Captopril inhibits thioacetamide-induced chronic liver injury associated with the suppression of inflammation / hypoxia- inducible factor 1-alpha / profibrogenic axis-mediated hepatotoxicity in rats / Captopril inhibe la lesión hepática crónica inducida por tioacetamida asociada con la supresión de la inflamación/factor 1-alfa inducible por hipoxia/hepatotoxicidad mediada por el eje profibrogénico en rata

SUMMARY: Liver transplantation is the only available method to treat liver failure induced by chronic liver injury. We sought to determine whether the angiotensin-converting enzyme inhibitor, captopril, can inhibit the development of chronic liver injury induced by the hepatotoxic agent thioacetamide (TAA) in association with the suppression of inflammation (hsCRP, TNF-α, and IL-6) / hypoxia- inducible factor 1-alpha (HIF-1α) / profibrosis (TIMP-1, MMP-9, and α-SMA) axis that mediates liver injury. Therefore, the model group of rats was injected for eight weeks with 200 mg/kg TAA starting at week two. The protective group was pretreated with 150 mg/ kg captopril daily for two weeks prior to TAA injections and continued receiving both capropril and TAA agents until being humanely scrificed at week 10. We observed a substantial damage to liver tissue in the model group as demonstrated by a significant (p<0.0001) increase in blood and hepatic tissue levels of high sensitivity C-reactive protein (hsCRP), tumor necrosis factor-a (TNF-α), interleukin- 6 (L-6), HIF-1α, tissue inhibitor of metalloproteinases-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), alpha-smooth muscle actin (α-SMA), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). All these parameters were significantly (p<0.0244) protected by captopril. Also, a significant (p<0.0001) positive correlation was observed between a-SMA (profibrosis) and the serum and tissue levels of hsCRP, TNF-α, HIF-1α, TIMP-1, MMP-9, and ALT. Thus, these findings suggest that the induction of chronic liver injury by the hepatotoxic compound, TAA is associated with the upregulation of inflammation/HIF-1α/profibrosis, with captopril exhibiting beneficial hepatic pleotropic effects.

El trasplante de hígado es el único método disponible para tratar la insuficiencia hepática inducida por una lesión hepática crónica. Buscamos determinar si el inhibidor de la enzima convertidora de angiotensina, captopril, puede inhibir el desarrollo de lesión hepática crónica inducida por el agente hepatotóxico tioacetamida (TAA) en asociación con la supresión de la inflamación (hsCRP, TNF-α e IL-6) / factor inducible por hipoxia 1-alfa (HIF-1α) / profibrosis (TIMP-1, MMP-9 y α- SMA) eje que media la lesión hepática. Por lo tanto, al grupo modelo de ratas se le inyectó durante ocho semanas 200 mg/kg de TAA a partir de la semana dos. El grupo protector fue pretratado con 150 mg/kg de captopril al día durante dos semanas antes de las inyecciones de TAA y continuó recibiendo capropril y agentes TAA hasta que fue sacrificado en la semana 10. Observamos un daño sustancial en el tejido hepático en el grupo modelo, como lo demuestra un aumento significativo (p<0,0001) de los niveles en sangre y tejido hepático de proteína C reactiva de alta sensibilidad (hsCRP), factor de necrosis tumoral-α (TNF-a), interleucina-6 (L-6), HIF-1α, inhibidor tisular de metaloproteinasas-1 (TIMP-1), metaloproteinasa de matriz-9 (MMP-9), actina de músculo liso alfa (α-SMA), alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST). Todos estos parámetros estaban significativamente (p<0,0244) protegidos por captopril. Además, se observó una correlación positiva significativa (p<0,0001) entre α-SMA (profibrosis) y los niveles séricos y tisulares de hsCRP, TNF-α, HIF-1α, TIMP- 1, MMP-9 y ALT. Por lo tanto, estos hallazgos sugieren que la inducción de daño hepático crónico por el compuesto hepatotóxico, TAA, está asociada con la regulación al alza de la inflamación/HIF-1α/profibrosis, con captopril exhibiendo efectos pleotrópicos hepáticos beneficiosos.

