Associação entre o Antagonismo do Sistema Renina-Angiotensina-Aldosterona e a Mortalidade Relacionada à COVID-19 em Pacientes com Hipertensão Relacionada ao Sobrepeso/Obesidade: um Estudo Retrospectivo de Coorte / Association between RAAS Antagonism and COVID-19-related Mortality in Patients with Overweight/Obesity-related Hypertension: A Retrospective Cohort Study

Resumo Fundamento Os bloqueadores dos receptores da angiotensina (BRA) e os inibidores da enzima conversora da angiotensina (IECA) aumentam a expressão de ACE2, que é um receptor para entrada de SARS-CoV-2 nas células. Embora as evidências sugiram que os IECA/BRA são seguros entre a população geral com COVID-19, sua segurança em pacientes com hipertensão relacionada ao sobrepeso/obesidade merece uma avaliação mais aprofundada. Objetivo Avaliamos a associação entre o uso de IECA/BRA e a gravidade da COVID-19 em pacientes com hipertensão relacionada ao sobrepeso/obesidade. Métodos O presente estudo incluiu 439 pacientes adultos com sobrepeso/obesidade (índice de massa corporal ≥ 25 kg/m2) e hipertensão, diagnosticados com COVID-19 e internados no University of Iowa Hospitals and Clinic entre 1º de março e 7 de dezembro de 2020. Foram avaliadas a mortalidade e a gravidade da COVID-19 com base no tempo de internação hospitalar, internação em unidade de terapia intensiva, uso de oxigênio suplementar, ventilação mecânica e uso de vasopressores. A regressão logística multivariável foi usada para examinar as associações do uso de IECA/BRA com a mortalidade e outros marcadores de gravidade de COVID-19, com um alfa bilateral definido em 0,05. Resultados A exposição aos BRA (n = 91) e IECA (n = 149) antes da hospitalização foi significativamente associada a menor mortalidade ( odds ratio [OR] = 0,362, intervalo de confiança [IC] de 95% 0,149 a 0,880, p = 0,025) e menor tempo de internação hospitalar (IC 95% −0,217 a −0,025, p = 0,015). Adicionalmente, os pacientes em uso de IECA/BRA apresentaram uma tendência não significativa de menor internação em unidade de terapia intensiva (OR = 0,727, IC 95% 0,485 a 1,090, p = 0,123), uso de oxigênio suplementar (OR = 0,929, IC 95% 0,608 a 1,421,p = 0,734), ventilação mecânica (OR = 0,728, IC 95% 0,457 a 1,161, p = 0,182) e vasopressores (OR = 0,677, IC 95% 0,430 a 1,067, p = 0,093). Conclusão Os resultados sugerem que pacientes internados com COVID-19 e hipertensão relacionada ao sobrepeso/obesidade que receberam IECA/BRA antes da internação apresentam menor mortalidade e COVID-19 menos grave do que aqueles que não estavam tomando IECA/BRA. Os resultados também sugerem que a exposição aos IECA/BRA pode proteger pacientes com hipertensão relacionada ao sobrepeso/obesidade de COVID-19 grave e morte.

Abstract Background Angiotensin receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI) increase the expression of ACE2, which is a receptor for entry of SARS-CoV-2 into cells. Though evidence suggests that ARB/ACEI are safe among the general population with COVID-19, their safety in patients with overweight/obesity-related hypertension deserves further evaluation. Objective We assessed the association between ARB/ACEI use and COVID-19 severity in patients with overweight/obesity-related hypertension. Methods This study included 439 adult patients with overweight/obesity (body mass index ≥ 25 kg/m2) and hypertension, diagnosed with COVID-19 and admitted to University of Iowa Hospitals and Clinic from March 1 to December 7, 2020. Mortality and severity of COVID-19 were evaluated based on length of stay in hospital, intensive care unit admission, use of supplemental oxygen, mechanical ventilation, and vasopressors. Multivariable logistic regression was used to examine the associations of ARB/ACEI use with mortality and other markers of COVID-19 severity, with a two-sided alpha set at 0.05. Results Exposure to ARB (n = 91) and ACEI (n = 149) before hospitalization was significantly associated with lower mortality (odds ratio [OR] = 0.362, 95% confidence interval [CI] 0.149 to 0.880, p = 0.025) and a shorter length of stay (95% CI −0.217 to −0.025, p = 0.015). Additionally, patients using ARB/ACEI showed a non-significant trend toward lower intensive care unit admission (OR = 0.727, 95% CI 0.485 to 1.090, p = 0.123), use of supplemental oxygen (OR = 0.929, 95% CI 0.608 to 1.421, p = 0.734), mechanical ventilation (OR = 0.728, 95% CI 0.457 to 1.161, p = 0.182), and vasopressors (OR = 0.677, 95% CI 0.430 to 1.067, p = 0.093). Conclusion Results suggest that hospitalized patients with COVID-19 and overweight/obesity-related hypertension who were prescribed ARB/ACEI before admission to the hospital exhibit lower mortality and less severe COVID-19 than those who were not taking ARB/ACEI. The results also suggest that exposure to ARB/ACEI may protect patients with overweight/obesity-related hypertension from severe COVID-19 and death.

The use of angiotensin receptor blockers in dementia prevention / O uso de bloqueadores de receptor de angiotensina na prevenção de demência

ABSTRACT: Alzheimer's disease (AD) and dementia are preventable and highly prevalent diseases, as is systemic arterial hypertension. Thus, it is speculated that angiotensin receptor blockers (ARBs) may be neuroprotective against AD. Objective: The aim of this study was to evaluate if the use of ARBs confers a neuroprotective effect on AD, through a systematic review. Methods: Studies published on Embase, LILACS, SciELO, and PubMed were evaluated. The selection of the studies included those that evaluated the use of antihypertensive drugs in individuals with a previous diagnosis of mild cognitive impairment. The data were extracted with the Cochrane Effective Practice and Organization of Care (EPOC) form. The risk of bias was evaluated by the EPOC "Risk of bias tool." Results: A total of 12 articles were identified, and 3 articles were selected. Two of them analyzed the use of ARB/ACEI versus other antihypertensives and the development of dementia. Conclusion: There is a tendency for ARBs to be superior to other antihypertensives in preventing dementia.

