Bloqueo del eje renina angiontensina aldosterona (RAAS) en la enfermedad renal diabética. Más allá del control de la hipertensión arterial / Renin angiotensin aldosterone system (RAAS) and its suppression in diabetic kidney disease. Control of arterial hypertension and beyond

La enfermedad renal diabética (ERD) es una comorbilidad con alta prevalencia a nivel mundial, siendo una de las complicaciones más frecuentes de la diabetes mellitus (DM). La ERD se relaciona con complicaciones cardiovasculares y progresión de la enfermedad renal crónica (ERC), por ello la identificación de factores modificables, como el control de la presión arterial, es uno de los pilares más importantes en el manejo integral. En esta revisión hacemos un recorrido sobre el papel de la hipertensión y el bloqueo del eje renina angiotensina aldosterona (RAAS) en el curso de la ERD y las estrategias terapéuticas orientadas a la reducción de la presión arterial (PA), el bloqueo RAAS y el impacto en resultados renales y cardiovasculares. El objetivo de este artículo es hacer una revisión de las intervenciones más importantes que actúan bloqueando el eje renina angiotensina aldosterona (RAAS) y determinar si estas medidas en los pacientes con ERD, solo tienen impacto en el control de la presión arterial o si también son estrategias de nefro y cardio-protección. Conclusión: La ERD es una de las complicaciones más frecuentes de la diabetes mellitus (DM). El control de la PA sigue siendo un pilar fundamental para lograr estos objetivos. Los bloqueadores del RAAS (iECAS y BRAs) son los antihipertensivos de elección con efecto terapéutico por el bloqueo RAAS y esto les permite tener además del control de la PA, efectos nefroprotectores y cardioprotectores importantes en pacientes con ERD, sobre todo cuando hay la presencia de albuminuria. Evaluamos que además de los inhibidores de la enzima convertidora de angiotensina (iECAs) y los bloqueadores del receptor de angiotensina (BRAs), vienen tomando importancia los antagonistas selectivos del receptor mineralocorticoide (ARM) como Finerenona.

Diabetic kidney disease (DKD) is a comorbidity with a high worldwide prevalence, and one of the most frequent complications of diabetes mellitus (DM). CKD is related to cardiovascular complications and the progression of chronic kidney disease (CKD), therefore the identification of modifiable factors, such as blood pressure control, is one of the most important pillars in comprehensive management. In this review, we will analyze the role of hypertension and the renin-angiotensin-aldosterone system (RAAS) and its suppression in the course of CKD, and therapeutic strategies aimed at reducing blood pressure (BP), RAAS blockade, and the impact on renal and cardiovascular outcomes. The objective of this article is to review the most important interventions that act by blocking the renin-angiotensin-aldosterone system (RAAS) and to determine if these measures in patients with CKD only have an impact on blood pressure control or if they are also nephron and cardio-protective strategies. Conclusion: DKD is one of the most frequent complications of diabetes mellitus (DM). BP control continues to be a fundamental pillar to achieve these objectives. RAAS blockers (iECAS and ARBs) are the first-line antihypertensive with a therapeutic effect due to RAAS blockade and this allows them to have, in addition to BP control, important nephroprotective and cardioprotective effects in patients with CKD, especially when there is albuminuria. We evaluated that in addition to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), selective mineralocorticoid receptor antagonists (MRA) such as Finerenone are gaining importance.

Association between angiotensinogen M235T gene polymorphism and risk of hypertension: A case control study among Ethiopian patients

Background: Hypertension is a major public health problem in both developing and developed nations because it is highly prevalent and is associated with complications. Numerous enviromnental and genetic variables are linked to the occurrence of the disease. It may be influenced by the renin-angiotensin-aldosterone system, M'hich preserves bodily homeostasis. The angiotensinogen gene 11235T polymorphisms that has an effect on the activity of the renin-angiotensin-aldosterone system are related to the high hvpertension risk. The aim of this study was to find out the association between angiotensinogen Nf235T gene polymorphism and the risk of developing hypertenMon. Methods: A total of 306 samples - 153 patients Il'ith hvpertension and 153 age- and ser-matched healthy controls were selected using a simple random sampling technique. Clinical and biochemical variables were measured to assess the associated riskfactors. Blood samples from the patients and matched controls were used to isolate deoxyribonucleic acid. The AGT 11235T genotypes u:ere identified using polymerase chain reaction and analyzed by agarose gel electrophoresis. Logistic regression with a 95% confidence interval (CI) was employed to assess the risk correlations ofAGT gene M235Tpolymorphisms with hypertension. Results: Our analysis showed that the AGT-TT genotype (odds ratio [OR] = 3.11, 95% CL = 1.67­5.79, P< 0.001) and T allele (OR = 2.18, 95% CL = 1.56­3.04, P< 0.001) are considerably higher in hypertensive patients than in healthy controls. Our study also identified the clinical risk factors for hypertension, such as, total cholesterol, triglycerol, low density lipoprotein-cholesterol, and high density lipoprotein-cholesterol Inels, which were significantly higher in patients compared to controls (P< 0.001). Conclusion: The A GT M235T genes of the TT genotype and the T allele are associated with an increased risk of hypertension among the Ethiopian patients. A population-based epidemiological study is needed corroborate the association between AGT and HTN

Kidney xenotransplantation: status quo and development trend of physiological research / 器官移植

Organ transplantation is the most effective treatment for all categories of end-stage organ diseases. To resolve the shortage of donors in organ transplantation, widespread attention has been diverted to xenotransplantation. At present, clinicians mainly highlight the problems related to xenotransplantation rejection and viral infection. The physiology of xenotransplantation has been rarely studied. Kidney performs endocrine function by producing erythropoietin (EPO), renin and activating vitamin D. Although these pathways are usually well preserved in allogeneic transplantation, species-specific differences, especially those between pigs and non-human primates, may still affect the physiological function of transplant organs. In this article, the changes of EPO, renin-angiotensin-aldosterone system (RAAS) and active vitamin D3 of pig and human after xenotransplantation were illustrated, aiming to provide reference for subclinical research of xenotransplantation.