Inhibition of diabetes mellitus-induced knee joint injury in rats by a combination of metformin and captopril / Inhibición de la lesión de la articulación de la rodilla inducida por diabetes mellitus en ratas mediante una combinación de metformina y captopril

SUMMARY: Osteoarthritis (OA) is an inflammatory disease that damages the joints and affects millions of people worldwide. The potential inhibitory effects of the antidiabetic drug metformin combined with captopril, the angiotensin-converting enzyme inhibitor, on diabetes-induced damage to the knee joint articular cartilage associated with the inhibition of glycemia, dyslipidemia, and inflammation has not been investigated before. Therefore, we induced diabetes in rats using high carbohydrate and fat diets and a single injection of streptozotocin (50 mg/kg). The protective group of rats was pre-treated with combined daily doses of metformin (Met; 200 mg/kg body weight) and captopril (Cap; 150 mg/kg body weight) for 14 days before diabetic induction and continued on metformin and resveratrol until the end of the experiment at week 12. Harvested tissues obtained from knee joints were prepared for basic histology staining with haematoxylin and eosin (H&E) and examined under light microscopy. Representative H&E images showed that OA was developed in the diabetic rats as demonstrated by a profound damage to the knee joints such as irregular eroded and a sharp decrease in the thickness of the articular cartilage surface and abnormal remodeling of the subchondral bone that were substantially ameliorated by Met+Cap. Met+Cap also significantly (p< 0.05) reduced blood levels of glucose, glycated hemoglobin (HbA1c), dyslipidemia, and the inflammatory biomarkers, high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-α) induced by diabetes. In addition, a significant (p≤ 0.0014) correlation between the articular cartilage thickness and the blood levels of glucose, HbA1c, triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein- cholesterol (HDL-C), and hs-CRP were observed. Thus, we demonstrate that Met+Cap effectively protect the knee joint against injuries induced secondary to diabetes in rats, possibly due to the inhibition of glycemia, dyslipidemia, and biomarkers of inflammation.

RESUMEN: La osteoartritis (OA) es una enfermedad inflamatoria que daña las articulaciones y afecta a millones de per- sonas en todo el mundo. No se han investigado los posibles efectos inhibidores del fármaco antidiabético metformina combinado con captopril, el inhibidor de la enzima convertidora de angiotensina, sobre el daño inducido por la diabetes en el cartílago articular de la articulación de la rodilla asociado con la inhibición de la glucemia, dislipidemia e inflamación. En este estudio fue inducida la diabetes en ratas con dietas altas en carbohidratos y grasas y una sola inyección de estreptozotocina (50 mg / kg). El grupo protector de ratas se pretrató con dosis diarias combinadas de metformina (Met; 200 mg / kg de peso corporal) y captopril (Cap; 150 mg / kg de peso corporal) durante 14 días antes de la inducción diabética. El tratamiento se continuó con metformina y resveratrol hasta el final del experimento en la semana 12. Los tejidos obtenidos de las articulaciones de la rodilla se prepararon para la tinción de histología básica con hematoxilina y eosina (H&E) y se examinaron con microscopía óptica. Imágenes representativas de H&E mostraron que la OA se desarrolló en las ratas diabéticas, como lo evidencia un daño profundo en las articulaciones de la rodilla, como la erosión irregular y una fuerte disminución en el grosor de la superficie del cartílago articular y remodelación anor- mal del hueso subcondral que fueron mejorados sustancialmente por Met + Cap. Met + Cap. También redujo significativamente (p <0.05) los niveles sanguíneos de glucosa, hemoglobina glicosilada (HbA1c), dislipidemia y los biomarcadores inflamatorios, proteína C reactiva de alta sensibilidad (hs-CRP), interleucina-6 (IL-6), y factor de necrosis tumoral alfa (TNF-α) inducido por diabetes. Además, una correlación significativa (p≤ 0,0014) entre el grosor del cartílago articular y los niveles sanguíneos de glucosa, HbA1c, triglicéridos (TG), lipoproteínas-colesterol de baja densidad (LDL- C), lipoproteínas de alta densidad-colesterol (HDL-C) ) y hs-CRP. Así, demostramos que Met + Cap protege eficazmente la articulación de la rodilla contra lesiones inducidas por diabetes en ratas, posiblemente debido a la inhibición de la glicemia, dislipidemia y biomarcadores de inflamación.

Role of α2-adrenoceptors in the lateral parabrachial nucleus in the control of body fluid homeostasis

Central α2-adrenoceptors and the pontine lateral parabrachial nucleus (LPBN) are involved in the control of sodium and water intake. Bilateral injections of moxonidine (α2-adrenergic/imidazoline receptor agonist) or noradrenaline into the LPBN strongly increases 0.3 M NaCl intake induced by a combined treatment of furosemide plus captopril. Injection of moxonidine into the LPBN also increases hypertonic NaCl and water intake and reduces oxytocin secretion, urinary sodium, and water excreted by cell-dehydrated rats, causing a positive sodium and water balance, which suggests that moxonidine injected into the LPBN deactivates mechanisms that restrain body fluid volume expansion. Pretreatment with specific α2-adrenoceptor antagonists injected into the LPBN abolishes the behavioral and renal effects of moxonidine or noradrenaline injected into the same area, suggesting that these effects depend on activation of LPBN α2-adrenoceptors. In fluid-depleted rats, the palatability of sodium is reduced by ingestion of hypertonic NaCl, limiting intake. However, in rats treated with moxonidine injected into the LPBN, the NaCl palatability remains high, even after ingestion of significant amounts of 0.3 M NaCl. The changes in behavioral and renal responses produced by activation of α2-adrenoceptors in the LPBN are probably a consequence of reduction of oxytocin secretion and blockade of inhibitory signals that affect sodium palatability. In this review, a model is proposed to show how activation of α2-adrenoceptors in the LPBN may affect palatability and, consequently, ingestion of sodium as well as renal sodium excretion.