RESUMO: A doença de Alzheimer (DA) e a demência são doenças potencialmente preveníveis, assim como a hipertensão arterial sistêmica. Dessa forma, especula-se que os bloqueadores dos receptores de angiotensina (BRA) tenham efeito neuroprotetor contra a DA. Objetivo: Avaliar se o uso de BRA confere efeito neuroprotetor para DA, por meio de uma revisão sistemática. Métodos: Foram avaliados estudos publicados nas plataformas Embase, Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs), Scientific Electronic Library Online (SciELO) e United States National Library of Medicine (PubMed). Os estudos incluídos avaliaram o uso de anti-hipertensivos em indivíduos com diagnóstico prévio de comprometimento cognitivo leve. Os dados foram extraídos com base no formulário da EPOC. Risco de viés foi avaliado por meio da ferramenta da Cochrane Effective Practice and Organisation of Care (EPOC) "Risk of bias tool". Resultados: Foram encontrados 12 artigos e três foram selecionados. Dois analisaram o uso de BRA/IECA vs. o uso de outros anti-hipertensivos e o desenvolvimento de demência. Conclusão: Há uma tendência de que os BRA sejam superiores a outros anti-hipertensivos na prevenção da demência.

Uso previo de antagonistas de la angiotensina II en pacientes hipertensos hospitalizados y mortalidad por COVID-19

Introducción: Actualmente existe un gran interés en establecer la relación entre la severidad de la infección por SARS-COV-2 en pacientes hipertensos usuarios de antagonistas de la angiotensina II (ARAII). Objetivo: Estudiar la relación entre el uso previo de antagonistas de la ARA II en pacientes hipertensos y la mortalidad por COVID-19. Materiales y métodos: Se realizó un estudio observacional retrospectivo en un hospital de referencia en Lima, Perú, en pacientes hipertensos hospitalizados en marzo del 2021 por COVID-19 severo. Resultados: Ingresaron al estudio 101 pacientes, con una media de edad de 70.1 + 12.0 y sexo masculino 48%. Los usuarios de ARAII fueron 45 (45.6%) y no los tomaban 56 (54.4%). El Índice de comorbilidad de Charlson fue mayor en el grupo ARAII (3.6 + 1.56 vs 3.04 + 1.24) (p<0.05). La mortalidad total y por sexo (varones vs mujeres), entre los que usaban ARAII o no, fueron 57.8% vs 62% (p = 0.633) y 36.36% vs 63.64 % (p<0.05), respectivamente. La media de la concentración de deshidrogenasa láctica fue menor en los que tomaban ARAII comparado con los no usuarios, 394.18 + 152.3 vs 503.5 + 252.7 (p<0.05); no se observó diferencia significativa en el recuento de leucocitos, niveles séricos de Proteína C Reactiva, Ferritina, dímero D y fibrinógeno. Conclusión: Entre los pacientes hospitalizados con COVID-19 con hipertensión, el uso previo de ARAII no se asoció con riesgo de mortalidad.

Background: There is caurrently great interest in establishing the relationship between the severity of SARS-COV-2 infection in hypertensive patients who use angiotensin II antagonists (AIIRAs). Objective: To study the relationship between the previous use of angiotensin II antagonists (ARB) in hypertensive patients and mortality from COVID-19. Materials and methods: A retrospective observational study was carried out in a tertiary care hospital in Lima, Peru, in hypertensive patients hospitalized in March 2021 for severe COVID-19. Results: A total of 101 patients entered the study, with a mean age of 70.1 + 12.0 and 48% male. ARB users and non-users were 45 (45.6%) and 56 (54.4%), respectively. The Charlson Comorbidity Index was higher in the ARB group (3.6 + 1.56 vs 3.04 + 1.24) (p<0.05). Total and male vs women mortality, among those using ARBs or not, were 57.8% vs 62% (p = 0.633) and 36.36% vs 63.64% (p <0.05), respectively. Mean lactate dehydrogenase concentration was lower in those taking ARBs compared to non-users, 394.18 + 152.3 vs 503.5 + 252.7 (p<0.05); No significant difference was observed in the leukocyte count and serum levels of C-Reactive Protein, Ferritin, D-dimer and fibrinogen. Conclusion: Among hospitalized COVID-19 patients with hypertension, prior use of ARBSs was not associated with mortality risk.

Pronóstico de los pacientes hospitalizados por Covid-19 que utilizaban inhibidores de la enzima convertidora de angiotensina o antagonistas del receptor de angiotensina II / Prognósis of patients hospitalized due to Covid-19 who were taking angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers

Introducción: existe controversia acerca de la seguridad del uso de inhibidores de la enzima convertidora de angiotensina (iECA) o antagonistas de los receptores de angiotensina II (ARA II) en pacientes con COVID-19, debido a que la ECA-2 sirve de entrada del virus a la célula. Objetivo: evaluar la asociación del antecedente del uso de iECA o ARA II con el ingreso a UCI o la muerte intrahospitalaria. Metodología: cohorte prospectiva multicéntrica que incluyó pacientes adultos hospitalizados por coronavirus COVID-19 en tres hospitales de Bogotá, Colombia, entre abril y noviembre 2020. Se realizó un análisis univariado evaluando la asociación de los iECA y ARA II con el ingreso a UCI o la muerte intrahospitalaria. Resultados: se incluyeron 592 pacientes de los cuales 225 (38.0%) cursaban con hipertensión arterial, 108 (18.2%) diabetes y 50 (8.4%) enfermedad cardiovascular crónica, 160 (27.0%) ingresaron a UCI y 107 (18.1%) fallecieron, 32% tenía el antecedente de uso de iECA o ARA II. En el análisis univariado no se obtuvo ninguna asociación con ingreso a UCI o muerte intrahospitalaria, uso de inhibidores de la ECA OR= 1.017 (IC95% 0.887 - 1.152, p=0.800), OR=1.072 (0.952 - 1.19, p=0.968) respectivamente; uso de ARA II OR= 0.998 (IC95% 0.913-1.086, p=0.968), OR=1.045 (IC95% 0.969 - 1.122, p=0.235), respectivamente. Conclusiones: el antecedente del uso de los iECA o ARA II no se asoció con el ingreso a UCI o la muerte intrahospitalaria en pacientes hospitalizados por COVID-19.

