RESUMO
Cardiovascular diseases (CVD) are the main causes of death in hemodialysis patients, representing a public health challenge. We investigated the effect of different antihypertensive treatments on circulating levels of renin-angiotensin system (RAS) components in end-stage renal disease (ESRD) patients on hemodialysis. ESRD patients were grouped following the prescribed antihypertensive drugs: ß-blocker, ß-blocker+ACEi and ß-blocker+AT1R blocker. ESDR patients under no antihypertensive drug treatment were used as controls. Blood samples were collected before hemodialysis sessions. Enzymatic activities of the angiotensin-converting enzymes ACE and ACE2 were measured through fluorescence assays and plasma concentrations of the peptides Angiotensin II (Ang II) and Angiotensin-(1-7) [Ang-(1-7)] were quantified using mass spectrometry (LC-MS/MS). ACE activity was decreased only in the ß-blocker+ACEi group compared to the ß-blocker+AT1R, while ACE2 activity did not change according to the antihypertensive treatment. Both Ang II and Ang-(1-7) levels also did not change according to the antihypertensive treatment. We concluded that the treatment of ESRD patients on hemodialysis with different antihypertensive drugs do not alter the circulating levels of RAS components.
Assuntos
Anti-Hipertensivos , Falência Renal Crônica , Humanos , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Enzima de Conversão de Angiotensina 2/farmacologia , Cromatografia Líquida , Espectrometria de Massas em Tandem , Sistema Renina-Angiotensina , Peptidil Dipeptidase A/metabolismo , Peptídeos/farmacologia , Falência Renal Crônica/tratamento farmacológico , Angiotensina II/farmacologia , Fragmentos de Peptídeos/metabolismo , Diálise RenalRESUMO
Arterial stiffness, frequently associated with hypertension, is associated with disorganization of the vascular wall and has been recognized as an independent predictor of all-cause mortality. The identification of the molecular mechanisms involved in aortic stiffness would be an emerging target for hypertension therapeutic intervention. This study evaluated the effects of perindopril on pulse wave velocity (PWV) and on the differentially expressed proteins in aorta of spontaneously hypertensive rats (SHR), using a proteomic approach. SHR and Wistar rats were treated with perindopril (SHRP) or water (SHRc and Wistar rats) for 8 weeks. At the end, SHRC presented higher systolic blood pressure (SBP, +70%) and PWV (+31%) compared with Wistar rats. SHRP had higher values of nitrite concentration and lower PWV compared with SHRC. From 21 upregulated proteins in the aortic wall from SHRC, most of them were involved with the actin cytoskeleton organization, like Tropomyosin and Cofilin-1. After perindopril treatment, there was an upregulation of the GDP dissociation inhibitors (GDIs), which normally inhibits the RhoA/Rho-kinase/cofilin-1 pathway and may contribute to decreased arterial stiffening. In conclusion, the results of the present study revealed that treatment with perindopril reduced SBP and PWV in SHR. In addition, the proteomic analysis in aorta suggested, for the first time, that the RhoA/Rho-kinase/Cofilin-1 pathway may be inhibited by perindopril-induced upregulation of GDIs or increases in NO bioavailability in SHR. Therefore, we may propose that activation of GDIs or inhibition of RhoA/Rho-kinase pathway could be a possible strategy to treat arterial stiffness.
RESUMO
In this study, we characterized three novel peptides derived from the 19 kDa α-zein, and determined their bioactive profile in vitro and developed a structural model in silico. The peptides, 19ZP1, 19ZP2 and 19ZP3, formed α-helical structures and had positive and negative electrostatic potential surfaces (range of -1 to +1). According to the in silico algorithms, the peptides displayed low probabilities for cytotoxicity (≤0.05%), cell penetration (10-33%) and antioxidant activities (9-12.5%). Instead, they displayed a 40% probability for angiotensin-converting enzyme (ACE) inhibitory activity. For in vitro characterization, peptides were synthesized by solid phase synthesis and tested accordingly. We assumed α-helical structures for 19ZP1 and 19ZP2 under hydrophobic conditions. The peptides displayed antioxidant activity and ACE-inhibitory activity, with 19ZP1 being the most active. Our results highlight that the 19 kDa α-zein sequences could be explored as a source of bioactive peptides, and indicate that in silico approaches are useful to predict peptide bioactivities, but more structural analysis is necessary to obtain more accurate data.