Eficacia de la microdosis de captopril en el tratamiento de la hipertensión arterial esencial / Effectiveness of captopril microdosing in the treatment of essential arterial hypertension

Introducción: prescribir una terapéutica adecuada siempre es complejo, más aun cuando los índices de control y la seguridad de los medicamentos no satisfacen los objetivos esperados, la microdosis pudiera convertirse en una alternativa eficaz. Objetivo: evaluar la eficacia de la microdosis de captopril en el tratamiento de la hipertensión arterial esencial. Métodos: se realizó un ensayo clínico fase III, unicéntrico, aleatorizado y controlado, en el Hospital Universitario Manuel Ascunce Domenech, de Camagüey, entre enero de 2007 y diciembre de 2009. Se creó un formulario con las variables: control clinico, grupos etarios, grado hipertensivo, grado de riesgo cardiovascular, dosis mínima necesaria para control. La información obtenida fue sometida a un procesamiento estadístico de análisis en el programa SPSS versión 15.0. Se utilizaron técnicas estadísticas para hallar diferencias entre variables. Resultados: la microdosis de captopril resultó ser más eficaz que las tabletas en el tratamiento a largo plazo de la hipertensión arterial, en particular en pacientes con 60 años y más de edad, en los hipertensos grados II y III y con más alto riesgo, aún con el uso de una dosis menor. Conclusiones: la microdosis de captopril fue eficaz en el tratamiento de la hipertensión arterial esencial, al permitir mejor control clínico con una menor dosis de medicamento

Introduction: prescribing the appropriate therapeutic treatment is always a complex task, particularly when drug control and safety indices do not accomplish the expected goals. In such a context, microdosing could be an effective alternative. Objective: evaluate the effectiveness of captopril microdosing in the treatment of essential arterial hypertension. Methods: aunicenter controlled randomized phase III clinical trial was conducted at Manuel Ascunce Domenech University Hospital in the province of Camagüey from January 2007 to December 2009. A form was prepared which included the following variables: clinical control, age group, hypertension grade, cardiovascular risk grade, minimum dose required for control. The information collected was subjected to statistical processing and analysis with the software SPSS versión 15.0. Statistical techniques were used to find differences between the variables. Results: captopril microdosing was more effective than tablets for the long-term treatment of arterial hypertension, particularly in patients aged 60 and over, grade II and III hypertensives, and higher risk patients, even with the use of a smaller dose. Conclusions: captopril microdosing was found to be effective for the treatment of essential arterial hypertension, allowing a better clinical control with a smaller dose of the medication

Padrões de prescrição de inibidores da enzima conversora da angiotensina para usuário do Sistema Único de Saúde / Prescription patterns of angiotensin converting enzyme inhibitors for unified health system users

Fundamentos: Os inibidores da enzima conversora da angiotensina são frequentemente prescritos para o tratamento da hipertensão arterial sistêmica e da insuficiência cardíaca congestiva. Os dois primeiros representantes dessa classe, o captopril e o enalapril, constam na Relação Nacional de Medicamentos Essenciais devido à eficácia clínica, segurança comprovada e custo-efetividade. Objetivo: Analisar os padrões de prescrição de captopril e de enalapril para os usuários do Sistema Único de Saúde no Distrito Sanitário Oeste de Ribeirão Preto. Métodos: Realizou-se um levantamento no banco de dados da Secretária Municipal de Saúde de Ribeirão Preto para quantificar os usuários do Sistema Único de Saúde que receberam a prescrição de captopril e do enalapril, a frequência de dispensação e analisaram-se os esquemas terapêuticos no peródo entre 01/03/2006 e 28/02/2007. Os dados foram submetidos à análise de variância e aos teste t de Student e de comparações múltiplas de médias. Resultados: Identificou-se que 9560 pacientes utilizaram os inibidores da enzima conversora da angiotensina, sendo quedestes, 46,57% utilizaram captopril, 45,74% enalapril e 7,69% os dois fármacos simultaneamente ou não. A idade média dos usuários foi 61 anos e a utilização desses agentes aumentou progressivamente com o aumento da faixa etária. As doses médias prescritas de captopril foram 69,9mg/dia e de enalapril, 21,35mg/dia e um total de 41,57% dos pacientes apresentaram risco de apresentar interação medicamentosa. Conclusões: Atualmente, existe uma preferência deprescrição de inibidores da enzima conversora da angiotensina em unidades públicas de saúde devido à sua relevânciaterapêutica para o tratamento de doenças crônicas.