Interactions amongst inflammation, renin-angiotensin-aldosterone and kallikrein-kinin systems: suggestive approaches for COVID-19 therapy

Coronavirus disease 2019 (COVID-19) is a rapid-spread infectious disease caused by the SARS-CoV-2 virus, which can culminate in the renin-angiotensin-aldosterone (RAAS) and kallikrein-kinin (KKS) systems imbalance, and in serious consequences for infected patients. This scoping review of published research exploring the RAAS and KKS was undertaken in order to trace the history of the discovery of both systems and their multiple interactions, discuss some aspects of the viral-cell interaction, including inflammation and the system imbalance triggered by SARS-CoV-2 infection, and their consequent disorders. Furthermore, we correlate the effects of continued use of the RAAS blockers in chronic diseases therapies with the virulence and physiopathology of COVID-19. We also approach the RAAS and KKS-related proposed potential therapies for treatment of COVID-19. In this way, we reinforce the importance of exploring both systems and the application of their components or their blockers in the treatment of coronavirus disease.(AU)

Interactions amongst inflammation, renin-angiotensin-aldosterone and kallikrein-kinin systems: suggestive approaches for COVID-19 therapy

Abstract Coronavirus disease 2019 (COVID-19) is a rapid-spread infectious disease caused by the SARS-CoV-2 virus, which can culminate in the renin-angiotensin-aldosterone (RAAS) and kallikrein-kinin (KKS) systems imbalance, and in serious consequences for infected patients. This scoping review of published research exploring the RAAS and KKS was undertaken in order to trace the history of the discovery of both systems and their multiple interactions, discuss some aspects of the viral-cell interaction, including inflammation and the system imbalance triggered by SARS-CoV-2 infection, and their consequent disorders. Furthermore, we correlate the effects of continued use of the RAAS blockers in chronic diseases therapies with the virulence and physiopathology of COVID-19. We also approach the RAAS and KKS-related proposed potential therapies for treatment of COVID-19. In this way, we reinforce the importance of exploring both systems and the application of their components or their blockers in the treatment of coronavirus disease.

Changes of the renin-angiotensin-aldosterone system in children with orthostatic intolerance and their significance / 中华实用儿科临床杂志

Orthostatic intolerance (OI) is the most common type of autonomic mediated syncope in children.Children with OI tend to show intolerance to the postural changes and long-term standing, thus often presenting with such clinical symptoms as dizziness, headache, blackness, and even sudden fainting.Although there is no organic lesion from OI, it can still exert serious impacts on the mental health of children.Therefore, it is of great significance to provide active and effective treatment for children with OI.There is some understanding of OI, but it is still unclear about its pathogenesis, which is believed to be related to dysautonomia and abnormal neurohumoral regulation.In this paper, the focus would be placed on the changes of renin-angiotensin-aldosterone system (RAAS) in neurohumoral regulation and their significance, and an exploration would be performed on the impacts of related treatment on RAAS in children with OI.

Vitamina d, sus acciones "no clásicas" y su utilidad en la pandemia del covid-19 / Vitamin d, its "non-classic" actions and it utility in the covid-19 pandemic

RESUMEN El descubrimiento de que la síntesis de 1,25 vitamina D no fue solo renal, la enzima 1 alfa hidroxilasa se encuentra en numerosos tejidos del organismo, además de la evidencia de que la asociación entre el déficit de vitamina D y la presencia de enfermedades no óseas (cáncer, esclerosis múltiple, enfermedades autoinmunes, etc.) nos ofrece la posibilidad de intentar prevenir estas afecciones. Los estudios de suplementación contra placebo no han dado resultados positivos para algunas afecciones, aunque algunos de esos trials se realizaron en población "suficiente" y no "deficiente" de vitamina D. Sin embargo, otros metaanálisis han demostrado prevención en los grupos suplementados con déficit para algunas patologías (infecciones respiratorias, prediabetes). Además, existe evidencia de efecto antiviral de la misma. La acción antiinfecciosa e inmunomoduladora que ejerce y su efecto sobre el sistema renina angiotensina, estimulando la enzima convertidora de angiotensina 2 (que es el receptor virus del SARS-CoV), permiten sospechar, actualmente, que con niveles elevados podría ser más difícil, o menos grave, la infección por COVID-19. La suplementación con vitamina D es conveniente para prevenir enfermedades en sujetos con déficit, pero en medio de la grave pandemia 2020 administrarla, aún sin tener un dosaje previo en las poblaciones de mayor riesgo, podría disminuir la chance de esta enfermedad.