Introduction: controversy remains about the safety of using angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) in patients with COVID-19, since ACE2 receptor mediates the entry of the virus into the cell. Objective: to evaluate the association of past history of ACEIs or ARBs use with admission to the ICU or in-hospital death. Methodology: prospective multicenter cohort that included adult patients hospitalized due to COVID-19 coronavirus in three hospitals in Bogota, Colombia, between April and November 2020. A univariate analysis was performed evaluating the association of ACEIs and ARBs with ICU admission or in-hospital death. Results: 592 patients were included of whom 225 (38.0%) had hypertension, 108 (18.2%) diabetes and 50 (8.4%) chronic cardiovascular disease, 160 (27.0%) were admitted to the ICU and 107 (18.1%) died, 32% had a history of prior ACEIs or ARBs use. In the univariate analysis no association was found with ICU admission or in-hospital death, ACEIs use OR= 1.017 (CI95% 0.887 - 1.152, p=0.800), OR=1.072 (0.952 - 1.19, p=0.968) respectively; use of ARBs OR= 0.998 (CI95% 0.913-1.086, p=0.968), OR=1.045 (CI95% 0.969 - 1.122, p=0.235), respectively. Conclusions: a history of prior ACEIs or ARBs use was not associated with admission to the ICU or in-hospital death in patients hospitalized due to COVID-19.

Receptor de la enzima convertidora de angiotensina y su correlación con COVID-19 ¿Qué conocemos hasta el momento? / Angiotensin Converting Enzime Receptor and COVID-19 Correlation ¿What do we know so far?

Resumen Introducción: el SARS-COV-2 es un nuevo virus que ha traído nuevos retos a los sistemas de salud a nivel mundial y que ha generado controversia en la continuidad en el uso de bloqueadores del receptor de angiotensina por su correlación fisiopatológica con el SARS-COV-2. Objetivo: presentar la evidencia disponible y las actuales recomendaciones sobre el uso de receptores de la enzima convertidora de angiotensina en el tratamiento para COVID-19. Materiales y métodos: se realizó una búsqueda narrativa en la base de datos PubMed sobre artículos que hablaran acerca del receptor de la enzima convertidora de angiotensina asociado a la pandemia actual por COVID-19. El límite de publicación fue el 13 de abril de 2020 y se incluyeron artículos en todos los idiomas. Resultados: se encontraron 14 artículos con contenido científico significativo para el objetivo de la presente revisión. Conclusión: la fisiopatología del SARS-COV-2 aún es desconocida, así como la efectividad de diferentes fármacos de uso cotidiano para su tratamiento. Dentro de los diferentes medicamentos que se han probado para detener el contagio y sus efectos están aquellos con efecto sobre el receptor de la enzima convertidora de angiotensina.

Abstract Introduction: As a new disease, SARS-COV-2 is a new challenge for healthcare system worldwide, with physiopathology under study and controversy about Angiotensin Converting Enzyme Blockers use because of It's physiopatological correlation with SARS-Cov-2. Objetive: Search for novel literature and recent recomendations about use of Angiotensin Converting Enzyme Blockers during Covid-19 illness. Materials and Methods: We look for narrative literature at PubMed Database for articles about Angiotensin Converting Enzyme and Covid-19 pandemic. Searching limit was April 13 of2.020, we included all languages. Results. We included 14 articles with significative scientific content for review objetive. Conclusion: SARS-Cov-2 Physiopatology is still unclear, also, pharmacology effectiveness in it's treatment. One of these pharmacology groups are the Angiotensin Converting Enzyme Blockers with uncertainty about it's safety during COVID-19 illness.

Recomendación rápida sobre el uso de antihipertensivos IECA/ARA II en pacientes con riesgo o documentación de COVID-19 / Rapid recommendation on the use of ACEI/ARA antihypertensives in patients at risk or with documented COVID-19

Ciertos hallazgos preclínicos generaron preocupación en la comunidad científica y en la población general sobre el uso de inhibidores de la enzima convertidora de angiotensina (IECA) y los antagonistas del receptor de la angiotensina II (ARAII), y los posibles desenlaces adversos asociados con relación a la infección por el nuevo Coronavirus (SARS-Cov-2).Por este motivo, nos planteamos como objetivo proveer de recomendaciones dinámicas (living recommendations) para el tratamiento con fármacos IECA o ARA II en pacientes con riesgo o documentación de infección por SARS-CoV-2 (en todo su espectro de gravedad). Se utilizó como metodología la adaptación/adopción de guías de práctica clínica bajo el enfoque GRADE, actualizando la evidencia al 7 de abril de 2020 mediante búsquedas en múltiples bases de datos y consultando a un panel multidisciplinario libre de conflictos de interés. Como resultado de este proceso se arribó a la siguiente afirmación: se recomienda, en contexto de la pandemia de COVID-19, en personas que se encuentran en tratamiento con IECA/ARAII, mantener el tratamiento sin cambios por sobre suspenderlo o reemplazarlo por otros fármacos (Recomendación fuerte a favor - calidad de evidencia baja). (AU)

Certain preclinical findings raised concerns in the scientific community and in the general population about the use ofangiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists (ARA) and the possible adverse outcomes associated with the infection with the new Coronavirus (SARS-Cov-2). For this reason, our objective is to provide living recommendations for treatment with ACEI or ARA in patients with risk or documentation of SARS-CoV-2 infection (inall its severity spectrum). The adaptation/adoption of clinical practice guidelines under the GRADE approach was used as a methodology, updating the evidence as of April 7, 2020, by searching multiple databases and consulting a multidisciplinary panel free of conflicts of interest. As a result of this process, the following statement was reached: it is recommended, in the context of the COVID-19 pandemic, in people who are undergoing treatment with ACEI/ARA, to maintain the treatment unchanged instead of its suspension or replacement with other drugs (Strong recommendation in favor - low quality ofevidence). (AU)

Improved histoarchitectural changes with angiotensin receptor blockers in early testicular and cauda toxicity in rats / Mejora de los cambios en la histoarquitectura con bloqueadores de receptores de angiotensina en la toxicidad precoz testicular y de cauda en ratas

SUMMARY: Reproductive dysfunction is a complication for many diseases and toxins. Its early diagnosis and treatment are immensely important. Here the morphological histoarchitecture changes in early testicular and cauda toxicity before and after treatment with angiotensin receptor blockers were evaluated. Low-grade testicular damage was induced using thioacetamide (TAA, 50 mg/kg/day) intraperitoneally for two weeks in rats. The rats were randomly divided into four groups (n = 8) treated daily orally for three weeks as follows: Normal control (distilled water), TAA (positive control), TAA+candesartan (0.2 mg/kg) and TAA+losartan (7.5 mg/kg). Serum testosterone and testicular malondialdehyde and glutathione were measured. The changes in histoarchitecture of testis and cauda epididymis were evaluated by hematoxylin and eosin for general structure, Masson's trichrome for collagen, periodic acid Schiff for basement membrane, and caspase-3 and proliferating cell nuclear antigen (PCNA) for immunohistochemical analysis. The TAA-rats showed decreases of serum testosterone and testicular glutathione, increases in testicular malondialdehyde, degenerative changes and apoptosis in germ cells, thickening of tubular basal lamina and increases in expression of caspase 3, and decreases in expression of PCNA. The ARBs (candesartan and losartan) significantly reversed these changes with non-significant differences in-between. Treatment with ARBs (candesartan and losartan) significantly reversed TAA-induced low-grade testicular and cauda toxicity in rats. This could be potentially useful for early treatment of male patients with occupational toxicant-induced reproductive dysfunction especially if they are using ARBs for other comorbidities.

