RESUMEN
Cardiovascular diseases (CVDs) have a high mortality rate, and despite the several available therapeutic targets, non-response to antihypertensives remains a common problem. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are important classes of drugs recommended as first-line therapy for several CVDs. However, response to ACEIs and ARBs varies among treated patients. Pharmacogenomics assesses how an individual's genetic characteristics affect their likely response to drug therapy. Currently, numerous studies suggest that genetic polymorphisms may contribute to variability in drug response. Moreover, further studies evaluating gene-gene interactions within signaling pathways in response to antihypertensives might help to unravel potential genetic predictors for antihypertensive response. This review summarizes the pharmacogenetic data for ACEIs and ARBs in patients with CVD, and discusses the potential pharmacogenetics of these classes of antihypertensives in clinical practice. However, replication studies in different populations are needed. In addition, studies that evaluate gene-gene interactions that share signaling pathways in the response to antihypertensive drugs might facilitate the discovery of genetic predictors for antihypertensive response.
Asunto(s)
Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Enfermedades Cardiovasculares , Farmacogenética , Humanos , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/tratamiento farmacológico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , AnimalesRESUMEN
Chronic Chagas cardiomyopathy (CCC) has unique pathogenic and clinical features with worse prognosis than other causes of heart failure (HF), despite the fact that patients with CCC are often younger and have fewer comorbidities. Patients with CCC were not adequately represented in any of the landmark HF studies that support current treatment guidelines. PARACHUTE-HF (Prevention And Reduction of Adverse outcomes in Chagasic Heart failUre Trial Evaluation) is an active-controlled, randomized, phase IV trial designed to evaluate the effect of sacubitril/valsartan 200 mg twice daily vs enalapril 10 mg twice daily added to standard of care treatment for HF. The study aims to enroll approximately 900 patients with CCC and reduced ejection fraction at around 100 sites in Latin America. The primary outcome is a hierarchical composite of time from randomization to cardiovascular death, first HF hospitalization, or relative change from baseline to week 12 in NT-proBNP levels. PARACHUTE-HF will provide new data on the treatment of this high-risk population. (Efficacy and Safety of Sacubitril/Valsartan Compared With Enalapril on Morbidity, Mortality, and NT-proBNP Change in Patients With CCC [PARACHUTE-HF]; NCT04023227).
Asunto(s)
Aminobutiratos , Antagonistas de Receptores de Angiotensina , Compuestos de Bifenilo , Cardiomiopatía Chagásica , Combinación de Medicamentos , Enalapril , Insuficiencia Cardíaca , Tetrazoles , Valsartán , Humanos , Compuestos de Bifenilo/uso terapéutico , Aminobutiratos/uso terapéutico , Enalapril/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Cardiomiopatía Chagásica/tratamiento farmacológico , Insuficiencia Cardíaca/tratamiento farmacológico , Tetrazoles/uso terapéutico , Volumen Sistólico/fisiología , Fragmentos de Péptidos/sangre , Enfermedad Crónica , Péptido Natriurético Encefálico/sangre , Masculino , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Femenino , Resultado del TratamientoRESUMEN
The Jatropha curcas cake, a protein-rich by-product of biofuel production, was the subject of our study. We identified and quantified the ACE inhibitory, antioxidant, and antidiabetic activities of bioactive peptides from a Jatropha curcas L. var Sevangel protein isolate. The protein isolate (20.44% recovered dry matter, 38.75% protein content, and 34.98% protein yield) was subjected to two enzyme systems for hydrolysis: alcalase (PEJA) and flavourzyme (PEJF), recording every 2 h until 8 h had passed. The highest proteolytic capacity in PEJA was reached at 2 h (4041.38 ± 50.89), while in PEJF, it was reached at 6 h (3435.16 ± 59.31). Gel electrophoresis of the PEJA and PEJF samples showed bands corresponding to peptides smaller than 10 kDa in both systems studied. The highest values for the antioxidant capacity (DPPH) were obtained at 4 h for PEJA (56.17 ± 1.14), while they were obtained at 6 h for PEJF (26.64 ± 0.52). The highest values for the antihypertensive capacity were recorded at 6 h (86.46 ± 1.85) in PEJF. The highest antidiabetic capacity obtained for PEJA and PEJF was observed at 6 h, 68.86 ± 8.27 and 52.75 ± 2.23, respectively. This is the first report of their antidiabetic activity. Notably, alcalase hydrolysate outperformed flavourzyme hydrolysate and the cereals reported in other studies, confirming its better multi-bioactivity.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina , Antioxidantes , Hipoglucemiantes , Jatropha , Proteínas de Plantas , Jatropha/química , Hidrólisis , Antioxidantes/química , Antioxidantes/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/química , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Proteínas de Plantas/química , Proteínas de Plantas/aislamiento & purificación , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Subtilisinas/metabolismo , Subtilisinas/química , EndopeptidasasRESUMEN