ABSTRACT The discovery that the synthesis of 1-25-vitamin D is not only renal and that the enzyme 1 alpha hydroxylase is found in numerous tissues of the body, together with the evidence of the association between vitamin D deficiency and the presence of non-bone diseases (cancer, multiple sclerosis, autoimmune diseases, etc.), gives us the possibility of trying to prevent these conditions. Placebo-controlled supplementation studies have not provided positive results for certain conditions, but some of these trials have been carried out on populations with "sufficient" and not "deficient" vitamin D levels. However, other meta-analyses have shown prevention of some conditions (respiratory infections, prediabetes) in groups of patients with deficiencies who were given supplements. There is also evidence of antiviral effect of vitamin D. Its anti-infective and immunomodulatory action and its effect upon the renin-angiotensin system, stimulating the angiotensin-converting enzyme 2 (the SARS-CoV virus receptor), nowadays allow us to think that, in high levels, COVID-19 infection could be less likely or serious. Vitamin D supplementation is adequate for preventing diseases in patients with deficiencies; administering vitamin D within the 2020 pandemic, even without having tested it in high-risk populations, could diminish the incidence of this disease.

COVID-19 e hipertensión arterial: ¿existe evidencia para suspender antagonistas del sistema renina-angiotensina-aldosterona? / COVID-19 and arterial hypertension: is there evidence to suspend renin-angiotensin-aldosteronesystem blockade?

Resumen El nuevo coronavirus SARS-CoV-2, causante de la enfermedad COVID-19, presenta una alta mortalidad en pacientes con enfermedades cardiovasculares, diabetes e hipertensión, trastornos que comparten la fisiopatología subyacente relacionada con el sistema renina-angiotensina (RAS). El SARS-CoV-2 utiliza la proteína de la membrana angiotensina I y convierte a la enzima convertidora de angiotensina tipo 2 (ACE2) en un receptor de entrada celular; por tanto, el RAS, regulado por ACE y ACE2, puede verse alterado en pacientes con COVID-19. Sin embargo, aún no es claro si el uso de fármacos antihipertensivos inhibidores de la ACE2 y bloqueadores del receptor de angiotensina II podría potencializar el daño ocasionado por el virus o contrarrestar su efecto, sobre todo a nivel pulmonar. El desafío se ve agravado por la información exagerada publicada en diferentes revistas científicas, la cual podría llevar a acciones inapropiadas, por lo que es importante diferenciar rápidamente la verdadera epidemia de hipótesis falsas, que podría llevar a conductas medicas potencialmente dañinas.

Abstract The new coronavirus SARS-CoV-2, which causes the disease COVID-19, has a high mortality in patients with cardiovascular diseases, diabetes and hypertension, disorders that share the underlying pathophysiology related to the renin-angiotensin system (RAS). SARS-CoV-2 uses the membrane protein angiotensin I and converts angiotensin converting enzyme type 2 (ACE2) into a cellular entry receptor, therefore, RAS, regulated by ACE and ACE2, can be altered in COVID-19 patients. However, it is not yet clear whether the use of antihypertensive drugs ACE2 inhibitors and angiotensin II receptor blockers could potentiate the damage caused by the virus or counteract its effect, especially in the lungs. The challenge is compounded by the exaggerated information published in different scientific journals, which could lead to inappropriate actions, so it is important to quickly differentiate the true epidemic from false hypotheses, which could lead to potentially harmful medical behaviors.

Enfermedad cardiovascular, oncológica y reumatológica, su comportamiento en pacientes COVID-19: Factores pronósticos, complicaciones y tratamiento

La infección por SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) puede presentar manifestaciones propias, pero también, puede exacerbar las de enfermedades preexistentes o provocar manifestaciones que simulen dichas patologías. Las enfermedades cardiovasculares, neoplásicas o reumatológicas son ejemplos de ello. Este tipo de patologías comparten factores de riesgo de mal pronóstico y de muerte por la infección, la posibilidad de desarrollar complicaciones a largo plazo, e implican un desafío al momento de instaurar medidas de seguimiento y tratamiento con requerimiento de valoración multidisciplinaria. Por ello, nuestro objetivo fue plantear las dificultades en el seguimiento a corto y largo plazo de este tipo de pacientes y evaluar cómo la pandemia afecta su tratamiento. La pandemia ha cambiado la práctica médica habitual, promoviendo nuevas formas de seguimiento de los pacientes, como la telemedicina, imponiendo jerarquizar la necesidad de atención y procedimientos presenciales, obligando a reasignar las partidas presupuestarias para poder hacer frente a la misma, con consecuencias que probablemente habrá que analizar a largo plazo.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection clinical course can present its own manifestations, but it can also exacerbate those of pre-existing diseases or cause manifestations that simulate said pathologies. Cardiovascular, cancer or rheumatological diseases are examples of this. These types of pathologies share risk factors for poor prognosis and death due to infection, the possibility of developing long-term complications, and they imply a challenge when establishing follow-up and treatment measures requiring multidisciplinary assessment. Therefore, our objective was to raise the difficulties in the short and long-term follow-up of this type of patients and to evaluate how the pandemic affects their treatment. The pandemic has changed the usual medical practice, promoting new forms of patient follow-up, such as telemedicine, imposing a hierarchy of the need for face-to-face care and procedures, forcing budget items to be reallocated to be able to deal with it, with consequences that are likely to it will have to be analyzed in the long term.