RESUMEN: La disfunción reproductiva es una complicación por muchas enfermedades y toxinas. Su diagnóstico y tratamiento tempranos son inmensamente importantes. Aquí se evaluaron los cambios morfológicos en la histoarquitectura en la toxicidad precoz testicular y cauda antes y después del tratamiento con bloqueadores de receptores de angiotensina. Se indujo daño testicular de bajo grado usando tioacetamida (TAA, 50 mg / kg / día) por vía intraperitoneal durante dos semanas en ratas. Las ratas se dividieron aleatoriamente en cuatro grupos (n = 8) tratados diariamente por vía oral durante tres semanas de la siguiente manera: control normal (agua destilada), TAA (control positivo), TAA + candesartan (0,2 mg / kg) y TAA + losartán (7,5 mg / kg). Se midieron la testosterona sérica, el malondialdehído testicular y el glutatión. Los cambios en la histoarquitectura de los testículos y la epidermis de la cauda se evaluaron mediante Hematoxilina y Eosina para determinar la estructura general, con tricrómicro de Masson para el colágeno, ácido periódico de Schiff para la membrana basal y la caspasa-3 y el antígeno nuclear de células proliferantes (PCNA) para análisis inmunohistoquímico. Las ratas TAA mostraron disminución de la testosterona sérica y glutatión testicular, aumentos en el malondialdehído testicular, cambios degenerativos y apoptosis en células germinales, engrosamiento de la lámina basal tubular y aumentos en la expresión de la caspasa 3, y disminución en la expresión de PCNA. Los ARB (candesartán y losartán) revirtieron significativamente estos cambios con diferencias no significativas en el medio. El tratamiento con BRA (candesartán y losartán) revirtió significativamente la toxicidad testicular y cauda inducida por TAA en ratas. Esto podría ser potencialmente útil para el tratamiento temprano de pacientes con disfunción reproductiva inducida por tóxicos ocupacionales, especialmente si están usando BRA para otras comorbilidades.

Urinary cytokine profiles according to the site of blockade of the renin-angiotensin system in nephrectomized rats / Perfil de citocinas urinárias de acordo com o local de bloqueio do sistema renina angiotensina em ratos nefrectomizados

Abstract Introduction: It is still unknown how the pharmacological inhibition of the Renin Angiotensin System (RAS) impacts the levels of inflammation and fibrosis biomarkers. Objective: This study sought to evaluate the effect of enalapril, candesartan and aliskiren on urinary levels of cytokines in a model of chronic kidney disease (CKD). Methods: Male Wistar rats were submitted to surgical removal of ¾ of renal parenchyma to induce CKD (¾ nephrectomy), or subjected to sham surgery (control). Animals were then randomized into five groups: Sham surgery receiving vehicle; ¾ Nephrectomy receiving vehicle; ¾ Nephrectomy receiving enalapril (10 mg/kg); ¾ Nephrectomy receiving candesartan (10 mg/kg) and ¾ Nephrectomy receiving aliskiren (10 mg/kg). Urine output, water intake, mean arterial pressure (MAP) and urinary concentrations of creatinine, urea, albuminuria, Na+, K+, interleukin (IL) -1β, IL-6, IL-10 and transforming growth factor beta (TGF-β) were measured. Results: Nephrectomy significantly impaired renal function, increased MAP and altered the levels of all evaluated cytokines in urine. Enalapril, candesartan and aliskiren improved renal function and decreased MAP and IL-6 when compared to vehicle-treated nephrectomized group. Candesartan and aliskiren decreased IL-1β, while only candesartan reduced TGF-β and only aliskiren increased IL-10. Conclusion: Enalapril, candesartan and aliskiren presented similar effects on improving renal function and reducing MAP and urinary levels of IL-6 in rats with CKD. On the other hand, cytokine profile differed according to the treatment, suggesting that differential mechanisms were triggered in response to the site of RAS blockade.

Resumo Introdução: Ainda não se sabe como a inibição farmacológica do Sistema Renina Angiotensina (SRA) afeta os níveis de biomarcadores de inflamação e fibrose. Objetivo: Este estudo pretendeu avaliar o efeito de enalapril, candesartan e alisquireno sobre os níveis urinários de citocinas em um modelo de doença renal crônica (DRC). Métodos: Ratos Wistar machos foram submetidos à remoção cirúrgica de ¾ do parênquima renal para induzir DRC (nefrectomia), ou submetidos à cirurgia fictícia (controle). Animais foram então randomizados em cinco grupos: Cirurgia fictícia recebendo veículo; Nefrectomia recebendo veículo; Nefrectomia recebendo enalapril (10 mg/kg); Nefrectomia recebendo candesartan (10 mg/kg) e Nefrectomia recebendo alisquireno (10 mg/kg). Débito urinário, ingesta hídrica, pressão arterial media (PAM) e concentrações urinárias de creatinina, ureia, albumina, Na+, K+, interleucina (IL) -1β, IL-6, IL-10 e fator de transformação e crescimento beta (TGF-β) foram medidas. Resultados: A nefrectomia comprometeu significativamente a função renal, aumentou a PAM e alterou os níveis de todas as citocinas avaliadas na urina. Enalapril, candesartan e alisquireno melhoraram a função renal e diminuíram a PAM e a IL-6 quando comparado aos grupo de animais nefrectomizados tratados com veículo. Candesartan e alisquireno reduziram IL-1β, enquanto somente candesartan diminuiu o TGF-β e somente alisquireno aumentou a IL-10. Conclusão: Enalapril, candesartan e alisquireno apresentaram efeitos similares em relação à melhora da função renal e redução da PAM e dos níveis urinários de IL-6 em ratos com DRC. Por outro lado, o perfil de citocinas diferiu de acordo com o tratamento, sugerindo que diferentes mecanismos sejam desencadeados em resposta ao local de bloqueio do SRA.