Although TRPV1 receptors play an essential role in the adverse effects on the airways following captopril treatment, there is no available evidence of their involvement in treatment regimens involving repeated doses of captopril. Comparing the difference in these two treatment regimens is essential since captopril is a continuous-use medication. Thus, this study explored the role of the transient receptor potential vanilloid 1 (TRPV1) in the effects of captopril on rat airways using two treatment regimens. Airway resistance, bronchoalveolar lavage (BAL), and histological and immunohistochemical analyses were conducted in rats administered with single or repeated doses of captopril. This study showed that the hyperresponsiveness to bradykinin and capsaicin in captopril-treated rats was acute. Treatment with the selective B2 antagonist, HOE140 reduced bradykinin hyperresponsiveness and abolished capsaicin exacerbation in single-dose captopril-treated rats. Likewise, degeneration of TRPV1-positive neurones also reduced hyperresponsiveness to bradykinin. Single-dose captopril treatment increased leukocyte infiltration in the BAL when compared with the vehicle and this increase was reduced by TRPV1-positive neurone degeneration. However, when compared with the vehicle treatment, animals treated with repeated doses of captopril showed an increase in leukocyte influx as early as 1 h after the last captopril treatment, but this effect disappeared after 24 h. Additionally, an increase in TRPV1 expression occurred only in animals who received repeated captopril doses and the degeneration of TRPV1-positive neurones attenuated TRPV1 upregulation. In conclusion, these data strongly indicate that a treatment regimen involving multiple doses of captopril not only enhances sensitisation but also upregulates TRPV1 expression. Consequently, targeting TRPV1 could serve as a promising strategy to reduce the negative impact of captopril on the airways.
Asunto(s)
Bradiquinina , Líquido del Lavado Bronquioalveolar , Capsaicina , Captopril , Canales Catiónicos TRPV , Animales , Captopril/farmacología , Canales Catiónicos TRPV/metabolismo , Ratas , Masculino , Bradiquinina/farmacología , Capsaicina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Ratas Sprague-Dawley , Resistencia de las Vías Respiratorias/efectos de los fármacos , Antagonistas del Receptor de Bradiquinina B2/farmacología , Relación Dosis-Respuesta a Droga , Hiperreactividad Bronquial/inducido químicamente , Hiperreactividad Bronquial/tratamiento farmacológico , Neuronas/efectos de los fármacos , Neuronas/metabolismoRESUMEN
The renin-angiotensin system (RAS)-a classical blood pressure regulator-largely contributes to healthy organ development and function. Besides, RAS activation promotes age-related changes and age-associated diseases, which are attenuated/abolished by RAS-blockade in several mammalian species. RAS-blockers also increase rodent lifespan. In previous work, we discussed how RAS-blockade downregulates mTOR and growth hormone/IGF-1 signaling, and stimulates AMPK activity (together with klotho, sirtuin, and vitamin D-receptor upregulation), and proposed that at least some of RAS-blockade's aging benefits are mediated through regulation of these intermediaries and their signaling to mitochondria. Here, we included RAS-blockade's impact on other aging regulatory pathways, that is, TGF-ß, NF-kB, PI3K, MAPK, PKC, Notch, and Wnt, all of which affect mitochondria. No direct evidence is available on RAS/RAS-blockade-aging regulatory pathway-mitochondria interactions. However, existing results allow to conjecture that RAS-blockers neutralize mitochondrial dysfunction by acting on the discussed pathways. The reviewed evidence led us to propose that the foundation is laid for conducting clinical trials aimed at testing whether angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB)-even at subclinical doses-offer the possibility to live longer and in better health. As ACEi and ARB are low cost and well-tolerated anti-hypertension therapies in use for over 35 years, investigating their administration to attenuate/prevent aging effects seems simple to implement.