A infecção por SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pode apresentar manifestações próprias, mas também pode exacerbar aquelas de doenças pré-existentes ou causar manifestações que simulam essas patologias. Doenças cardiovasculares, neoplásicas ou reumatológicas são exemplos disso. Esses tipos de patologias compartilham fatores de risco para mau prognóstico e óbito por infecção, possibilidade de desenvolvimento de complicações em longo prazo, e representam um desafio no estabelecimento de medidas de acompanhamento e tratamento que requerem avaliação multidisciplinar. Portanto, nosso objetivo foi levantar as dificuldades no acompanhamento a curto e longo prazo desse tipo de paciente e avaliar como a pandemia afeta seu tratamento. A pandemia alterou a prática médica usual, promovendo novas formas de acompanhamento do paciente, como a telemedicina, impondo uma hierarquia da necessidade de atendimento e procedimentos presenciais, obrigando a realocação de itens orçamentários para poderem lidar com ela, com consequências que provavelmente terá que ser analisado a longo prazo.

IECA E BRA: EXISTEM DIFERENÇAS? / ACE AND ARBS: ARE THERE DIFFERENCES?

O bloqueio do sistema renina angiotensina aldosterona é uma estratégia fundamental no tratamento e prevenção da doença cardiovascular. No contexto da hipertensão arterial (HAS), os inibidores da enzima conversora de angiotensina e os bloqueadores dos receptores de angiotensina compõem, juntamente com os diuréticos tiazídicos e os antagonistas dos canais de cálcio; o tripé fundamental no tratamento farmacológico da HAS. Adicionalmente, estas classes de fármacos são comumente usadas em pacientes com insuficiência cardíaca, doença arterial coronariana, diabetes e doença renal crônica. Neste ponto de vista os autores discutem as semelhanças e diferenças entre inibidores da enzima conversora de angiotensina e os bloqueadores dos receptores de angiotensina, demonstrando que, à luz dos conhecimentos disponíveis atualmente na literatura, é possível reconhecer que essas duas classes de fármacos são diferentes e têm efeitos clínicos distintos

Blockade of the renin angiotensin aldosterone system is a fundamental strategy in the treatment and prevention of cardiovascular disease. In the context of arterial hypertension, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers make up, along with thiazide diuretics and calcium channel antagonists; the fundamental tripod in the pharmacological treatment of SAH. In addition, these classes of drugs are commonly used in patients with heart failure, coronary artery disease, diabetes and chronic kidney disease. From this point of view, the authors discuss the similarities and differences between angiotensinconverting enzyme inhibitors and angiotensin receptor blockers, demonstrating that in light of the knowledge currently available in the literature, it is possible to recognize that these two classes of drugs are different and have distinct clinical effects

COVID-19: relación entre enzima convertidora de angiotensina 2, sistema cardiovascular y respuesta inmune del huésped

La enfermedad por coronavirus 2019 (COVID-19) provoca el síndrome respiratorio agudo severo por coronavirus 2 (SARS-CoV-2), pudiendo ser particularmente perjudicial para los pacientes con enfermedad cardiovascular (ECV) subyacente, y siendo una causa de morbilidad y mortalidad significativas en todo el mundo. El virus infecta las células huésped a través de los receptores de la enzima convertidora de la angiotensina 2 (ECA2) y su internalización del complejo en dicha célula. ACE2 es un componente enzimático clave del sistema renina-angiotensina-aldosterona (SRAA), degradando angiotensina (Ang) II, un péptido con múltiples acciones que promueven ECV, y generando Ang-(1-7), que antagoniza los efectos de Ang II. Además, la evidencia experimental sugiere que el bloqueo de SRAA por los inhibidores de la ECA y los antagonistas de los receptores de tipo 1 de Ang II, aumentan la ECA2 que, en parte, contribuye al beneficio de estos pacientes. Este virus lleva a una neumopatía, al tiempo que causa lesiones agudas de miocardio y daño crónico al sistema cardiovascular. Esta lesión miocárdica se presenta en la fase más severa de COVID-19; pero aún, el mecanismo fisiopatológico de la lesión no fue esclarecido. Por lo tanto, se debe prestar especial atención a la protección cardiovascular durante el tratamiento para COVID-19. El síndrome de dificultad respiratoria aguda (SDRA) es una enfermedad clínica de alta mortalidad, y ACE2 tiene un efecto protector sobre este tipo de lesión pulmonar aguda. La investigación actual muestra que el mal pronóstico de los pacientes con COVID-19 está relacionado con factores como género masculino, la edad >60 años, las enfermedades subyacentes: hipertensión, diabetes, ECV, SDRA secundario y otros factores relevantes. Si bien los datos son limitados, los posibles mecanismos de lesión miocárdica incluyen la entrada viral directa a través del receptor de membrana de la ECA2 y la toxicidad en las células huésped, la lesión de miocitos relacionada con la hipoxia y el síndrome de liberación de citoquinas mediado por el sistema inmune, necesitándose más estudios para esclarecer el mecanismo de cardiotoxicidad y su prevención. En este artículo se actualiza el conocimiento actual de la biología del SARS-CoV-2 y los posibles mecanismos de lesión miocárdica debido a toxicidades virales y respuestas inmunes del huésped.