Assuntos
Simulação por Computador , Peptídeos/análise , Peptídeos/farmacologia , Zea mays/química , Zeína/química , Sequência de Aminoácidos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Antioxidantes/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Endocitose/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Peptídeos/síntese química , Peptídeos/química , Solventes/químicaRESUMO
Angiotensin-(1-7) [Ang-(1-7)], a counter-regulatory peptide of the renin-angiotensin system (RAS) exerts its effects through the G-protein-coupled receptor Mas, which is expressed in different tissues, including the brain. Ang-(1-7) has a broad range of effects beyond the well-described cardiovascular and renal actions, including the modulation of emotional and behavioural responses. In the present study we tested the hypothesis that Ang-(1-7) could attenuate the anxiety- and depression-like behaviours observed in transgenic hypertensive (mRen2)27 rats (TGRs). We also hypothesized that Ang-(1-7) could be involved in the anxiolytic-like effect induced by ACE (angiotensin-converting enzyme) treatment in these hypertensive rats. Therefore, TGRs and Sprague-Dawley rats were subjected to the Elevated Plus Maze (EPM) test, Forced Swimming Test (FST) and Novelty Suppressed Feeding (NSF). TGRs presented a decreased percentage of entries in the open arms of the EPM test, a phenotype reversed by systemic treatment with enalapril or intracerebroventricular infusion of Ang-(1-7). It is interesting that pre-treatment with A779, a selective Mas receptor antagonist, prevented the anxiolytic-like effect induced by the ACE inhibitor. In the NSF test, TGRs showed increased latency to eating, an indicative of a higher aversion in response to a new environment. These animals also showed increased immobility in the FST. Again, Ang-(1-7) reversed this phenotype. Thus, our data showed that Ang-(1-7) can modulate anxiety- and depression-like behaviours in TGRs and warrant further investigation as a new therapy for certain psychiatric disorders.
Assuntos
Angiotensina I/farmacologia , Ansiolíticos/farmacologia , Antidepressivos/farmacologia , Hipertensão/tratamento farmacológico , Fragmentos de Peptídeos/farmacologia , Animais , Enalapril/farmacologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Ratos Transgênicos , Renina/genética , NataçãoRESUMO
SCLERODERMA: renal crisis (SRC), a somewhat rare but serious complication of systemic scleroderma, is one of only a few known rheumatologic emergencies; it presents in as many as 10% of patients with scleroderma. Before the use of angiotensin converting enzyme (ACE) inhibitors to treat SRC, the mortality rate for SRC was extremely high-as much as 90% after 1 year. However, the mortality rate has significantly improved with the early and aggressive use of ACE inhibitors. SRC typically includes acute renal failure and accelerated hypertension. Patients may report headache, changes in vision, fever, dyspnea, and encephalopathy. Laboratory study results can show elevated creatinine levels, thrombocytopenia, and microangiopathic hemolytic anemia (MAHA) with schistocytes on blood smear. Given this clinical and laboratory presentation, SRC can easily be mistaken for TTP in clinical practice, as we demonstrate in 2 presentations of similar cases of SRC, the first in a 36-year-old Caucasian woman and the second in a 54-year-old Caucasian woman. In both cases, SRC masqueraded as TTP, and both patients were almost mistakenly treated for TTP until the clinical picture changed and certain laboratory test and kidney biopsy results confirmed otherwise.