Asunto(s)
Envejecimiento , Inhibidores de la Enzima Convertidora de Angiotensina , Sistema Renina-Angiotensina , Humanos , Sistema Renina-Angiotensina/efectos de los fármacos , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Envejecimiento/fisiología , Animales , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Transducción de Señal/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Antagonistas de Receptores de Angiotensina/farmacología , Antagonistas de Receptores de Angiotensina/uso terapéuticoRESUMEN
Anticipating a global increase in cardiovascular diseases, there is an expected surge in the use of angiotensin-converting enzyme inhibitors, notably captopril (CAP). This heightened usage raises significant environmental apprehensions, mainly due to limited knowledge regarding CAP's toxic effects on aquatic species. In response to these concerns, the current study aimed to tackle this knowledge gap by evaluating the potential influence of nominal concentrations of CAP (0.2-2000 µg/L) on the embryonic development of Danio rerio. The findings revealed that CAP at all concentrations, even at concentrations considered environmentally significant (0.2 and 2 µg/L), induced various malformations in the embryos, ultimately leading to their mortality. Main malformations included pericardial edema, craniofacial malformation, scoliosis, tail deformation, and yolk sac deformation. In addition, CAP significantly altered the antioxidant activity of superoxide dismutase and catalase across all concentrations. Simultaneously, it elevated lipid peroxidation levels, hydroperoxides, and carbonylic proteins in the embryos, eliciting a substantial oxidative stress response. Likewise, CAP, at all concentrations, exerted significant modulatory effects on the expression of genes associated with apoptosis (bax, bcl2, p53, and casp3), organogenesis (tbx2a, tbx2b, and irx3b), and ion exchange (slc12a1 and kcnj1) in Danio rerio embryos. Both augmentation and reduction in the expression levels of these genes characterized this modulation. The Pearson correlation analysis indicated a close association between oxidative damage biomarkers and the expression patterns of all examined genes with the elevated incidence of malformations and mortality in the embryos. In summary, it can be deduced that CAP poses a threat to aquatic species. Nevertheless, further research is imperative to enhance our understanding of the environmental implications of this pharmaceutical compound.
Asunto(s)
Captopril , Embrión no Mamífero , Desarrollo Embrionario , Contaminantes Químicos del Agua , Pez Cebra , Animales , Contaminantes Químicos del Agua/toxicidad , Desarrollo Embrionario/efectos de los fármacos , Captopril/toxicidad , Embrión no Mamífero/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Inhibidores de la Enzima Convertidora de Angiotensina/toxicidadRESUMEN
Obesity over-activates the classical arm of the renin-angiotensin system (RAS), impairing skeletal muscle remodeling. We aimed to compare the effect of exercise training and enalapril, an angiotensin-converting enzyme inhibitor, on RAS modulation in the skeletal muscle of obese animals. Thus, we divided C57BL/6 mice into two groups: standard chow (SC) and high-fat (HF) diet for 16 weeks. At the eighth week, the HF-fed animals were divided into four subgroups-sedentary (HF), treated with enalapril (HF-E), exercise training protocol (HF-T), and combined interventions (HF-ET). After 8 weeks of treatment, we evaluated body mass and index (BMI), body composition, exercise capacity, muscle morphology, and skeletal muscle molecular markers. All interventions resulted in lower BMI and attenuation of overactivation in the classical arm, while favoring the B2R in the bradykinin receptors profile. This was associated with reduced apoptosis markers in obese skeletal muscles. The HF-T group showed an increase in muscle mass and expression of biosynthesis markers and a reduction in expression of degradation markers and muscle fiber atrophy due to obesity. These findings suggest that the combination intervention did not have a synergistic effect against obesity-induced muscle remodeling. Additionally, the use of enalapril impaired muscle's physiological adaptations to exercise training.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina , Enalapril , Ratones Endogámicos C57BL , Músculo Esquelético , Obesidad , Condicionamiento Físico Animal , Animales , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Obesidad/metabolismo , Obesidad/fisiopatología , Condicionamiento Físico Animal/fisiología , Ratones , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Enalapril/farmacología , Dieta Alta en Grasa/efectos adversos , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/fisiologíaRESUMEN
Diabetic retinopathy (DR) is a complication of diabetes with a complex pathophysiology and multiple factors involved. Recently, it has been found that the upregulation of the renin-angiotensin-aldosterone system (RAAS) leads to overexpression of angiotensin II (Ang II), which induces oxidative stress, inflammation, and angiogenesis in the retina. Therefore, RAAS may be a promising therapeutic target in DR. Notably, RAAS inhibitors are often used in the treatment of hypertension. Still, the potential role and mechanism of DR must be further studied. In this review, we discuss and summarize the pathology and potential therapeutic goals of RAAS in DR.