Coronavirus disease 2019 (COVID-19) causes severe acute respiratory syndrome due to coronavirus 2 (SARS-CoV-2), and can be particularly detrimental to patients with underlying cardiovascular disease (CVD), and is a cause of morbidity and mortality. significant worldwide. The virus infects host cells through angiotensin-converting enzyme 2 (ACE2) receptors and their internalization of the complex into that cell. ACE2 is a key enzyme component of the renin-angiotensin-aldosterone (RAAS) system, degrading angiotensin (Ang) II, a peptide with multiple actions that promote CVD, and generating Ang- (1-7), which antagonizes the effects of Ang II . Furthermore, experimental evidence suggests that blocking SRAA by ACE inhibitors and Ang II type 1 receptor antagonists increases ACE2, which in part contributes to the benefit of these patients. This virus leads to lung disease, while causing acute myocardial injury and chronic damage to the cardiovascular system. This myocardial injury occurs in the most severe phase of COVID-19; but still, the pathophysiological mechanism of the injury was not clarified. Therefore, special attention should be paid to cardiovascular protection during treatment for COVID-19. Acute respiratory distress syndrome (ARDS) is a highmortality clinical disease, and ACE2 has a protective effect on this type of acute lung injury. Current research shows that the poor prognosis of COVID-19 patients is related to factors such as male gender, age> 60 years, underlying diseases: hypertension, diabetes and CVD, secondary ARDS, and other relevant factors. Although the data is limited, possible mechanisms of myocardial injury include direct viral entry through the ACE2 membrane receptor and host cell toxicity, hypoxia-related myocyte injury, and cytokine release syndrome. mediated by the immune system, further studies are needed to clarify the mechanism of cardiotoxicity and its prevention. This article updates current knowledge of the biology of SARS-CoV-2 and the possible mechanisms of myocardial injury due to viral toxicities and host immune responses.

A doença de coronavírus 2019 (COVID-19) causa síndrome respiratória aguda grave devido ao coronavírus 2 (SARSCoV-2) e pode ser particularmente prejudicial para pacientes com doença cardiovascular subjacente (DCV) e é uma causa de morbidade e mortalidade significativo em todo o mundo. O vírus infecta as células hospedeiras através dos receptores da enzima conversora de angiotensina 2 (ECA2) e sua internalização do complexo nessa célula. O ACE2 é um componente enzimático chave do sistema renina-angiotensina-aldosterona (SRAA), degradando a angiotensina (Ang) II, um peptídeo com múltiplas ações que promovem DCV e gerando Ang- (1-7), que antagoniza os efeitos da Ang II . Além disso, evidências experimentais sugerem que o bloqueio do SRAA por inibidores da ECA e antagonistas dos receptores Ang II tipo 1 aumenta a ECA2, o que em parte contribui para o benefício desses pacientes. Este vírus leva a doenças pulmonares, causando lesão miocárdica aguda e danos crônicos ao sistema cardiovascular. Essa lesão do miocárdio ocorre na fase mais grave do COVID-19; mas ainda assim, o mecanismo fisiopatológico da lesão não foi esclarecido. Portanto, atenção especial deve ser dada à proteção cardiovascular durante o tratamento para COVID-19. A síndrome do desconforto respiratório agudo (SDRA) é uma doença clínica de alta mortalidade e a ECA2 tem um efeito protetor sobre esse tipo de lesão pulmonar aguda. Pesquisas atuais mostram que o mau prognóstico dos pacientes com COVID-19 está relacionado a fatores como sexo masculino, idade> 60 anos, doenças subjacentes: hipertensão, diabetes e DCV, SDRA secundária e outros fatores relevantes. Embora os dados sejam limitados, os possíveis mecanismos de lesão do miocárdio incluem entrada viral direta através do receptor da membrana ACE2 e toxicidade das células hospedeiras, lesão de miócitos relacionados à hipóxia e síndrome de liberação de citocinas.mediados pelo sistema imunológico, são necessários mais estudos para esclarecer o mecanismo da cardiotoxicidade e sua prevenção. Este artigo atualiza o conhecimento atual da biologia da SARS-CoV-2 e os possíveis mecanismos de lesão do miocárdio devido a toxicidades virais e respostas imunes do hospedeiro.

Azilsartan causing metabolic encephalopathy

Angiotensin II receptor blockers (ARBs) are the antihypertensive drugs associated with side effects, majorly such ascough and electrolyte disturbance. Azilsartan is a newly marketed ARB in India, not even having a well-establishedadverse effect profile. Here, we present a 58-year-old female who was admitted to the emergency department showingsigns and symptoms of delirium, disorientation, and vomiting for 4 days. The patient is known to have coronaryartery disease so that she underwent coronary artery bypass grafting. She was recently started on azilsartan for herchronic hypertension, along with other drugs. The presence of electrolyte imbalance in laboratory reports and currentsymptoms suggested azilsartan-induced encephalopathy. The patient was recovered after discontinuation of azilsartan.This case enlightens the clinical characteristics, possible mechanism, and treatment strategy opted to correct thecondition.

Hyperkalemia in chronic kidney disease

SUMMARY Hyperkalemia is a frequent finding in patients with chronic kidney disease (CKD). This increase in serum potassium levels is associated with decreased renal ion excretion, as well as the use of medications to reduce the progression of CKD or to control associated diseases such as diabetes mellitus and heart failure. Hyperkalemia increases the risk of cardiac arrhythmia episodes and sudden death. Thus, the control of potassium elevation is essential for reducing the mortality rate in this population. Initially, the management of hyperkalemia includes orientation of low potassium diets and monitoring of patients' adherence to this procedure. It is also important to know the medications in use and the presence of comorbidities to guide dose reduction or even temporary withdrawal of any of the potassium retention-related drugs. And finally, the use of potassium binders is indicated in both acute episodes and chronic hyperkalemia.