Assuntos
Hipertensão Renal/diagnóstico , Púrpura Trombocitopênica Trombótica/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Hipertensão Renal/fisiopatologia , Pessoa de Meia-Idade , Púrpura Trombocitopênica Trombótica/fisiopatologiaRESUMO
BACKGROUND AND OBJECTIVES: The importance of minimizing the exaggerated sympatho-adrenergic responses and QT interval and QT interval dispersion changes that may develop due to laryngoscopy and tracheal intubation during anesthesia induction in the hypertensive patients is clear. Esmolol decreases the hemodynamic response to laryngoscopy and intubation. However, the effect of esmolol in decreasing the prolonged QT interval and QT interval dispersion as induced by laryngoscopy and intubation is controversial. We investigated the effect of esmolol on the hemodynamic, and corrected-QT interval and corrected-QT interval dispersion changes seen during anesthesia induction in hypertensive patients using angiotensin converting enzyme inhibitors. METHODS: 60 ASA I-II patients, with essential hypertension using angiotensin converting enzyme inhibitors were included in the study. The esmolol group received esmolol at a bolus dose of 500 mcg/kg followed by a 100 mcg/kg/min infusion which continued until the 4th min after intubation. The control group received 0.9% saline similar to the esmolol group. The mean blood pressure, heart rate values and the electrocardiogram records were obtained as baseline values before the anesthesia, 5 min after esmolol and saline administration, 3 min after the induction and 30 s, 2 min and 4 min after intubation. RESULTS: The corrected-QT interval was shorter in the esmolol group (p = 0.012), the corrected-QT interval dispersion interval was longer in the control group (p = 0.034) and the mean heart rate was higher in the control group (p = 0.022) 30 s after intubation. The risk of arrhythmia frequency was higher in the control group in the 4-min period following intubation (p = 0.038). CONCLUSION: Endotracheal intubation was found to prolong corrected-QT interval and corrected-QT interval dispersion, and increase the heart rate during anesthesia induction with propofol in hypertensive patients using angiotensin ...
JUSTIFICATIVA E OBJETIVO: É óbvia a importância de minimizar as respostas simpatoadrenérgicas exageradas e o intervalo QT e a dispersão do intervalo QT que podem ocorrer por causa de laringoscopia e intubação traqueal durante a indução da anestesia em pacientes hipertensos. Esmolol diminui a resposta hemodinâmica à laringoscopia e à intubação. Porém, o efeito de esmolol sobre a redução do intervalo QT prolongado e a dispersão do intervalo QT induzida pela laringoscopia e intubação é controverso. Pesquisamos o efeito de esmolol sobre a hemodinâmica e o intervalo QT corrigido e as alterações da dispersão do intervalo QT observadas durante a indução da anestesia em pacientes hipertensos que receberam inibidores da enzima conversora de angiotensina (IECA). MÉTODOS: Foram incluídos no estudo 60 pacientes, estado físico ASA I-II, com hipertensão arterial essencial e que receberam IECA. O grupo esmolol recebeu uma dose em bolus de 500 mcg kg-1, seguida por infusão contínua de 100 mcg kg-1 min-1 até o quarto minuto após a intubação. O grupo controle recebeu solução salina a 0,9%, semelhantemente ao grupo esmolol. Os valores da pressão arterial média e da frequência cardíaca e os registros do eletrocardiograma foram obtidos durante a fase inicial pré-anestesia, cinco minutos após a administração de esmolol e solução salina, três minutos após a indução e 30 segundos, dois minutos e quatro minutos após a intubação. RESULTADOS: O intervalo QT corrigido foi menor no grupo esmolol (p = 0,012), o intervalo de dispersão do intervalo QT corrigido foi maior no grupo controle (p = 0,034) e a frequência cardíaca média foi maior no grupo controle (p = 0,022) 30 segundos após a intubação. O risco da frequência de arritmia foi maior no grupo controle no quarto minuto após a intubação (p = 0,038). CONCLUSÃO: Descobrimos que a intubação traqueal prolonga o intervalo e a dispersão do intervalo QT corrigido e aumenta a frequência cardíaca durante a indução da ...