Asunto(s)
Retinopatía Diabética , Sistema Renina-Angiotensina , Humanos , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/fisiopatología , Sistema Renina-Angiotensina/fisiología , Sistema Renina-Angiotensina/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Angiotensina II/fisiología , AnimalesRESUMEN
Since ancient times, the consumption of fermented low-alcoholic beverages has enjoyed widespread popularity in various countries, because of their distinct flavors and health benefits. Several studies have demonstrated that light to moderate alcohol consumption is associated with beneficial effects on human health, mainly in cardiovascular disease prevention. Fermented beverages have different non-ethanol components that confer beneficial health effects. These bioactive compounds are mainly peptides that have often been overlooked or poorly explored in numerous fermented beverages. The aim of this review is to provide knowledge and generate interest in the biological activities of peptides that are present and/or released during the fermentation process of widely consumed traditional fermented beverages. Additionally, a brief description of the microorganisms involved in these beverages is provided. Furthermore, this review also explores topics related to the detection, isolation, and identification of peptides, addressing the structure-activity relationships of both antioxidant and angiotensin-converting enzyme inhibitory (ACE-I) activities.
Asunto(s)
Fermentación , Péptidos , Péptidos/farmacología , Humanos , Antioxidantes , Bebidas , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Alimentos FermentadosRESUMEN
The impact of different pressure levels in the HHP-assisted hydrolysis by Alcalase of quinoa proteins on the catalytic efficiency, peptide release, phenolic compounds content, and biological activities was investigated. The protein profile (SDS-PAGE) showed a more extensive peptide breakdown for the HHP-assisted proteolysis at 300-400 MPa, which was confirmed by the higher extent of hydrolysis and peptide concentration. Quinoa protein hydrolysates (QPH) produced at 200 and 300 MPa exhibited higher total phenolic contents and antioxidant activities (methanol-acetone and aqueous extracts) when compared to the non-hydrolyzed (QPI) and non-pressurized hydrolyzed samples. Kaempferol dirhamnosyl-galactopyranoside was the prevalent phenolic compound in those samples, increasing total flavonoids by 1.8-fold over QPI. The QPH produced at 300 MPa inhibited ACE more effectively, exhibiting the greatest anti-hypertensive potential, along with the presence of several ACE-inhibitory peptides. The peptide sequences GSHWPFGGK, FSIAWPR, and PWLNFK presented the highest Peptide Ranker scores and were predicted to have ACE inhibitory, DPP-IV inhibitory, and antioxidant activities. Mild pressure levels were effective in producing QPH with enhanced functionality due to the effects of bioactive soluble phenolics and low molecular weight peptides.
Asunto(s)
Antioxidantes , Chenopodium quinoa , Hidrólisis , Antioxidantes/farmacología , Antioxidantes/química , Hidrolisados de Proteína/química , Inhibidores de la Enzima Convertidora de Angiotensina/química , Péptidos/químicaRESUMEN
Hypertension is a major risk factor for cardiovascular disease and the leading cause of death in Colombia. While the rate of hypertension awareness in Colombia is generally high, rates of treatment initiation, adherence, and blood pressure (BP) control are suboptimal. Major international hypertension guidelines recommend starting treatment with a combination of antihypertensive agents, and the use of a single-pill combination (SPC) to maximize adherence. In contrast, Colombian hypertension guidelines recommend starting treatment with diuretic monotherapy in most patients, and only initiating combination therapy in those with BP > 160/100 mmHg. Therefore, the aim of the current narrative review is to examine the rationale for using SPCs to treat hypertension in Colombia, in the context of the major issues for BP control there. There is evidence of widespread therapeutic inertia in hypertension management, particularly in primary care, in Colombia. Moreover, combination therapy, angiotensin-converting enzyme inhibitors, and long-acting calcium channel blockers, which are internationally recommended as first-line drug therapies, are underutilized there. Adherence to antihypertensive therapy is low in Colombia and may be enhanced by use of SPCs as well as better patient education and follow-up. While there are promising national initiatives to improve BP management, more needs to be done by individual physicians. Antihypertensive SPCs are available on the national essential medicines list and may help to overcome some of the problems with suboptimal adherence, therapeutic inertia, and low rates of BP control that contribute to the high cardiovascular death rate in Colombia.