Background: Angiotensin-converting enzyme inhibitors are often prescribed for the treatment of systemic arterialhypertension and congestive heart failure. The first two repesentatives of this class, enalapril and captopril, are inthe National Essential Drugs List because of their clinical efficacy, proven safety and cost effectiveness. Objective: To analyze the prescription patterns ofcaptopril and enalapril for Government Health System users in the West Public Health District of Ribeirão Preto, São Paulo State. Methods: A survey was conducted of the Ribeirão PretoMunicipal Health Bureau database, in order to quantify Government Health System users receiving prescriptionsfor captopril and enalapril, with dispensing frequency and therapeutic schemes between 01/03/2006 and28/02/2007. The data underwent variance analysis and Student t tests, with multiple mean comparisons. Results: 9,560 patients were identified as taking angiotensin-converting enzyme inhibitors, of whom 46.57% took captopril, 45.74% enalapril and 7.69% both medications, either simultaneously or not. The averagepatient age was 61 years and the use of these agents rose progressively with increasing age. The mean doses prescribed were 69.9 mg/day for captopril and 21.35 mg/day for enalapril, with 41.57% of patients at risk for potential drug-drug interactions.Conclusion: Currently, there is a preference for prescribing ACE inhibitors at public health units in Ribeirao Preto due to their therapeutic relevance for thetreatment of chronic diseases.

Kinetics of cardiac and vascular remodeling by spontaneously hypertensive rats after discontinuation of long-term captopril treatment

Angiotensin-converting enzyme inhibitors reduce blood pressure and attenuate cardiac and vascular remodeling in hypertension. However, the kinetics of remodeling after discontinuation of the long-term use of these drugs are unknown. Our objective was to investigate the temporal changes occurring in blood pressure and vascular structure of spontaneously hypertensive rats (SHR). Captopril treatment was started in the pre-hypertensive state. Rats (4 weeks) were assigned to three groups: SHR-Cap (N = 51) treated with captopril (1 g/L) in drinking water from the 4th to the 14th week; SHR-C (N = 48) untreated SHR; Wistar (N = 47) control rats. Subgroups of animals were studied at 2, 4, and 8 weeks after discontinuation of captopril. Direct blood pressure was recorded in freely moving animals after femoral artery catheterism. The animals were then killed to determine left ventricular hypertrophy (LVH) and the aorta fixed at the same pressure measured in vivo. Captopril prevented hypertension (105 ± 3 vs 136 ± 5 mmHg), LVH (2.17 ± 0.05 vs 2.97 ± 0.14 mg/g body weight) and the increase in cross-sectional area to luminal area ratio of the aorta (0.21 ± 0.01 vs 0.26 ± 0.02 ìm²) (SHR-Cap vs SHR-C). However, these parameters increased progressively after discontinuation of captopril (22nd week: 141 ± 2 mmHg, 2.50 ± 0.06 mg/g, 0.27 ± 0.02 ìm²). Prevention of the development of hypertension in SHR by using captopril during the prehypertensive period prevents the development of cardiac and vascular remodeling. Recovery of these processes follows the kinetic of hypertension development after discontinuation of captopril.

Potenciais interações medicamentosas em prescrições de um hospital-escola de Porto Alegre / Potential drug interactions among prescriptions of a teaching hospital in Porto Alegre

Introdução: Relatos das prevalências de interações medicamentosas em hospitais brasileiros são escassos. Objetivos: Descrever a prevalência de interações medicamentosas potenciais entre os fármacos prescritos nas enfermarias clínicas e cirúrgicas de um hospital-escola. secundariamente, descrever as características dessas interações e relacionar a sua ocorrência com o número de medicamentos prescritos e a idade dos pacientes. Pacientes e Métodos: Os dados foram coletados durante uma semana de out/2007, de 2a a 6a feira, a partir da última ficha de prescrição encontrada nos prontuários, envolvendo 128 fichas de prescrição com 10,5±4,1 fármacos. Os pacientes tinham 58,6±16,9 anos e 51,2% eram homens. A doença cardiovascular foi a enfermidade principal (23,4%) e a comorbidade (42,5%) mais frequentemente encontrada. A análise das interações foi feita através de consulta a um sistema interativo (Micromedex®). Resultados: 485 interações foram encontradas, estando presentes em 79,7% (IC95%: 72,6-86,8) das fichas de prescrição (média 3,8). A interação mais frequente foi captopril/dipirona (9,7%), seguida por dipirona/furosemida (4,5%), e os fármacos mais envolvidos foram dipirona (29,3%) e captopril (21,2%). A maioria das interações tinha mecanismo farmacodinâmico (65,5%), gravidade moderada (55,5%), começo tardio (61,3%) e bom embasamento científico (71,1%). A prevalência de interações esteve associada fortemente com o número de fármacos prescritos (r=0,65, p<0,001) e fracamente com a idade do paciente.