JUSTIFICACIÓN Y OBJETIVO: Es evidente la importancia que tiene minimizar las respuestas simpatoadrenérgicas exageradas y el intervalo QT y la dispersión del intervalo QT que pueden ocurrir a causa de la laringoscopia e intubación traqueal durante la inducción de la anestesia en pacientes hipertensos. El esmolol disminuye la respuesta hemodinámica a la laringoscopia y a la intubación. Sin embargo, su efecto sobre la reducción del intervalo QT prolongado y la dispersión del intervalo QT inducida por la laringoscopia e intubación es controvertido. Investigamos el efecto del esmolol sobre la hemodinámica y el intervalo QT corregido, y las alteraciones de la dispersión del intervalo QT observadas durante la inducción de la anestesia en pacientes hipertensos que recibieron inhibidores de la enzima convertidora de la angiotensina. MÉTODOS: Fueron incluidos en el estudio 60 pacientes, estado físico ASA I-II, con hipertensión arterial esencial y que recibieron inhibidores de la enzima convertidora de la angiotensina. El grupo esmolol recibió una dosis en bolos de 500 mcg/kg, seguida de infusión continua de 100 mcg/kg/min hasta el cuarto minuto después de la intubación. El grupo control recibió una solución salina al 0,9%, de forma similar al grupo esmolol. Los valores de la presión arterial media y de la frecuencia cardíaca y los registros del electrocardiograma fueron obtenidos durante la fase inicial preanestésica, 5 min después de la administración del esmolol y la solución salina, 3 min después de la inducción, y 30 s, 2 min y 4 min después de la intubación. RESULTADOS: El intervalo QT corregido fue menor en el grupo esmolol (p = 0,012), el intervalo de dispersión del intervalo QT corregido fue mayor en el grupo control (p = 0,034) y la frecuencia cardíaca media fue mayor en el grupo control (p = 0,022) 30 s después de la intubación. El riesgo de la frecuencia de arritmia fue mayor en el grupo control en el cuarto minuto después de la intubación ...
Assuntos
Humanos , Síndrome do QT Longo/cirurgia , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Antagonistas Adrenérgicos beta/farmacologia , Método Duplo-Cego , Estudos Prospectivos , Hipertensão/fisiopatologia , Intubação Intratraqueal/instrumentação , Laringoscopia/instrumentaçãoRESUMO
BACKGROUND AND OBJECTIVES: The importance of minimizing the exaggerated sympatho-adrenergic responses and QT interval and QT interval dispersion changes that may develop due to laryngoscopy and tracheal intubation during anesthesia induction in the hypertensive patients is clear. Esmolol decreases the hemodynamic response to laryngoscopy and intubation. However, the effect of esmolol in decreasing the prolonged QT interval and QT interval dispersion as induced by laryngoscopy and intubation is controversial. We investigated the effect of esmolol on the hemodynamic, and corrected-QT interval and corrected-QT interval dispersion changes seen during anesthesia induction in hypertensive patients using angiotensin converting enzyme inhibitors. METHODS: 60 ASA I-II patients, with essential hypertension using angiotensin converting enzyme inhibitors were included in the study. The esmolol group received esmolol at a bolus dose of 500mcg/kg followed by a 100mcg/kg/min infusion which continued until the 4th min after intubation. The control group received 0.9% saline similar to the esmolol group. The mean blood pressure, heart rate values and the electrocardiogram records were obtained as baseline values before the anesthesia, 5min after esmolol and saline administration, 3min after the induction and 30s, 2min and 4min after intubation. RESULTS: The corrected-QT interval was shorter in the esmolol group (p=0.012), the corrected-QT interval dispersion interval was longer in the control group (p=0.034) and the mean heart rate was higher in the control group (p=0.022) 30s after intubation. The risk of arrhythmia frequency was higher in the control group in the 4-min period following intubation (p=0.038). CONCLUSION: Endotracheal intubation was found to prolong corrected-QT interval and corrected-QT interval dispersion, and increase the heart rate during anesthesia induction with propofol in hypertensive patients using angiotensin converting enzyme inhibitors. These effects were prevented with esmolol (500mcg/kg bolus, followed by 100mcg/kg/min infusion). During induction, the blood pressure tends to decrease with esmolol where care is needed.
RESUMO
Es posible que las hospitalizaciones y las consultas a lasala de emergencias debidas a angioedema estén enaumento. En este estudio se determinó el patrón de losingresos hospitalarios por angioedema en el estado deNueva York para los años 1990 a 2005...