Asunto(s)
Antihipertensivos , Hipertensión , Humanos , Antihipertensivos/uso terapéutico , Colombia , Hipertensión/tratamiento farmacológico , Bloqueadores de los Canales de Calcio , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Presión Sanguínea , Quimioterapia Combinada , Combinación de MedicamentosRESUMEN
BACKGROUND: Systemic hypertension (SH) is the main risk factor to cognitive deterioration, whereas visuospatial memory is more vulnerable to ageing. Some antihypertensive agents have a neuroprotector effect, however, such effects could be masked by comorbidities and/or the lack of effective control on the arterial pressure of patients. OBJECTIVE: To assess this, the evaluation of incidental visuospatial memory of SH patients and the relation to the treatment received and the effective control of pressure were made. METHOD: 80 patients (46 woman) were included grouped by the received medication: angiotensin 2 receptor blockers (ARB) or angiotensin converting enzyme inhibitors (ACEI). A multiple correlation analysis between visuospatial scores and clinical variables was made; also, a mixed model analysis (fixed factors: treatment, pressure control, diabetes comorbidity; aleatory factors: age, schooling, months from SH diagnoses). RESULTS: Half of the patients had a controlled pressure, from them the higher proportion received ARB, and a minor number of patients received ACEI. The normotensive patients receiving ACEI were inefficient whereas the hypertensive patients were more efficient. The systolic pressure was negatively related with the visuospatial scores in spite of no correlations occurred with MoCA and Raven tests. CONCLUSIONS: The visuospatial incidental/intentional scores were negatively correlated with systolic pressure. The efficiency in the visuospatial ability depends on the interaction of treatment and effective control of blood pressure. The interaction between treatment and effective pressure control must be taken in count when cognitive deterioration is studied.
ANTECEDENTES: La hipertensión arterial sistémica (HAS) es el principal factor de riesgo para el deterioro cognitivo; por otro lado, la memoria visuoespacial es más vulnerable al envejecimiento. Algunos fármacos antihipertensivos tienen un efecto neuroprotector, pero tal efecto puede enmascararse o bien no manifestarse por comorbilidad o por falta de control efectivo de la presión arterial. OBJETIVO: Evaluar las alteraciones en la memoria visuoespacial incidental de pacientes con HAS en relación con su tratamiento antihipertensivo y su control de la presión. MÉTODO: Se incluyeron 80 pacientes con HAS (46 mujeres), agrupados por su medicación en bloqueadores de los receptores de la angiotensina II (BRA) o inhibidores de la enzima convertidora de angiotensina (IECA). Se realizó un análisis de correlaciones múltiples para los puntajes obtenidos en la prueba de memoria visuoespacial incidental/intencional y un análisis de modelos mixtos (factores fijos: tratamiento, control de la presión y comorbilidad con diabetes; factores aleatorios: edad, escolaridad, meses desde el diagnóstico de HAS y coeficiente intelectual). RESULTADOS: De los pacientes controlados, la mayoría de los que recibían BRA fueron eficientes y los que recibían IECA fueron deficientes. De los que recibían IECA, los descontrolados hipertensos fueron más eficientes que los normotensos. La memoria visuoespacial se correlacionó negativamente con la presión sistólica a pesar de no haber diferencias en MoCA y Raven. CONCLUSIONES: La eficiencia en la memoria visuoespacial dependió de la interacción del tratamiento y el control de la presión. Ambos factores, tratamiento y control efectivo de la presión, deben considerarse en la evaluación del deterioro cognitivo asociado a la HAS.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina , Hipertensión , Femenino , Humanos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Antagonistas de Receptores de Angiotensina/uso terapéutico , Antagonistas de Receptores de Angiotensina/farmacología , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Antihipertensivos/uso terapéutico , Presión SanguíneaRESUMEN
OBJECTIVE: Enalapril has shown satisfactory potential in controlling increased and sustained blood pressure (BP). However, multiple dysregulated mechanisms that interact with each other and are involved in the pathophysiology of arterial hypertension may not be affected, contributing to the remaining cardiovascular risk. Using an exercise training protocol, we investigated whether adding both approaches to arterial hypertension management could promote higher modulation of regulatory mechanisms of BP in postmenopausal rats. METHODS: Spontaneously hypertensive rats were allocated into sedentary (S) and ovariectomized groups: sedentary (OS), sedentary treated with enalapril maleate (OSE) and trained treated with enalapril maleate (OTE). Both the pharmacological and exercise training protocols lasted for 8âweeks. The BP was directly recorded. Inflammation and oxidative stress were evaluated in the cardiac tissue. RESULTS: