patients with ATRH devoid of cardiovascular complication. This subgroup should be prioritized for chemical detection of drug adherence and psychological evaluation.


Assuntos
Hipertensão , Humanos , Masculino , Pessoa de Meia-Idade , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/diagnóstico , Monitorização Ambulatorial da Pressão Arterial , Anti-Hipertensivos/farmacologia , Adesão à Medicação , Cromatografia Líquida/métodos , Pressão Sanguínea
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