Introduction: Reports of the prevalence of drug interactions in Brazilian hospitals are scarce. Aims: To describe the prevalence of potential drug interactions among the medical drugs prescribed in the clinical and surgical units of a teaching hospital. Secondarily, to describe the characteristics of drug interactions and relate their occurrence to the number of prescribed medications and patient age. Patients and Methods: The data were collected from Monday to Friday of a week in Oct 2007, starting from the last prescription form found in the medical charts, and involved 128 prescription forms with 10.5±4.1 drugs. The patients’ mean age was 58.6±16.9 years and 51.2% were males. Cardiovascular disease was the main disease (23.4%) and the most frequently found comorbidity (42.5%). The analysis of interactions was done through consultation with an interactive system (Micromedex®). Results: 485 cases of drug interactions were found, being present in 79.7% (CI95%: 72.686.8) of the prescription forms (mean 3.8). The most frequent interaction was captopril/dipyrone (9.7%), followed by ipyrone/furosemide (4,5%), and the most frequently involved drugs were dipyrone (29.3%) and captopril (21.2%). Most of the interactions had a pharmacodynamic mechanism (65.5%), moderate severity (55.5%), late onset (61.3%), and a good scientific basis (71.1%). The prevalence of interactions was strongly associated with the number of drugs prescribed (r=0.65, p<0.001) and weakly associated with patient age.

Análise da prescrição de captopril em pacientes hospitalizados / Analysis of the prescription of captopril to hospitalized patients

Uma das complicações mais comuns da hipertensão arterial sistêmica é a crise hipertensiva¹ que se caracteriza por uma elevação sintomática da pressão arterial (PA), com ou sem envolvimento de órgãos-alvo, que pode conduzir a um risco imediato ou potencial de vida2-4. A crise hipertensiva pode se manifestar como emergência ou urgência hipertensiva. Na emergência, há a rápida deterioração de órgãos-alvo e risco imediato de vida, situação que não ocorre na urgência hipertensiva2-4. Além disso, as situações em que o paciente apresenta PA elevada diante de algum evento emocional, doloroso ou desconfortável, sem evidências de lesões de órgãos-alvo ou risco imediato de vida, caracterizam a pseudocrise hipertensiva, condição em que não é necessário o uso da terapia anti-hipertensiva de emergência1-3,5. Apesar disso, tem se tornado comum a prática de prescrever anti-hipertensivos precedendo situações em que se identifica algum risco de elevação abrupta da PA, independentemente de sintomas. O presente estudo tem como objetivo avaliar a freqüência de prescrição do captopril precedendo elevação da PA em pacientes internados em um hospital universitário. Pretende também mapear os locais (enfermarias clínicas ou cirúrgicas) onde essa conduta foi mais freqüente.

One of the most common complications of Systemic Arterial Hypertension is the hypertensive crisis¹ characterized by a symptomatic elevation of blood pressure (BP) with or without involvement of target organs, which may lead to immediate or potential risk to life2-4. The hypertensive crisis may manifest itself as hypertensive emergency or urgency. In the emergency there is fast deterioration of target organs and immediate risk to life, a situation that does not occur in hypertensive urgency2-4. On the other hand, situations in which the patient presents elevated BP due to an emotionally charged, painful or uncomfortable event, with no evidence of lesion of target organs or immediate risk to life, characterize the hypertensive pseudo-crisis, a condition that does not require the use of emergency antihypertensive therapy1-3,5. Despite this fact, the practice has become widespread of prescribing antihypertensive medication prior to situations believed to present a risk of abrupt BP elevation, irrespective of the symptoms. This study aims at assessing the frequency of prescription of captopril prior to BP elevation in patients hospitalized in a university hospital. It was also intended to map the places (clinical or surgical wards) where this procedure was more frequent.