Although BP reduction was similar between OSE and OTE, trained group showed lower vasopressor systems outflow after sympathetic ganglion blocking by hexamethonium (mean BP) (OTE: -53.7â±â9.86 vs. OS: -75.7â±â19.2âmmHg). Bradycardic and tachycardic response were increased in OTE group (-1.4â±â0.4 and -2.6â±â0.4 vs. OS: -0.6â±â0.3 and -1.3â±â0.4âbpm/mmHg, respectively), as well as BP variability. In addition, the combination of approaches induced an increase in interleukin 10, antioxidant defense (catalase and glutathione peroxidase) and nitrite levels compared with the OS group. CONCLUSION: Despite similar BP, the inclusion of exercise training in antihypertensive drug treatment exacerbates the positive adaptations induced by enalapril alone on autonomic, inflammatory and oxidative stress profiles, probably affecting end-organ damage and remaining risk.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina , Hipertensión , Ratas , Animales , Presión Sanguínea , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Enalapril/farmacología , Ratas Endogámicas SHRRESUMEN
INTRODUCTION: Although several guidelines recommend that patients with heart failure with reduced ejection fraction (HFrEF) be treated with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEIs/ARBs) or angiotensin receptor-neprilysin inhibitors (ARNIs), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 inhibitor (SGLT2i), there are still several gaps in their prescription and dosage in Colombia. This study aimed to describe the use patterns of HFrEF treatments in the Colombian Heart Failure Registry (RECOLFACA). METHODS: Patients with HFrEF enrolled in RECOLFACA during 2017-2019 were included. Heart failure (HF) medication prescription and daily dose were assessed using absolute numbers and proportions. Therapeutic schemes of patients treated by internal medicine specialists were compared with those treated by cardiologists. RESULTS: Out of 2,528 patients in the registry, 1,384 (54.7%) had HFrEF. Among those individuals, 88.9% were prescribed beta-blockers, 72.3% with ACEI/ARBs, 67.9% with MRAs, and 13.1% with ARNIs. Moreover, less than a third of the total patients reached the target doses recommended by the European HF guidelines. No significant differences in the therapeutic schemes or target doses were observed between patients treated by internal medicine specialists or cardiologists. CONCLUSION: Prescription rates and target dose achievement are suboptimal in Colombia. Nevertheless, RECOLFACA had one of the highest prescription rates of beta-blockers and MRAs compared to some of the most recent HF registries. However, ARNIs remain underprescribed. Continuous registry updates can improve the identification of patients suitable for ARNI and SGLT2i therapy to promote their use in clinical practice.
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Antagonistas Adrenérgicos beta , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Adhesión a Directriz , Insuficiencia Cardíaca , Sistema de Registros , Volumen Sistólico , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Masculino , Femenino , Colombia , Adhesión a Directriz/estadística & datos numéricos , Anciano , Persona de Mediana Edad , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antagonistas Adrenérgicos beta/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Guías de Práctica Clínica como Asunto , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéuticoRESUMEN
Overactivation of the classic arm of the renin-angiotensin system (RAS) is one of the main mechanisms involved in obesity-related cardiac remodeling, and a possible relationship between RAS and ER stress in the cardiovascular system have been described. Thus, the aim of this study is to evaluate if activating the protective arm of the RAS by ACE inhibition or aerobic exercise training could overturn diet-induced pathological cardiac hypertrophy by attenuating ER stress. Male C57BL/6 mice were fed a control (SC) or a high-fat diet (HF) for 16 weeks. In the 8th week, HF-fed animals were randomly divided into HF, enalapril treatment (HF-En), and aerobic exercise training (HF-Ex) groups. Body mass (BM), food and energy intake, plasma analyzes, systolic blood pressure (SBP), physical conditioning, and plasma ACE and ACE2 activity were evaluated. Cardiac morphology, and protein expression of hypertrophy, cardiac metabolism, RAS, and ER stress markers were assessed. Data presented as mean ± standard deviation and analyzed by one-way ANOVA with Holm-Sidak post-hoc. HF group had increased BM and SBP, and developed pathological concentric cardiac hypertrophy, with overactivation of the classic arm of the RAS, and higher ER stress. Both interventions reverted the increase in BM, and SBP, and favored the protective arm of the RAS. Enalapril treatment improved pathological cardiac hypertrophy with partial reversal of the concentric pattern, and slightly attenuated cardiac ER stress. In contrast, aerobic exercise training induced physiological eccentric cardiac hypertrophy, and fully diminished ER stress.