Schistosoma mansoni associated glomerulopathy with IgA mesangial deposits: case report / Glomerulopatia esquistossomótica com depósitos mesangiais de IgA: relato de caso

Abstract Introduction: Renal involvement is a severe form of schistosomiasis and occurs in 10% to 15% of patients with the hepatosplenic form of the disease. Nephrotic syndrome is the most common clinical presentation. It is a complication caused by immune complexes (IC), it is rare to appear in the Brazilian context with a immunoglobulin A (IgA) deposits. When installed the renal injury by Schistosoma mansoni, classically presents as membranoproliferative glomerulonephritis (mesangiocapillary) with lobular accentuation. Objective: To report a case of schistosomiasis nephropathy that appeared 7 years after treatment of hepatosplenic schistosomiasis with histologic pattern of mesangial proliferative glomerulonephritis with IgA deposits in mesangium. Clinically developed with progressive decrease of proteinuria with angiotensin receptor blocker (ARB). Method: It was reported a case of a 36 years old patient, brown, with classical sintoms of nephrotic syndrome (proteinuria > 3.5 g/24h, hypoalbuminemia and hypercholesterolemia), however with hepatosplenic schistosomiasis history 7 years ago and portal hypertension. Patient underwent renal biopsy which showed IgA deposits in mesangial, being more intense than immunoglobulin G (IgG), accompanied by C1q and C3, with 4/13 glomeruli sclerotic, standard light mesangial glomerulonephritis renal injury with IgA deposits. Patient began taking ARB with progressive improvement in proteinuria. Conclusion: Patients with glomerulonephritis by schistosoma don't show improvement of disease progression with antiparasitic treatment. However the anti-proteinuric treatment can slow the progression of end stage kidney disease.

Resumo Introdução: O acometimento renal é uma forma grave da esquistossomose e ocorre em 10% a 15% dos pacientes com a forma hepatoesplênica da doença. A síndrome nefrótica é a apresentação clínica mais comum. Trata-se de uma complicação causada por imunocomplexos (IC), sendo rara no contexto brasileiro apresentar-se com depósitos de imunoglobulina A (IgA). Quando instalada a lesão renal pelo Schistosoma mansoni, apresenta-se classicamente como glomerulonefrite membranoproliferativa (mesangiocapilar), com acentuação lobular. Objetivo: Relatar caso de glomerulopatia esquistossomótica que se apresentou 7 anos após tratamento de esquistossomose hepatoesplênica com padrão histológico de glomerulonefrite proliferativa mesangial com depósitos de IgA em mesângio. Clinicamente, evoluiu com diminuição progressiva de proteinúria com bloqueador do receptor de angiotensina (BRA). Método: Foi relatado caso de paciente com 36 anos, parda, com quadro clássico de síndrome nefrótica (proteinúria > 3,5 g/24h, hipoalbuminemia e hipercolesterolemia), no entanto, com histórico de esquistossomose hepatoesplênica há 7 anos e com hipertensão portal. Paciente foi submetida à biópsia renal, que apresentou depósitos de IgA em mesângio, sendo mais intensos que imunoglobulina G (IgG), acompanhados de C1q e C3, com 4/13 glomérulos esclerosados, padrão de lesão renal de glomerulopatia mesangial leve com depósitos de IgA. Paciente iniciou uso de BRA, com melhora progressiva da proteinúria. Conclusão: Pacientes com glomerulopatia por schistosoma não apresentam melhora da progressão da doença com tratamento antiparasitário. Entretanto, o tratamento antiproteinúrico pode retardar a progressão da doença renal crônica terminal.

Intervención para la racionalización del uso de Losartán / Intervention to rationalize use of losartan

Resumen Objetivo: Determinar la frecuencia de prescripción del losartán por encima de 100 mg/día, notificar a los responsables de la atención sanitaria los limitados beneficios y conseguir una reducción en el número de quienes así lo utilizan. Métodos: Estudio cuasiexperimental, antes y después, sin un grupo control, sobre los prescriptores de pacientes con diagnóstico de hipertensión arterial en manejo con losartán entre el 1 de enero de 2010 (41.624 pacientes) y el 31 de diciembre de 2014 (75.126 pacientes). Posteriormente se identificaron las personas que recibieron dosis superiores a 100 mg/día. Se realizaron intervenciones educativas a partir de junio de 2012 y se evaluaron los resultados en términos de proporción de pacientes que dejaron de utilizarlo en estas dosis. Resultados: En el año 2012 se identificaron 7.205 sujetos (12,8% de pacientes con losartán) con más de 100 mg/día, que tras 108 actividades educativas se redujeron a 5.373 en el año 2014 (7,1% de usuarios del antihipertensivo; reducción de 25,4%), a pesar que la población afiliada tuvo un incremento del 29,3% en el período de seguimiento. Tras la intervención se consiguió un ahorro de COP$ 204.293.878 en dos años. Conclusiones: Se logró reducir la prescripción del losartán en dosis superiores a las estimadas como efectivas, lo que implica una reducción en el riesgo de la hiperkalemia y de los costos por dosificación mayor a la recomendada. Es importante reforzar las actividades de educación médica continuada para promover el uso apropiado de los medicamentos.

Abstract Objetive: To determine frequency of prescription of losartan over 100 mg/day, to notify the physicians responsible for the healthcare about the limited benefits and to thus achieve a decrease in the number of individuals taking this dose. Methods: Quasi-experimental study, before and after, without a control group, on prescription factors in patients with a diagnosis of arterial hypertension taking losartan between January 1st 2010 (41,624 patients) and December 31st 2014 (75,126 patients). Afterwards, people receiving doses over 100 mg/day were identified. Educational interventions were conducted starting June 2012, and results were measured in terms of the proportion of patients who stopped taking losartan in these doses. Results: In 2012, 7,205 individuals were identified (12.8% of patients with losartan) with more than 100 mg/day, who after 108 educational activities were reduced to 5,373 by year 2014 (7.1% of patients taking antihypertensive agents; a 25.4% decrease) despite a 29.3% rise in registered participants during the follow-up period. After the intervention, a COP$ 204,293,878 saving was achieved over the course of two years. Conclusions: Prescriptions of losartan in doses higher as what were deemed effective were reduced, which implies a reduction of both the risk of hyperkalemia and the costs due to taking a higher dose than recommended. It is important to reinforce ongoing medical education activities in order to promote appropriate drug consumption.