The relationship between heart rate reserve and oxygen uptake reserve in heart failure patients on optimized and non-optimized beta-blocker therapy

BACKGROUND: The relationship between the percentage of oxygen consumption reserve and percentage of heart rate reserve in heart failure patients either on non-optimized or off beta-blocker therapy is known to be unreliable. The aim of this study was to evaluate the relationship between the percentage of oxygen consumption reserve and percentage of heart rate reserve in heart failure patients receiving optimized and non-optimized beta-blocker treatment during a treadmill cardiopulmonary exercise test. METHODS: A total of 27 sedentary heart failure patients (86 percent male, 50±12 years) on optimized beta-blocker therapy with a left ventricle ejection fraction of 33±8 percent and 35 sedentary non-optimized heart failure patients (75 percent male, 47±10 years) with a left ventricle ejection fraction of 30±10 percent underwent the treadmill cardiopulmonary exercise test (Naughton protocol). Resting and peak effort values of both the percentage of oxygen consumption reserve and percentage of heart rate reserve were, by definition, 0 and 100, respectively. RESULTS: The heart rate slope for the non-optimized group was derived from the points 0.949±0.088 (0 intercept) and 1.055±0.128 (1 intercept), p<0.0001. The heart rate slope for the optimized group was derived from the points 1.026±0.108 (0 intercept) and 1.012±0.108 (1 intercept), p=0.47. Regression linear plots for the heart rate slope for each patient in the non-optimized and optimized groups revealed a slope of 0.986 (almost perfect) for the optimized group, but the regression analysis for the non-optimized group was 0.030 (far from perfect, which occurs at 1). CONCLUSION: The relationship between the percentage of oxygen consumption reserve and percentage of heart rate reserve in patients on optimized beta-blocker therapy was reliable, but this relationship was unreliable in non-optimized heart failure patients.

Perfil do tratamento da insuficiência cardíaca na era dos betabloqueadores / Heart failure treatment profile at the beta blockers era

OBJETIVOS: A inibição dos sistemas renina-angiotensina-aldosterona (SRAA) e sistema nervoso autônomo simpático aumentou a perspectiva de sobrevida desses pacientes, além de permitir substancial melhora na qualidade de vida. O objetivo deste trabalho foi avaliar a realidade do tratamento aplicado e seu impacto sobre a doença em pacientes acompanhados em um ambulatório especializado em insuficiência cardíaca(IC). MÉTODOS: Foram estudados 96 pacientes acompanhados no ambulatório de Insuficiência Cardíaca e Transplante do Instituto do Coração, do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP). Os dados foram coletados durante a consulta ambulatorial a partir de prontuário médico e exame clínico. A escolha dos pacientes foi aleatória. RESULTADOS: A maior parte dos pacientes encontrava-se em classe funcional II (42,3 por cento) e em estágio C de evolução (94,9 por cento). A prescrição médica para os pacientes foi bastante próxima do preconizado pelas diretrizes. Aproximadamente 95 por cento recebem inibidores do SRAA (inibidor de ECA - enalapril e captopril - ou antagonista dos receptores de angiotensina-losartan), enquanto 85 por cento dos pacientes recebem, além desses, agentes betabloqueadores (carvedilol). A dose média prescrita também se aproxima das utilizadas nos grandes estudos, e atinge mais de 60 por cento da dose máxima de cada medicação. Os dados hemodinâmicos encontrados mostram pacientes estáveis, apesar da intensidade da disfunção e do remodelamento ventricular destes. CONCLUSÃO: Pacientes portadores de IC acompanhados por equipe médica especializada têm prescrição médica mais próxima do preconizado. Esses pacientes, embora com características marcadas de gravidade da doença, conseguem estabilidade hemodinâmica e clínica com a otimização terapêutica adequada.

OBJECTIVES: The inhibition of the rennin-angiotensin-aldosterone system (RAAS) and sympathetic autonomous nervous system has increased the perspective of survival in these patients, as well as allowing the improvement of the quality of life. The aim of this study was to evaluate the reality of the treatment employed and its impact on the disease in patients followed at a specialized heart failure (HF) outpatient clinic. METHODS: A sample of 96 patients followed at the HF and Transplant Outpatient Clinic of Heart Institute of the University of São Paulo School of Medicine (InCor -HCFMUSP) were evaluated. The data were collected during the ambulatory consultation from the medical files and through physical examination. Patients were randomly selected for the study. RESULTS: Most of the patients were Functional Class II (42.3 percent) and evolution stage C (94.9 percent). The medical prescription given to the patients was quite similar to the one recommended by the directives. Approximately 95 percent of them received RAAS inhibitors (ACE inhibitor - enalapril and captopril - or angiotensin receptor antagonist - losartan), whereas 85 percent of the patients additionally received beta blockers (carvedilol). The mean dose prescribed was also similar to the one used in large studies and reached more than 60 percent of the maximum dose for each medication. The hemodynamic data show that patients were stable, despite the intensity of the dysfunction and ventricular remodeling observed in these patients. CONCLUSION: Patients with HF followed by a specialized medical team receive a medical prescription that is closer to the recommended one. These patients, despite the marked characteristics of disease severity, achieve hemodynamic and clinical stability with an adequate therapeutic optimization.

