Importance of survey demographic questions to foster inclusion in medicine and research and reduce health inequities for LGBTQIA2S+ individuals.

A clear, inclusive, and accurate approach to the collection of demographic information in clinical research and medical practice is critical to understanding the healthcare needs of the specific population. Inclusive demography constitutes appropriate and accurate characterization of an individual's sexual orientation and gender identity (SOGI) data. Appropriate demography fosters sense of inclusion and belonging for those belonging to medically marginalized communities such as the lesbian, gay, bisexual, transgender, queer, intersex, asexual, and Indigenous Two-Spirit (LGBTQIA2S+) communities and improves health outcomes. Acquiring inclusive demographics in healthcare research is needed for the following critical reasons. First, LGBTQIA2S+ individuals experience undue psychological harm when their identities are not appropriately captured in survey data, promoting further alienation of the LGBTQIA2S+ community in medicine and research. Second, LGBTQIA2S+ populations are disproportionately burdened by several major cardiovascular and cardiovascular-associated diseases, including hypertension and diabetes. Failure to include these populations, and accurately characterize their participation, in research leads to failure to identify associations between identities and disease, resulting in worse health outcomes. Furthermore, this lack of precision in current data for sex, gender, and sexual orientation may lead to inaccurate data for all populations, not just the LGBTQIA2S+ community. Finally, there are currently major political and social threats and attacks on the LGBTQIA2S+ community and, in particular, on transgender and gender-diverse individuals. Proper medical inclusion and advocacy for the LGBTQIA2S+ community by the medical community may help protect the community from further undue harm through creating sense of belonging and reductions in marginalization-related health inequities.

Attachment, Jealousy, and Conjugal Violence / Apego, Ciúme e Violência Conjugal

Abstract Psychological aggression is the most common manifestation of intimate partner violence. Literature demonstrates that attachment and jealousy can predict intimate partner violence. The aim of this study was to test a theoretical model in which jealousy is a mediator between attachment and psychological aggression. This is a quantitative study, with cross-sectional and explanatory design. A sample of 600 people, aged between 18 and 65 years old, residing in 13 Brazilian states, was investigated. A Sociodemographic data questionnaire, Psychological Aggression Sub-scales (CTS2), Questionnaire on the Affective Relationships (QAR), Interpersonal Jealousy Scale (IJC) and Adult Attachment Scale (AAS 2) were used. Structural equation modeling indicated that jealousy functioned as a mediator between attachment and psychological aggressions, alerting to the possibility of prevention in conjugality through early interventions.

Resumo A agressão psicológica é a manifestação mais comum da violência conjugal. A literatura demonstra que o apego e o ciúme podem predizer a violência conjugal. O objetivo deste estudo foi testar um modelo teórico em que o ciúme é um mediador entre o apego e a agressão psicológica. Trata-se de um estudo quantitativo, com delineamento transversal e explicativo. Foi investigada uma amostra de 600 pessoas, com idades entre 18 e 65 anos, residentes em 13 estados brasileiros. Foi utilizado um questionário de dados sociodemográficos, uma subescala de agressão psicológica (CTS2), questionário de relacionamentos afetivos (QAR), Escala interpessoal de ciúme (IJC) e Escala de apego adulto (AAS 2). Por meio de modelagem de equações estruturais, os resultados indicaram que o ciúme funcionou como mediador entre o apego e a agressão psicológica, alertando para a possibilidade de intervenções precoces na conjugalidade.

Seria o ciúme mediador entre as experiências na família de origem e a violência física na conjugalidade? / Is jealousy a mediator between experiences in the family of origin and physical violence in conjugality? / Serián los celos mediadores entre las vivencias en la familia de origen y la violencia física en la conjugalidad?

A violência conjugal é um fenômeno multideterminado, o qual sofre impacto de experiências precoces e atuais. O objetivo deste estudo foi testar um modelo teórico no qual o ciúme é mediador entre as experiências na família de origem e a violência física conjugal. Trata-se de um estudo com delineamento quantitativo, transversal e explicativo. Contou com uma amostra de 600 pessoas, de 18 a 65 anos, residentes em 13 estados brasileiros. Os instrumentos foram questionário sociodemográfico, FBQ, CTS2 e ICR, em uma coleta por formulário eletrônico na internet. Modelagem de equações estruturais foi utilizada para testar a validade empírica do modelo teórico. Os resultados indicaram que o ciúme media parcialmente as experiências na família de origem e a ocorrência da violência conjugal. Os dados apontam para a necessidade de atenção ao ciúme nos relacionamentos amorosos, como forma de atuar na prevenção às situações de violência conjugal. (AU)

Conjugal violence is a multidetermined phenomenon, which is impacted by early and present experiences. The objective of this study was to test a theoretical model in which jealousy mediates between experiences in the family of origin and physical domestic violence. This was a quantitative, transversal, and explanatory study, which counted on a sample of 600 people, aged from 18 to 65 years, from 13 Brazilian states. The instruments included a sociodemographic questionnaire, the FBQ, the CTS2, and the RJI, all collected electronically. Structural equation modeling was used to test the empirical validity of the theoretical model. The results indicated that jealousy partially mediates the experiences in the family of origin and the occurrence of conjugal violence. The data point to the need for attention to jealousy in love relationships, as a way of acting in the prevention of situations of conjugal violence. (AU)