Asunto(s)
Cardiomegalia , Enalapril , Estrés del Retículo Endoplásmico , Obesidad , Condicionamiento Físico Animal , Animales , Masculino , Enzima Convertidora de Angiotensina 2/sangre , Cardiomegalia/etiología , Cardiomegalia/terapia , Enalapril/farmacología , Enalapril/uso terapéutico , Estrés del Retículo Endoplásmico/efectos de los fármacos , Regulación de la Expresión Génica/fisiología , Ratones Endogámicos C57BL , Obesidad/complicaciones , Peptidil-Dipeptidasa A/sangre , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/fisiología , Transducción de Señal/fisiología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéuticoRESUMEN
This study presents a systematic review of the scientific and technological production related to the use of systems based on UV, H2O2, and Cl2 for the elimination of antibiotic-resistant bacteria (ARB) and genes associated with antibiotic resistance (ARGs). Using the Pro Know-C (Knowledge Development Process-Constructivist) methodology, a portfolio was created and analyzed that includes 19 articles and 18 patents published between 2011 and 2022. The results show a greater scientific-technological production in UV irradiation systems (8 articles and 5 patents) and the binary combination UV/H2O2 (9 articles and 4 patents). It was emphasized that UV irradiation alone focuses mainly on the removal of ARB, while the addition of H2O2 or Cl2, either individually or in binary combinations with UV, enhances the removal of ARB and ARG. The need for further research on the UV/H2O2/Cl2 system is emphasized, as gaps in the scientific-technological production of this system (0 articles and 2 patents), especially in its electrochemically assisted implementation, have been identified. Despite the gaps identified, there are promising prospects for the use of combined electrochemically assisted UV/H2O2/Cl2 disinfection systems. This is demonstrated by the effective removal of a wide range of contaminants, including ARB, fungi, and viruses, as well as microorganisms resistant to conventional disinfectants, while reducing the formation of toxic by-products.
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Peróxido de Hidrógeno , Purificación del Agua , Antagonistas de Receptores de Angiotensina , Purificación del Agua/métodos , Cloro , Inhibidores de la Enzima Convertidora de Angiotensina , Farmacorresistencia Microbiana/genética , Bacterias/genética , Desinfección/métodos , Rayos UltravioletaRESUMEN
An acidic beverage was formulated with xanthan gum (XG), pectin (P) and brewer spent grain (BSG) peptides with antioxidant and antihypertensive properties. The impact of hydrocolloids levels on peptide bioaccessibility was studied. Peptides were obtained from BSG using Purazyme and Flavourzyme enzymes. BSG peptides were fractionated by ultrafiltration (UF) and four fractions were obtained: F1 (>10 kDa), F2 (10-5 kDa), F3 (1-5 kDa), and F4 (<1 kDa). F3 showed the highest protein purity, ferulic acid content, proportion of amphipathic peptides, and bioactive properties (ABTS+ radical scavenging and ACE-I inhibitory activity). The identified peptides from F3 by tandem mass spectrometry were 138. In silico analysis showed that 26 identified peptides had ABTS+ inhibitory activity, while 59 ones presented good antihypertensive properties. The effect of XG and P levels on bioaccessibility of F3 peptides in the formulated beverages was studied by a central composite experimental design. It was observed that F3 peptides interacted with hydrocolloids by electrostatic forces at pH of formulated beverages. The addition of hydrocolloids to formulation modulated the release of the antioxidant peptides and protected the degradation of ACE-I inhibitory peptides from F3 during simulated gastrointestinal digestion. Finally, the level of hydrocolloids that produced intermediate viscosities in the formulated beverages improved the bioaccessibility of the F3 peptides.