Inhibitory Effect of Angiotensin Blockade on Hepatic Fibrosis in Common Bile Duct-ligated Rats / 대한간학회지

BACKGROUNDS AND AIMS: Angiotensin receptors are found on hepatic stellate cells, which participate in hepatic fibrosis. Therefore, it is presumed that angiotensin has a role in hepatic fibrosis. The aim of this study was to evaluate the effects of angiotensin blockade on inhibition of hepatic fibrosis in cirrhotic rat model. Material and METHODS: Cirrhosis with portal hypertension was produced by common bile duct ligation (BDL) in the adult Sprague-Dawley rats. They were classified into 4 groups (each group n=6) as follows; G1: BDL without drug, G2: BDL+captopril 100 mg/kg/day beginning 2 weeks after BDL, G3: BDL+captopril 100 mg/kg/day, starting just after BDL, G4: BDL+losartan 10 mg/kg/day, starting just after BDL. After 4 weeks following BDL, hepatic fibrosis was histomorphologically analyzed by Batts & Ludwig score. Alpha smooth muscle actin by immunohistochemical stain, hydroxyproline contents of liver tissue by spectrophotometry and expression of collagen, procollagen, and TGF-beta by real-time PCR were measured. RESULTS: Batts & Ludwig score were 3.8, 3.0, 2.6,and 2.6 in G1, G2, G3, and G4, respectively. The expression of alpha-SMA was significantly lower in G3 and G4 than in G1; 11.9%, 10.9%, 2.6%, and 1.1% in G1, G2, G3, and G4, respectively (p<0.05). The concentration of hydroxyproline (microgram/g liver tissue) was lower in G3 and G4 compared with G1 (p<0.05). Also, the administration of angiotensin blockade just after BDL significantly reduced the expression of collagen, procollagen, and TGF-beta mRNA. CONCLUSIONS: Angiotensin blockades are effective in the prevention of hepatic fibrosis in BDL rats.

Effect of chronic oral administration of a low dose of captopril on sodium appetite of hypothyroid rats: Influence of aldosterone treatment

Rats rendered hypothyroid by treatment with methimazole develop an exaggerated sodium appetite. We investigated here the capacity of hypothyroid rats (N = 12 for each group) to respond to a low dose of captopril added to the ration, a paradigm which induces an increase in angiotensin II synthesis in cerebral areas that regulate sodium appetite by increasing the availability of circulating angiotensin I. In addition, we determined the influence of aldosterone in hypothyroid rats during the expression of spontaneous sodium appetite and after captopril treatment. Captopril significantly increased (P<0.05) the daily intake of 1.8 percent NaCl (in ml/100 g body weight) in hypothyroid rats after 36 days of methimazole administration (day 36: 9.2 + or - 0.7 vs day 32: 2.8 + or - 0.6 ml, on the 4th day after captopril treatment). After the discontinuation of captopril treatment, daily 1.8 percent NaCl intake reached values ranging from 10.0 + or - 0.9 to 13.9 ± 1.0 ml, 48 to 60 days after treatment with methimazole. Aldosterone treatment significantly reduced (P<0.05) saline intake before (7.3 + or - 1.6 vs day 0, 14.4 + or - 1.3 ml) and after captopril treatment. Our results demonstrate that, although hypothyroid rats develop a deficiency in the production of all components of the renin-angiotensin-aldosterone system, their capacity to synthesize angiotensin II at the cerebral level is preserved. The partial reversal of daily 1.8 percent NaCl intake during aldosterone treatment suggests that sodium retention reduces both spontaneous and captopril-induced salt appetite

Nifedipina vs captopril en el manejo de las crisis hipertensivas administrados por vías sublingual en la emergencia de médicina interna entre octubre y diciembre de 1999