Hospitalizations and emergency visits due to angioedemamay be on the rise. In this study, the pattern of hospital admissions for angioedema in New York state were profiled for the years 1990 through 2005...
Assuntos
Angioedema , Hospitalização , Negro ou Afro-Americano , Anafilaxia , HipertensãoRESUMO
This study was designed to test the possible effects of a combination of physical and pharmacological therapy intervention on myocardial structure of the left ventricle in spontaneously hypertensive rats (SHR). Twelve weeks old spontaneously hypertensive rats (n = 40) were divided into four groups of sedentary, (Sed) as controls, exercise only (Exer), lisinopril only 20mg/kg/day (Lis), and exercise + lisinopril (LisExer). Exercise training was performed on a treadmill (5m/min.) for 60 minutes/day, 5 days/week for 10 weeks. At the end of 10 weeks, all the rats were terminally anaesthetised, the heart was arrested in diastole by intravenous procaine and whole animal perfusion fixation through the abdominal aorta was carried out using Karnovsky's fixative (pH 7.24). The heart was removed and left ventricle plus the interventricular septum was serially sectioned at a thickness of 3 mm. One piece was randomly chosen, and embedded in JB4 resin. Six sections were obtained from each block, stained with toluidine blue:acid fucin. Measurement of volume fraction (Vf), of myocardium, capillaries and interstitium were carried out using a stereology software (Histometrix MIL6 Kinetic imaging Ltd.). Mean Vf of capillaries in Sed group was 0.114 ± 0.01 (SEM). This was significantly increased in LisExer group. The Vf of muscle in Sed group was 0.795 ± 0.02 (SEM). This was significantly decreased in Lis but unchanged in Exer group. Capillaries Vf was significantly higher in LisExer as compared to Lis or Exer groups (p<0.05). Muscle Vf was not different betweenLisExer and Lis groups. The outcome of these changes could well be a better enhancement of cardiac performance in hypertension by combined exercise and ACE inhibitor treatment than either of the interventions alone.
Este estudio fue diseñado para probar los posibles efectos de una combinación de ejercicios y una intervención de terapia farmacológica en las estructuras del miocardio del ventrículo izquierdo, en ratas espontaneamente hipertensivas (SHR). Ratas de 20 semanas espontáneamente hipertensas (n = 40) fueron divididas en cuatro grupos: sedentarias (Sed) y controles, solamente con ejercicio (Ejer), solamente con lisinopril con 20mg/kg/día (Lis), y ejercicios + lisinopril (LisEjer). Los ejercicios fueron ejecutados en una máquina de entrenamiento (5m/min.) por 60 minutos/día, 5 días/semana por 10 semanas. Al término de las 10 semanas, las ratas fueron sacrificadas bajo anestesia, el corazón fue detenido en diástole usando procaina intravenosa. Los animales fueron perfundidos a través de la parte abdominal de la aorta, usando solución de Karnovsky (pH 7.24). El corazón fue removido y tanto al ventrículo izquierdo como al septo interventricular se les realizaron cortes seriados de 3 µm. Una pieza fue seleccionados al azar, y sumergida en resina JB4. Fueron obtenidas 6 secciones de cada bloque y luego teñidas con azul de toluidina:fucsina ácida. Las mediciones de fracción volumétrica (Vf) del miocardio, capilares, e intersticio fueron obtenidas usando un software de estereología (Histometrix MIL6 Kinetic imaging Ltd.). El promedio Vf de capilares en el grupo Sed, fue 0.114 ± 0.01 (SEM). Éste fue significativamente mayor en el grupo LisExer. El Vf de músculo en Sed fue 0.795 ± 0.02 (SEM). Éste fue significativamente menor en Lis pero no varió en el grupo Ejer. Vf capilares fue significativamente alto en LisExjr, si es comparado con los grupos Lis o Ejer (p<0.05). En Vf músculo no hubo diferencias entre los grupos LisEjer y Lis. El resultado de estos cambios pudo deberse a un mejor funcionamiento cardiaco en ratas hipertensa,s producto de ejercicios combinados y tratamiento con inhibidor ACE, que en aquellos en que se efectó un solo procedimiento.