Inhibición dual de la neprilisina y del receptor de la angiotensina (ARNI): una alternativa en los pacientes con falla cardiaca / Dual angiotensin receptor and neprilysin inhibition (ARNI): an alternative for patients with cardiac failure

La falla cardiaca (FC) es la causa más común de admisión hospitalaria en adultos en el mundo. Además, de su importante prevalencia la FC tiene un alta tasa de mortalidad, se estima que aproximadamente el 50% de los pacientes con FC mueren a los 5 años posterior al egreso hospitalario. Esto ha motivado el desarrollo de nuevas terapias seguras y efectivas para el manejo de esta entidad. El LCZ696 es un inhibidor dual de la neprilisina y del receptor de angiotensina II que demostró en estudios de fase III disminuir el desenlace primario de muerte cardiovascular y hospitalización por empeoramiento de la FC y muerte global. Probablemente el LCZ696 se convertirá en la piedra angular del manejo en pacientes con FC con fracción de eyección deprimida.

Cardiac failure (CF) is the most common cause of hospital admission in adults all over the world. In addition to its important prevalence, CF presents a high mortality rate. It is estimated that approximately 59% of patients with CF die within 5 years after the admission. This has been the motivation for the development of new, safe and effective therapies aimed at the management of this disease. LCZ696 is an angiotensin II receptor-neprilysin inhibitor; phase III studies have shown it decreases the primary outcome of cardiovascular death and admission due to worsening of the CF and global death. LCZ696 could probably become the cornerstone of the management of patients with CF with depressed ejection fraction.

Human fetal malformations associated with the use of an angiotensin II receptor antagonist: Case Report / Malformações fetais associadas ao uso de antagonista dos receptores de angiotensina II: Relato de Caso

Introduction: The potential risks related to drug exposure during pregnancy represent a vast chapter in modern obstetrics and data regarding the safety of antihypertensive drugs during pregnancy are relatively scarce. Case report: A 37-year-old patient discovered her fifth pregnancy at our hospital after 26 weeks and 4 days of gestation. She reported a history of hypertension and was currently being treated with Losartan. Hospitalization was recommended for the patient and further evaluation of fetal vitality was performed. On the fourth day an ultrasound was performed, resulting in a severe oligohydramnios, fetal centralization and abnormal ductus venosus. After 36 hours, the newborn died. Pathologic evaluation: At autopsy, the skullcap had large fontanels and deficient ossification. The kidneys were slightly enlarged. A microscopic examination detected underdevelopment of the tubules and the presence of some dilated lumens. Immunohistochemical detection of epithelial membrane antigen was positive. Immunoreactivity of CD 15 was also assayed to characterize the proximal tubules, and lumen collapse was observed in some regions. Discussion: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor antagonists (ARAs) are among the most widely prescribed drugs for hypertension. They are often used by hypertensive women who are considering become pregnant. While their fetal toxicity in the second or third trimesters has been documented, their teratogenic effect during the first trimester has only recently been demonstrated. Conclusion: Constant awareness by physicians and patients should be encouraged, particularly in regard to the prescription of antihypertensive drugs in women of childbearing age who are or intend to become pregnant. .

Introdução: Os riscos relacionados à exposição de drogas durante a gestação representam um vasto capítulo na obstetrícia moderna e dados sobre a segurança de drogas anti-hipertensivas são relativamente escassos. Relato do caso: Paciente de 37 anos, hipertensa crônica, descobriu a gravidez com 26 semanas e 4 dias de gestação. Estava em uso regular de Losartana. Durante avaliação fetal ultrassonográfica, foi relatada a presença de grave oligoâmnio associado ao quadro de centralização fetal com alteração de ducto venoso, e, após 36 horas, verificou-se óbito neonatal. Necrópsia: Observou-se calota craniana com fontanelas amplas e ossificação deficiente. Rins levemente aumentados de volume e, à microscopia, hipodesenvolvimento de túbulos com presença de lúmen dilatado. Imunohistoquímica com expressão em túbulos distais de antígeno epitelial de membrana. Imunoperoxidade com expressão em túbulos proximais de CD 15 em células epiteliais e colapso de alguns lúmens fora observado. Discussão: Inibidores da conversão de angiotensina e antagonistas de receptor de angiotensina estão entre as drogas mais prescritas para hipertensão. Estas drogas são frequentemente prescritas para mulheres em idade fértil e que pretendem engravidar. Enquanto a toxicidade fetal destas, nos segundo e terceiro trimestres, já é conhecida, seus efeitos durante o primeiro trimestre foi apenas recentemente demostrado. Conclusão: A conscientização por parte de médicos e pacientes deve ser realizada de rotina, principalmente no que diz respeito à prescrição e utilização de drogas potencialmente teratogênicas ou fetotóxicas. Este cuidado deve ser redobrado para pacientes que estão ...

Tratamiento de la hipertensión arterial en presencia de enfermedad renal crónica / Treatment of hypertension in CKD patient

La mejoría en la sobrevida también ofrece una mayor posibilidad de padecer enfermedades crónicas degenerativas entre las que destacan la diabetes mellitus y la hipertensión arterial (HTA). La enfermedad renal crónica (ERC) actualmente constituye una pandemia y la HTA está presente en prácticamente todos los estadios de la ERC, el descontrol hipertensivo y la necesidad de ingerir más fármacos para obtener valores tensionales adecuados se hace más evidente a medida que progresa el estadio de la enfermedad. El enfermo renal presenta HTA de difícil control, en él se conjugan la activación adrenérgica, activación del sistema nervioso renina angiotensina aldosterona, la retención hídrica y mecanismos vasculares. El tratamiento antihipertensivo vigente en presencia de daño renal se enfoca a disminuir las cifras de presión arterial, disminuir el riesgo cardiovascular y brindar renoprotección, los antagonistas de receptores de angiotensina han demostrado ser la terapia farmacológica de elección independientemente de la enfermedad subyacente y del grado de proteinuria, la combinación con IECA no resulta en un mayor beneficio y si en efectos adversos graves como hipercalemia, inclusive potencialmente letales que incluyen síndrome de muerte súbita. El tratamiento de la HTA en la ERC deberá ir más allá de sólo la reducción de cifras de presión arterial, al considerar que en estos pacientes el riesgo cardiovascular se encuentra muy incrementado y el enlentecimiento de la progresión del daño renal es imperativo.