Se ingresaron al estudio un total de 30 pacientes, 13 varones (43.3 porciento), y 17 mujeres (56.7 porciento) los que dividierón en dos grupos terapeútico de 15 pacientes cada uno, siendo el grupo número de impares, los cuales fueron tratados con nifedipina 10mg por vía sublingual, la edad mínima de los pacientes fue de 41 añosy la máxima de 67 años para una edad promedio de 57.3 años, el grupo etáreo que aporto el mayor número de casos fue de 50 a 59 años con 16 pacientes (53.3 porciento) la asiganación de los números e ingresos de los grupos terapeútico se dio conforme el orden de consecuencia en busca de asistencia a la sala de emergencia de Médicina Interna del HEODRA, independientemente de la edad, sexo, motivo de la asistencia, siempre que el paciente llenara los criterios de ingreso y aceptara voluntariamente participar en el estudio. La edad minima de los pacientes fue de 41 años y la máxima de 67 años para una edad promedio de 57.3 años. El grupo etáreo que aporto mayor número de casos fue el de 50 a 59 años con 16 pacientes 53.3 porciento

Crisis de esclerodermia renal: rol de la vasculopatía esclerodérmica en la inducción de fibrosis cutáneo-visceral en dos casos / Renal scleroderma crisis: role of sclerodermic vasculopathy in the induction of cutaneous and visceral fibrosis: report of 2 cases

Although fibrosis and vasculopathy coexist in most patients with progressive systemic sclerosis, it is not clear if these events are the result of an unique etiologic factor or if one is consequence of the other. We report two cases of progressive systemic sclerosis that evolved to a renal scleroderma crisis. A 36 years old female presented with a Sjögren syndrome and painful subcutaneous nodules whose biopsy showed perivascular lymphocytic infiltration, perivascular thickening and normal skin. The ESR was 100 mm/h. She developed an hypertensive crisis and progressive renal failure, followed by a rapidly evolving progressive systemic sclerosis. The patient died in the course of this crisis. A 32 years old female with a progressive systemic sclerosis refractory to D-penicillamine treatment, receiving cyclosporin, presented a renal scleroderma crisis, that was successfully treated, with complete recovery of renal function. We highlight the different evolution of these cases, probably due to an early diagnosis and a better experience in the management of this condition

Hemodynamic responses to captopril during splenectomy in thalassemic children.

Splenectomy in beta-thalassemic children is frequently accompanied by perioperative hypertension which occasionally is followed by convulsion. The efficacy of captopril in attenuating the hypertensive response to splenectomy was investigated in 82 thalassemic children. The control group, consisting of 40 patients, received intravenous furosemide (1 mg/kg) preoperatively; whereas, 42 children were randomly allocated into 2 groups to receive oral captopril (0.7 mg/kg) or a combination of captopril (0.7 mg/kg) and furosemide (1 mg/kg) before the operation. Before anesthetic induction, both systolic and diastolic arterial pressures in the captopril and the combined groups were significantly lower than the furosemide group (P < 0.001), whereas, the heart rates in all groups were comparable. Changes in arterial pressure in response to the operation were significantly smaller in the combined group when compared with the other two groups (P < 0.001). Immediate postoperative hypertension requiring additional management occurred in 20 per cent of the furosemide group, and 14.3 per cent in the other two groups. One patient in the combined group had a convulsion in association with hypertension. The authors conclude that captopril combined with furosemide effectively controls intraoperative hypertension in thalassemic children undergoing splenectomy; however, postoperative hypertension remains common, and needs appropriate treatment immediately.

Inhibidores de la enzima convertidora de la angiotensina y bloqueantes de calcio en la nefropatía diabética incipiente / Enzyme inhibitors angiotensin convertinig and some calcium in the incipient nephropathy

Estudios clínicos han demostrado que los inhibidores de la enzima convertidora de la angiotensina (IECA) y algunos bloqueantes de calcio (BC) preservan la función renal. En este trabajo se estudia el efecto del IECA captopril y BC verapamil, solos o combinados, en pacientes diabéticos tipo 2 con o sin nefropatía incipiente. Para ello se seleccionaron 125 individuos al azar en cuatro grupos, recibiendo el grupo A captopril (12,5mg vo bid), grupo B verapamil (40mg vo bid), grupo C captopril y verapamil a las mismas dosis y el grupo D placebo. Fueron seguidos durante 20 meses, con evaluaciones cada 5 meses. Se produjo una disminución de la proteinuria en 24 horas en los tres grupos con intervención medicamentosa, siendo este descenso más significativo en el grupo A. Podemos afirmar que la terapia con captopril, sólo o en combinación con verapamil, ejerce un efecto renoprotector en diabéticos tipo 2 que presentan nefropatía lo que puede evidenciarse por la reducción en la proteinuria y microalbuminuria e incremento en la depuración de creatinina; estos efectos son independientes de los observados en la tensión arterial. Se recomienda que todos los pacientes diabéticos no insulinodependientes además de su control metabólico, deben ser tratados tengan o no hipertensión arterial con captopril desde el momento en que se diagnostica la diabetes