RESUMO A hiperpotassemia é um achado frequente em pacientes com doença renal crônica (DRC). Esta elevação do nível sérico de potássio está associada à diminuição da excreção renal do íon, assim como ao uso de medicações para retardar a progressão da DRC ou para controlar doenças associadas, como diabetes mellitus e insuficiência cardíaca. A hiperpotassemia aumenta o risco de episódios de arritmia cardíaca e morte súbita. Assim, o controle da elevação de potássio é essencial para a diminuição da taxa de mortalidade nessa população. O manejo da hiperpotassemia inclui, inicialmente, orientação de dietas com baixo teor de potássio e acompanhamento da aderência dos pacientes a esse procedimento. Também é importante conhecer as medicações em uso e a presença de comorbidades, a fim de orientar a redução de doses ou até mesmo a suspensão temporária de alguma das drogas relacionadas à retenção de potássio. E, finalmente, o uso de quelantes de potássio é indicado tanto em episódios agudos como nos casos de hiperpotassemia crônica.

COVID-19 y el sistema renina, angiotensina, aldosterona. Una relación compleja / COVID-19 and the renin, angiotensin, aldosterone system. A complex relationship

Resumen La pandemia por COVID-19 ha tenido muy importantes repercusiones negativas, sanitarias, psicológicas, sociales y económicas para las personas, las familias, las comunidades, los países y para las para la humanidad en general. La interrelación con la edad y la presencia de enfermedades crónicas no trasmisibles (hipertensión, diabetes, obesidad, tabaquismo) parece ir mas lejos que lo que explicaría la prevalencia y distribución de ambas. Los medicamentos que actúan sobre el sistema renina-angiotensina-aldosterona, son pilares básicos en el manejo de estas enfermedades. Se sabe de tiempo atrás que estos fármacos aumentan en forma significativa la expresión en el tejido pulmonar de receptores para la enzima de conversión de angiotensina de tipo 2. Este hecho junto con el conocimiento de que la vía de entrada del virus a la célula es precisamente el receptor de ECA-2, inició una hipótesis, basada en evidencia de muy baja calidad, que rápidamente se generalizó en los medios de comunicación, de que el empleo de estos medicamentos podría ser negativo y que deberían suspenderse. La respuesta de prácticamente todas las sociedades científicas fue casi inmediata, con la indicación precisa de que no debería suspenderse el tratamiento con estos fármacos, puesto que la evidencia de su utilidad está basada en una evidencia muy sólida y de gran calidad. Casi simultáneamente también apareció la hipótesis, también basada en evidencia muy preliminar, de que estos medicamentos no solo resultan dañinos sino que son benéficos, tampoco se aceptan todavía como agentes para la prevención o tratamiento de esta enfermedad o sus complicaciones. La presente revisión relata los conocimientos actuales sobre la relación entre COVID-19 y SRAA.

Abstract The COVID-19 pandemic has had major negative health, psychological, social and economic repercussions for individuals, families, communities, countries and for humanity in general. The interrelation with age and the presence of chronic non-communicable diseases (hypertension, diabetes, obesity, smoking) seems to go further than what would be explained by the prevalence and distribution of both. The drugs that act on the renin-angiotensin-aldosterone system are in many cases the backbone for the management of these diseases, it has been known for a long time that these drugs significantly increase the expression of receptors for angiotensin conversion enzyme type 2 in the lung tissue. This fact, together with the knowledge that the route of entry of the virus into the cell is precisely the ACE-2 receptor, initiated a hypothesis, based on very low-quality evidence, which quickly became generalized in the media, that the use of these drugs could be negative and that they should be interrupted immediately. The response of practically all Scientific Societies was almost immediate, with the precise indication that treatment with these drugs should not be discontinued, since the evidence of their usefulness is based on very solid and high-quality evidence. Simultaneously, a different hypothesis also appeared, also based on very preliminary evidence, that these drugs are not only harmful but also beneficial, however these medicaments are not yet accepted as agents for the prevention or treatment of this disease or its complications. This review reports current knowledge on the relationship between COVID-19 and SRAA.

Changes of RAAS in atrial fibrillation model dogs after spinal cord stimulation and its inhibitory effect on atrial fibrillation / 吉林大学学报(医学版)

Objective: To investigate the changes of the serum indexes of renin-angiotensin-aldosterone system (RAAS) and atrial fibrillation burden in the atrial fibrillation model dogs underwent spinal cord stimulation (SCS) therapy, and to illuminate the therapeutic effect of SCS on the atrial fibrillation and its effect on RAAS Methods: A total of 24 healthy adult dogs were chosen The pacemakers and miniaturized insertable cardiac monitors were implanted into 16 dogs to establish the atrial fibrillation models by rapid right atrial pacing. Then 16 model dogs were divided into atrial fibrillation (AF) group and SCS group (n=8). The spinal cord stimulators were implanted into the dogs in SCS group to release stimulation for 12 weeks. And the rest dogs were regareded as blank control group (n=8). The atrial fibrillation burden of dogs in AF group and SCS group was monitored by miniaturized insertable cardiac monitors; the left and right atrial areas of dogs in three groups were measured by echocardiography; the serum levels of renin, angiotensin E (Ang E), aldosterone (ALD), angiotensin E type 1 receptor (AT1R), angiotensin E type 2 receptor (AT2R) and angiotensin converting enzyme 2 (ACE2) of the dogs in three groups were detected by ELISA method. Results: Compared with AF group, the atrial fibrillation burden of the dogs in SCS group was decresed obviously (P0. 05); the left and right atrial areas of the dogs in SCS group were larger than those in blank control group (P<0. 05). The serum ACE2 level of dogs in AF group was lower than that in blank control group (P<0. 05) and the levels of serum renin, Ang E, ALD, AT1R and AT2R of the dogs in AF group were all higher than those in blank control group (P<0. 05); the serum ACE2 level of the dogs in SCS group was higher than that in AF group (P<0. 05) and the levels of serum renin, Ang E, ALD, AT1R, and AT2R of the dogs in SCS group were all lower than those in AF group (P<0. 05). Compared with before modeling, the serum ACE2 level of dogs in AF group after modeling was decresed (P<0. 05), and the levels of serum renin, Ang E, ALD, AT1R, and AT2R were incresed (P<0. 05); compared with before treatment, the serum ACE2 level of the dogs in SCS group after treatment was incresed (P<0. 05), and the levels of serum renin, Ang E, ALD, AT1R, and AT2R were decresed (P<0.05). Conclusion: Atrial fibrillation can activate the RAAS. SCS therapy can suppress the atrial fibrillation and it can suppress RAAS activated by atrial fibrillation, so SCS can restraint the deterioration of atrial fibrillation. The serum RAAS indexes are so important observation indexes to evaluate the outcome of SCS in the treatment of atrial fibrillation.