Improvement in survival involves a greater possibility of developing chronic degenerative diseases among which diabetes mellitus and hypertension stand out. Chronic kidney disease (CKD) is now a pandemic and hypertension is present in virtually all stages of CKD, the uncontrolled hypertension and the need to ingest more drugs to have adequate blood pressure values becomes more evident as disease stage progresses. Renal patients have high blood pressure difficult to control, and combine adrenergic activation, activation of the renin angiotensin aldosterone nervous system, water retention and vascular mechanisms. Current antihyperten-sive treatment when kidney damage is present focuses on reducing blood pressure, reducing cardiovascular risk and providing renoprotection; angiotensin receptor antagonists have been proven to be the pharmacological therapy of choice regardless of the underlying disease and the degree of proteinuria, the combination with ACEI does not result in a greater benefit but do produce serious adverse effects such as hyperkalemia, and even potentially lethal damage, including sudden death syndrome. Treatment of hypertension in CKD must go beyond just reducing blood pressure, considering that cardiovascular risk is greatly increased in these patients and that slowing the progression of kidney damage is imperative.

Asociación entre los polimorfismos de los genes de la enzima convertidora de angiotensina y los receptores AT1R y AT2R y el cáncer de mama: Estudio de casos y controles / The association between the angiotensin converter enzyme (ACE), AT1R and AT2R receptor gene polymorphisms and breast cancer: a case control

Introducción: el cáncer de mama es el segundo casos y 50 controles y se genotipificaron los tipo de cáncer más común y la quinta causa de muerte por cáncer a nivel mundial. Un candidado potencial para la etapa de quimio-prevención es el sistema renina-angiotensina en sus componentes: la enzima convertidora de la angiotensina (ECA), y los receptores de angiotensina II tipo 1 y 2 (ATIR y AT2R).Objetivo: establecer la asociación entre los de cáncer de mama en nuestra población de polimorfismos de los genes de la ECA, los estudio. receptores AT1R y AT2R y el cáncer de mama.Materiales y métodos: se incluyeron 50 casos y 50 controles y se genotipificaron los polimorfismos genéticos Resultados: el genotipo II presentó mayor frecuencia en los controles que en los casos, mientras que el genotipo ID fue más frecuente en los casos, sin diferencias estadísticamente significativas. No se encontró ningún tipo de efecto aditivo de los genotipos y el riesgo de cáncer de mama en nuestra población de estudio. Conclusiones: se ha descrito que la susceptibilidad al cáncer de mama es un fenómeno complejo, en el cual múltiples genes pueden desempeñar un papel importante. Para el caso de esta población, los polimorfismos evaluados no se asocian al cáncer de mama. Se requieren más estudios, con mayor fuerza metodológica sobre este tema, antes de proponer cambios en la práctica clínica.

Introduction: breast cancer is the second most common type of cancer and the fifth cause of death due to cancer around the world. The components of the renin-angiotensin system are potential candidates for chemoprevention therapy: the angiotensin converter enzyme (ACE) and type 1 and 2 angiotensin II receptors (AT1R and AT2R). Objective: establishing an association between ACE gene polymorphisms, AT1R and AT2R receptors and breast cancer. Materials and methods: 50 cases and 50 controls were included and their genetic polymorphisms genotyped. Results: genotype II occurred with greater frequency in controls than in the cases whilst the ID genotype had greater frequency in the cases (without having statistically significant differences). No type of additive effect of genotypes was found with the risk of breast cancer in the population being studied. Conclusions: susceptibility to breast cancer has been described as being a complex phenomenon in which many genes may play an important role. In the case of the population studied here, the polymorphisms evaluated were not associated with breast cancer. Further studies having greater methodological rigor regarding this topic are required before changes in clinical practice can be proposed.

The effect of anti-hypertensive drugs on the obstructive pancreatitis in rats / Efeitos de fármacos anti-hipertensivos sobre pancreatite obstrutiva em ratos

PURPOSE: To investigate the effect of ACE inhibitor, lisinopril and AT1 blocker, losartan, on the obstructive pancreatitis in rat. METHODS: Acute pancreatitis in rats (n=21) was induced for a common hepatic duct were ligated proximal to its entry into the pancreas and the common bile - pancreatic duct were also ligated near its junction with the duodenum, under ether anesthesia, after which the abdomen were closed. The animals was divided in tree groups, being two treated and control group. The animals was treated with Losartan and Lisinopril at the dose of 10µg/Kg body weight per day, i.p., in a proportional volume, for five days, before and after treatement. RESULTS: The inflammation, collagen deposition in the pancreas of treated animals were smaller, suggesting that the use of antihypertensive agents interfered positively in the depletion of the injury of the pancreas. Scythe showed a correlation between activity of pancreatic stellate cells (PSCs) lower in treated animals when compared to control. CONCLUSION: The pancreatic stellate cells strength are involved in collagen production during acute pancreatitis and why antihypertensive drugs such as lisinopril and losartan may possibly have beneficial effects in reducing pancreatic fibrosis in models of experimental obstructive pancreatitis.

OBJETIVO: Investigar o efeito de um inibidor da ECA, lisinopril e bloqueador AT1, losartan, a pancreatite obstrutiva em ratos. MÉTODOS: Pancreatite aguda em ratos (n = 21) foi induzida por um ducto hepático comum foram ligados proximal à sua entrada no pâncreas e da bílis comum - ducto pancreático também foram ligados perto de sua junção com o duodeno, sob anestesia com éter, após o que abdome foram fechadas. Os animais foram divididos em três grupos, sendo dois tratados eo grupo controle. Os animais foram tratados com lisinopril e losartan na dose de 10µg/Kg de peso corporal por dia, IP, em um volume proporcional, por cinco dias, antes e depois do tratamento com. RESULTADOS: A inflamação, deposição de colágeno no pâncreas de animais tratados foram menores, sugerindo que o uso de agentes anti-hipertensivos interferiram positivamente na diminuição da lesão do pâncreas. Este estudo mostrou uma correlação entre a atividade das células pancreáticas estreladas (CSP) menor nos animais tratados quando comparados ao control. CONCLUSÃO: A força das células pancreáticas estreladas está envolvida na produção de colágeno durante a pancreatite aguda e por medicamentos anti-hipertensivos, tais como lisinopril e losartan pode eventualmente ter efeitos benéficos na redução da fibrose do pâncreas em modelos experimentais de pancreatite obstrutiva.