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Antihipertensivos , Antioxidantes , Benzotiazoles , Polisacáridos Bacterianos , Ácidos Sulfónicos , Antihipertensivos/química , Antioxidantes/análisis , Hidrólisis , Inhibidores de la Enzima Convertidora de Angiotensina/química , Pectinas/análisis , Hidrolisados de Proteína/química , Péptidos/química , Grano Comestible/química , Coloides/análisisRESUMEN
BACKGROUND: About 80% of cardiovascular diseases (including heart failure [HF]) occur in low-income and developing countries. However, most clinical trials are conducted in developed countries. HYPOTHESIS: The American Registry of Ambulatory or Acutely Decompensated Heart Failure (AMERICCAASS) aims to describe the sociodemographic characteristics of HF, comorbidities, clinical presentation, and pharmacological management of patients with ambulatory or acutely decompensated HF in America. METHODOLOGY: Descriptive, observational, prospective, and multicenter registry, which includes patients >18 years with HF in an outpatient or hospital setting. Collected information is stored in the REDCap electronic platform. Quantitative variables are defined according to the normality of the variable using the Shapiro-Wilk test. RESULTS: This analysis includes data from the first 1000 patients recruited. 63.5% were men, the median age of 66 years (interquartile range 56.7-75.4), and 77.6% of the patients were older than 55 years old. The percentage of use of the four pharmacological pillars at the time of recruitment was 70.7% for beta-blockers (BB), 77.4% for angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB II)/angiotensin receptor-neprilysin inhibitor (ARNI), 56.8% for mineralocorticoid receptor antagonists (MRA), and 30.7% for sodium-glucose cotransporter type-2 inhibitors (SGLT2i). The main cause of decompensation in hospitalized patients was HF progression (64.4%), and the predominant hemodynamic profile was wet-warm (68.3%). CONCLUSIONS: AMERICCAASS is the first continental registry to include hospitalized or outpatient patients with HF. Regarding optimal medical therapy, approximately a quarter of the patients still need to receive BB and ACEI/ARB/ARNI, less than half do not receive MRA, and more than two-thirds do not receive SGLT2i.
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Inhibidores de la Enzima Convertidora de Angiotensina , Insuficiencia Cardíaca , Masculino , Humanos , Estados Unidos/epidemiología , Anciano , Persona de Mediana Edad , Femenino , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Estudios Prospectivos , Volumen Sistólico , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/epidemiología , Sistema de Registros , Antagonistas Adrenérgicos beta/uso terapéutico , Antagonistas de Receptores de Mineralocorticoides/uso terapéuticoRESUMEN
OBJECTIVES: COVID-19, caused by SARS-CoV-2, has spread around the world since 2019. In severe cases, COVID-19 can lead to hospitalization and death. Systemic arterial hypertension and other comorbidities are associated with serious COVID-19 infection. Literature is unclear whether antihypertensive therapy with angiotensin receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors affect COVID-19 outcomes. We aim to assess whether ACEI/ARB therapy is a risk factor for worse respiratory outcomes related to COVID-19 in hospitalized patients. METHODS: Retrospective study enrolling admitted COVID-19-diagnosed patients by RT-PCR at the Hospital Geral de Fortaleza, Brazil, during 2021. Patient medical records, sociodemographic, and clinical data were analyzed. Chest CT images were analyzed using CAD4COVID-CT/Thirona™ software. RESULTS: A total of 294 patients took part in the study. A cut-off point of 66% of pulmonary involvement was found by ROC curve, with patients having higher risk of death and intubation and lower 60-day survival. Advanced age (RR 1.025, P=0.001) and intubation (RR 16.747, P<0.001) were significantly associated with a higher risk of death. Advanced age (RR 1.023, P=0.001) and the use of noninvasive ventilation (RR 1.548, P=0.037) were associated with a higher risk of intubation. Lung involvement (>66%) increased the risk of death by almost 2.5-fold (RR 2.439, P<0.001) and by more than 2.3-fold the risk of intubation (RR 2.317, P<0.001). CONCLUSIONS: Altogether, our findings suggest that ACEI or ARB therapy does not affect the risk of death and disease course during hospitalization.