Effect of Nature and Flavor Subdivision of Ephedrae Herba on Rats Model of Harmful Fluid Retention in Upper Jiao / 中国实验方剂学杂志

Objective: To study the effective substance foundation of Ephedrae Herba and explore its mechanism, in order to further enrich the theory of drug resistance of Ephedrae Herba.Method: In this experiment, a compound model was used to establish rat model of Harmful Fluid Retention in upper Jiao. The Rats were randomly divided into model group, captopril group (4.38 mg·kg-1), Ephedrae Herba decoction group(468 mg·kg-1), polysaccharide group (265.36 mg·kg-1), volatile oil group (2.34 mg·kg-1), alkaloid group(40.71 mg·kg-1) and phenolic acid group (210.60 mg·kg-1), and normal group (10 mL·kg-1). The normal group and the model group were given the same volume of normal saline for four weeks. The 24 h urine volume of rats was collected by metabolic cage method. The changes of heart and lung tissue morphology were observed under light microscope. The heart index, lung index, left ventricular ejection fraction(LVEF), left ventricular short axis shortening rate(LVFS) and pulmonary permeability index, number(LPI), lung dry-wet ratio(W/D), creatine kinase isoenzyme(CK-MB), angiotensin Ⅱ(Ang Ⅱ), aldosterone(ALD), cardiac aquaporin 1(AQP1), lung AQP1, aquaporin-3(AQP3) and kidney AQP1, aquaporin-2(AQP2), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) change were detected.Result: Compared with the normal group, heart and lungs of the model group were significantly damaged. The amount of 24 h urine, LVEF, LVFS of model rats were significantly reduced(Pα were significantly increased(PPα were significantly increased (PPα were significantly reduced (PPConclusion: Alkaloid components "Wen" and "Xin" are the effective substance basis of its action. The mechanism may be related to the inhibition of renin angiotensin aldosterone system (RAAS) and the anti-inflammatory effect.

RAAS antagonist therapy for prevention of atrial fibrillation in hypertension / 中华全科医师杂志

Hypertension is the most common and controlable risk factor of atrial fibrillation (AF).Resin-angiotensin-aldosterone system (RAAS) antagonist therapy may reduce atrial remodeling and hold promise as “upstream” therapy for AF,especially for the patients with left ventricular hypertrophy and left ventricular dysfunction.The RAAS antagonist therapy for prevention of AF in hypertensive patients needs to be further explored in large scale randomized studies.

Effects and mechanism of total phenols of Magnolia officinalis combined with Maijunan Tablets on blood pressure of spontaneous hypertensive rats / 中草药·英文版

Objective: Maijunan (MJA) Tablets is a protected variety of traditional Chinese medicine (TCM) consisted of Pueraria lobata, hydrochlorothiazide (HTCZ), Uncaria rhynchophylla (366:1:980) and excipient. In the present work, MJA was consisted of the total flavones of P. lobata, HCTZ and total alkaloids of U. rhynchophylla (40:11:75). The combination of MJA and the total phenols of Magnolia officinalis (M-MJA) was consisted of the total flavones of P. lobata, the total phenols of M. officinalis, HCTZ and the total alkaloids of U. rhynchophylla (40:40:11:75). The aim of this work was to examine the effect and mechanism of M-MJA on the blood pressure of spontaneous hypertensive rats (SHRs). Methods: Adult male SHRs were randomly divided into control group, MJA group (180 mg/kg·d), and the M-MJA group (218 mg/kg·d) (n = 5). SHRs were orally administered with M-MJA and MJA respectively once a day for 8 weeks, the blood pressure of SHRs was measured every two weeks, and the biochemical indicators related to blood pressures were detected at the last dosing. Results: After oral administration of M-MJA to SHRs once a day for 8 weeks, the systolic and diastolic blood pressures of SHRs were deceased significantly. M-MJA affected renin-angiotensin-aldosterone system by decreasing the levels of Ren, Ang II and ALD, affected the endothelial function by decreasing the levels of ET-1 and 20-HETE, and increasing the level of eNOS, affected the oxidative stress by increasing the protein expression of Nrf2 and the activities of HO-1 and GSH-Px, and decreasing the protein expression of CYP2E1 and CYP4A, as well as the content of MDA. Conclusion: These results indicated that M-MJA could regulate the renin-angiotensin-aldosterone system, improve endothelial function, and inhibit CYP4A activity to reduce the production of 20-HETE, alleviate the oxidative stress disorder of the visceral organs, and eventually exert antihypertensive effect. Additionally, the anti-oxidant ability, regulating the renin-angiotensin-aldosterone system and improving endothelial function of M-MJA are more powerful than that of MJA, suggesting that M-MJA may have a better anti-hypertensive effect than MJA.