Los antagonistas de los receptores de la angiotensina II a la luz de los estudios de mayor impacto / Los antagonistas de los receptores de la angiotensina II a la luz de los estudios de mayor impacto

Introducción: Los antagonistas de los receptores de la angiotensina II constituyen un grupo reciente de fármacos para el tratamiento de la hipertensión arterial (HTA), su utilidad se ha extendido además al manejo de la Insuficiencia cardiaca, la nefroproteccion y el infarto agudo de miocardio. Farmacología: Actúan sobre el sistema renina-angiotensina-aldosterona aunque de diferente forma, bloqueando la unión de la angiotensina II a los receptores tipo 1 de la angiotensina II presentes en numerosos tejidos (tejido muscular liso, glándula adrenal y miocardio) y, como consecuencia, inhiben su efecto vasopresor y liberador de aldosterona. Conclusiones: En la hipertensión arterial. Son la alternativa a los inhibidores de la enzima conversora de la angiotensina (IECA) cuando sea necesario utilizar un antihipertensivo del eje renina-angiotensina y el paciente no pueda o no deba utilizar un fármaco de dicho subgrupo. Como nefroprotectores. Si bien los Antagonistas de los receptores de la Angiotensina (ARA II) han disminuido los niveles de proteinuria en pacientes renales siguen siendo una alternativa a los IECA. En la insuficiencia cardiaca. Los IECA son el tratamiento inicial, mientras que los ARA II pueden ser útiles en pacientes que no los toleren. En el post infarto agudo de miocardio. Los IECA siguen siendo el tratamiento de elección y los ARA II la alternativa cuando el paciente no tolere los IECA.

Introduction: Angiotensin-receptor blockers constitute a recent group of medicaments for the treatment in hypertension, its usefulness has spread in addition to the managing of the cardiac Insufficiency, renal protection and acute myocardial infarction. Pharmacology: Alter renin-angiotensin-aldosterone system though of different form, blocking the unión of angiotensin II to its receptors (type 1) in numerous organs (muscle, adrenal gland and myocardium) and, its consequence, disable its vasopresor effect and aldosterone liberating. Conclusions: In hypertension. Angiotensin-receptor blockers are alternative to angiotensine-converting-enzime inhibitors when it is necessary to use these antihypertensives and the patient could not or should not use a medicament of the above mentioned subgroup. In renal protection. Though Angiotensin-receptor blockers have diminished the levels of proteinuria in renalpatients continued being an alternative to angiotensine-converting-enzime inhibitors. In cardiac insufficiency. Angiotensine-converting-enzime inhibitors are initial treatment, whereas Angiotensin-receptor blockers can be usefulin patients who do not tolerate them. In post-acute myocardial infarction. Angiotensine-converting-enzime inhibitors continued being treatment of choice and the alternative when patients do not tolerate these medicaments.

Triagem de mutações nos receptores de Angiotensina II, AGTR1 e AGTR2 e avaliação dos polimorfismos C573T e A1166C do gene AGTR1 em pacientes com adrenarca precoce idiopática / Mutation screening in Angiotensin II receptors, AGTR1 and AGTR2, and evaluation of AGTR1 polymorphisms C573T and A1166C in patients with premature adrenarche / Mutation screening in Angiotensin II receptors, AGTR1 and AGTR2, and evaluation of AGTR1 polymorphisms C573T and A1166C in patients with premature adrenarche

Pubarca precoce é o aparecimento de pêlos pubianos antes dos 8 anos em meninas e 9 anos em meninos, sendo sua etiologia mais freqüente a adrenarca precoce idiopática, a longo prazo, associada à síndrome metabólica. Dentre os fatores envolvidos na gênese da adrenarca precoce podemos citar a Angiotensina II (Ang II), a qual promove proliferação celular e esteroidogênese, podendo agir através de dois receptores, o tipo 1 (AT1) e o tipo 2 (AT2). Com o intuito de estudar mutações dos genes dos receptores da AngII, foram avaliadas 50 crianças com diagnóstico de adrenarca precoce idiopática e comparadas ao grupo controle de indivíduos normais. Não foram detectadas mutações dos genes AGTR1 e AGTR2, contudo dois polimorfismos foram identificados no gene AGTR1: o polimorfismo C573T (localizado no exon 5) e o A1166C (na região 3' não codificadora). A freqüência do alelo polimórfico T573 foi de 35 por cento nos pacientes e 38 por cento nos controles. O alelo polimórfico C1166 esteve presente em 24 por cento dos pacientes e em 26 por cento dos controles. Não houve diferença significante entre os grupos, assim como não houve correlação entre a freqüência dos polimorfismos C573T e A1166C e as variáveis clínicas e laboratoriais dos pacientes, ou com sua história familial de síndrome metabólica.

Precocious pubarche is the appearance of pubic hair before the age of 8 years in girls and 9 years in boys. The most frequent etiology is idiopathic precocious adrenarche, suggested, after long-term follow-up, to be associated with metabolic syndrome. One of the factors involved in the genesis of precocious adrenarche is Angiotensin II (Ang II), which promotes cell proliferation and steroidogenesis through type 1 (AT1) and type 2 (AT2) receptors. In order to study Ang II receptors mutations, 50 children with idiopathic precocious adrenarche were evaluated and compared to a control group of normal individuals. Mutations were not detected in the AGTR1 and AGTR2 genes; however, two polymorphisms were identified in the AGTR1 gene: the C573T (exon 5) and the A1166C (3' untranslated region). The polymorphic allele T573 was found in 35 percent of the patients and 38 percent of controls. The polymorphic allele C1166 was present in 24 percent of the patients and 26 percent of controls. There was no statistical difference between groups. There was also no correlation between the polymorphisms and clinical and laboratory findings, as well as their family history of metabolic syndrome.

Antagonistas de los receptores de angiotensina II

Se propuso revisar los nuevos conocimientos sobre los receptores de la angiotensina II y las implicaciones clínicas y terapéuticas derivadas de su bloqueo farmacológico. Se destacó la reconocida importancia del sistema renina-angiotensina en la regulación cardiovascular y renal y se explicó que sus efectos están medidos por la acción de la AII sobre sus receptores (tipo 1 y tipo 2). Se concluyó que los recientes avances en el control farmacológico de ese sistema, especialmente por la aparición de nuevos antagonistas de los receptores de la AII activos por vía oral, como el losartán, pueden ser de extraordinaria eficacia en el tratamiento de la hipertensión arterial, insuficiencia cardíaca y en evitar la progresión de la insuficiencia renal crónica.

The purpose of this paper was to review the new knowledge about angiotensin II receptors as well as the clinical and therapeutic implications resulting from their pharmacological block. It was stressed the great importance of the renin-angiotensin system in the cardiovascular and renal regulation and it was also explained that its effects are measured by the action of AII on its receptors (type 1 and type 2). It was concluded that the recent advances achieved in the pharmacological control of that system, specially due to the appearance of new orally active angiotensin II receptor antagonists, such as losartan, may be extraordinarily efficient in the treatment of arterial hypertension and heart failure, and may prevent the progression of chronic kidney failure.