Balancing Effect of Biejiajian Oral Liquid () on ACE-Ang II-AT1R Axis and ACE2-Ang-(1-7)-Mas Axis in Rats with CCl-Induced Hepatic Fibrosis / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the effect of Biejiajian Oral Liquid (, BOL) on CCl-induced hepatic fibrosis in rats by detecting the changes in the levels of angiotensin II (Ang II), angiotensin-(1-7) [Ang-(1-7)], angiotensin-converting enzyme (ACE), ACE2, angiotensin II type 1 receptor (AT1R), Mas, etc. METHODS: A total of 180 Wistar rats were randomly divided into two groups by random digital table method: prevention experiment and treatment experiment. Each group was further subdivided into the following 6 subgroups: normal control group, model group, vitamin E [100 mg/(kg·d), VE] group, enalapril [10 mg/(kg·g), Ena] group, high-dosage [20 g/(kg·d)] BOL group, and low-dosage [10 g/(kg·d)] BOL group. The hepatic fibrosis rat model was established by subcutaneous injection of CCl for 6 weeks. Prevention experiment and treatment experiment were administered with specific drugs at different times. At the end of treatment experiment, the pathological changes of liver were observed after hematoxylin-eosin staining. The expressions of ingredients in renin-angiotensin-aldosterone system (RAAS) such as AngII, Ang-(1-7), ACE, ACE2, AT1R, Mas, renin, CYP11B2 and angen in liver were detected by enzyme linked immunosorbent assay, immunohistochemistry method or reverse transcription-polymerase chain reaction, respectively.</p><p><b>RESULTS</b>The levels of AngII and Ang-(1-7) at the 6th week increased by 496.10% and 73.64%, respectively, compared with those at the 2nd week in the model group (P<0.01). With prevention or treatment with high-dosage BOL, there was an evident reduction of AngII level but an improvement of Ang-(1-7) level. Specifically, AngII level of high-dosage group decreased by 77.50% in prevention experiment (P=0.000) and by 76.93% in treatment experiment (P=0.002) compared with that in the model group. Ang-(1-7) level increased by 91.69% in prevention experiment (P=0.006) and by 70.77% in the treatment experiment (P=0.010) compared with that in the model group. The expression levels of mRNA of renin, ACE, CYP11B2, angen and AT1R decreased by 58.15%, 99.90%, 99.84%, 99.99% and 99.99% (all P<0.01), respectively.</p><p><b>CONCLUSIONS</b>BOL could help resist liver fibrosis in rats by enhancing the level of each ingredient in ACE2-Ang-(1-7)-Mas axis, while decreasing the level of each ingredient in ACE-AngII-AT1R axis. To some extent, BOL could enhance the regulation of RAAS in rats with CCl-induced hepatic fibrosis.</p>

Effects of sodium hydrosulfide on cardiac function and activity of renin-angiotensin-aldosterone system in rats with chronic heart failure / 中国病理生理杂志

AIM:To investigate the effect of sodium hydrosulfide(NaHS)on cardiac function and activity of renin-angiotensin(Ang)-aldosterone(ALD)system(RAAS)in the rats with chronic heart failure(CHF).METHODS:The CHF rat model was established by abdominal aortic coarctation.SD rats were randomly divided into sham operation group,model group,low dose of NaHS group and high dose of NaHS group(n=6).The left ventricular end-diastolic di-ameter(LVEDD), left ventricular end-systolic diameter(LVESD)and left ventricular ejection fraction(LVEF)were measured before and after treatment by echocardiography in each group.The levels of renin,AngⅡand ALD in the plasma were measured by ELISA.The expression of angiotensin-converting enzyme(ACE)and angiotensin Ⅱ type 1 receptor (AT1R)at mRNA and protein levels in the myocardium tissues was determined by qPCR and Western blot,respectively. RESULTS:After treatment with NaHS,compared with model group and before treatment,LVEDD and LVESD in low dose of NaHS group and high dose of NaHS group were decreased significantly, while LVEF was increased significantly(P<0.05).Compared with low dose of NaHS group,LVEDD and LVESD were decreased,while LVEF was increased in high dose of NaHS group(P<0.05).Compared with sham operation group,the levels of renin,AngⅡand ALD in the plasma of model group were significantly increased(P<0.05),and the expression of ACE and AT1R at mRNA and protein levels in the myocardium tissues of model group were significantly increased(P<0.05).Compared with model group,the plas-ma levels of renin,AngⅡand ALD in low dose of NaHS group and high dose of NaHS group were significantly decreased (P<0.05),and the myocardial expression of ACE and AT 1R at mRNA and protein levels was significantly down-regulated (P<0.05).The plasma levels of renin,AngⅡand ALD,and the myocardial expression of ACE and AT 1R at mRNA and protein levels in high dose of NaHS group were significantly lower than those in low dose of NaHS group(P<0.05). CONCLUSION:NaHS inhibits the activation of RAAS,thus improving the cardiac function of CHF rats,and the effect of high-dose NaHS is better than that of low-dose NaHS.