La violencia conyugal es un fenómeno multideterminado, el cual sufre impacto de experiencias tempranas y actuales. El objetivo de este estudio fue testar un modelo teórico en el cual los celos son mediadores entre las vivencias en la familia de origen y la violencia física conyugal. Se trata de un estudio con delineamiento cuantitativo, transversal y explicativo. Se contó con una muestra de 600 personas, de 18 a 65 años, residentes en 13 estados brasileños. Los instrumentos fueron el cuestionario sociodemográfico, FBQ, CTS2 e ICR, recogidos por medio de formulario electrónico en internet. El modelo de ecuaciones estructurales fue utilizado para testar la validez empírica del modelo teórico. Los resultados indicaron que los celos midieron parcialmente las vivencias en la familia de origen y la ocurrencia de la violencia conyugal. Los datos señalan la necesidad de atención de los celos en las relaciones amorosas, como forma de actuar en la prevención de las situaciones de violencia conyugal. (AU)

Quality of life of elders in the primary health care in Uberaba, MG / Qualidade de vida de idosos da atenção primária à saúde em Uberaba, MG

This study aimed to evaluate social and economic predictors, as well social behavior and its influence on the quality of life of elders who use the primary health care network of Uberaba, Minas Gerais. Methods: Descriptive, exploratory, cross-sectional and quantitative study, conducted with 248 60 year old or older subjects, from November 2016 to May 2017. A structured questionnaire was applied to evaluate sociodemographic data, health conditions and life habits as well the WHOQOL-Bref and the WHOQOL-Old. The analysis were conducted through relative frequencies and t-test as well multiple linear regression were used to associate variables. The study was approved by the Committee of Ethics in Researches with Human Beings of the Federal University of the Triângulo Mineiro (CEP/UFTM). Results: Most elders were women, catholic, with 4 years or more of formal education, had partners, a sexually inactive life, and were retired. The linear regression analysis, found a positive and light or moderate association between sexual life and the physical, social, and environmental domains, and the past, present and future activities facet. The educational level variable had a positive and light association with the psychological domain, whereas the variable occupation had a negative and light association with the death and dying facet. Conclusions: The results found show an important social impact regarding the studied population, making it clear that public policies should be created and executed as to offer subsidies for actions which are specifically targeted at the QoL of elders.

Este estudo teve como objetivo avaliar os preditores sociais e econômicos, bem como o comportamento social e sua influência na qualidade de vida dos idosos que utilizam a rede de Atenção Primária à Saúde de Uberaba, Minas Gerais. Métodos: Estudo descritivo, exploratório, transversal e quantitativo, realizado com 248 pessoas de 60 anos ou mais, entre novembro de 2016 a maio de 2017. Foi aplicado um questionário estruturado para avaliar os dados sociodemográficos, condições de saúde e hábitos de vida, bem como o WHOQOL-Bref e o WHOQOL-Old. A análise foi realizada através de freqüências relativas e teste t, bem como regressão linear múltipla foram utilizadas para associar variáveis. O estudo foi aprovado pelo Comitê de Ética em Pesquisa com Seres Humanos da Universidade Federal do Triângulo Mineiro (CEP / UFTM). Resultados: A maioria dos idosos eram mulheres, católicas, com 4 anos ou mais de educação formal, tinham parceiros, uma vida sexualmente inativa e eram aposentadas. A análise de regressão linear, encontrou uma associação positiva leve ou moderada entre a vida sexual e os domínios físico, social e ambiental, e facetas de atividades passadas, presentes e futuras. A variável nível educacional teve uma associação positiva e leve com o domínio psicológico, enquanto que a variável ocupação teve uma associação negativa e leve com a faceta de morte e morrer. Conclusões: Os resultados encontrados mostram um impacto social importante em relação à população estudada, deixando claro que as políticas públicas devem ser criadas e executadas de forma a oferecer subsídios para ações especificamente voltadas para a QV dos idosos.

Infidelidade na perspectiva de homens e mulheres / Infidelity from the perspective of men and women

O presente estudo investigou as concepções de infidelidade de homens e mulheres que estão em um relacionamento monogâmico e as possíveis motivações para o comportamento afetivo-sexual extra diádico. Trata-se de uma pesquisa quantitativa e descritiva com 275 participantes, 211 mulheres e 65 homens, com idades entre 18 e 65 anos, residentes de 16 estados brasileiros. A coleta ocorreu via internet por meio do preenchimento de dois questionários. As concepções de infidelidade referiram-se à quebra de contrato/confiança e envolvimento afetivo/sexual. Foram comportamentos considerados infidelidade ter relações sexuais, beijar, flertar e envolver-se virtualmente. A motivação envolveu insatisfação conjugal/sexual, insegurança, medo, carência, entre outros motivos. Os resultados corroboram a literatura e sugerem a necessidade de atentar para transições e dinamismo nas relações afetivo-sexuais.

The aim of this study was to investigate conceptions of infidelity for individuals who are in a monogamous relationship and the motivations for extra-dyadic affective-sexual behavior. This is a descriptive quantitative research with 275 people, 211 women and 65 men, aged 18-65 years, from 16 Brazilian states participated. The collected by internet through two questionnaires. The conception of infidelity involves break of contract/trust and affective and sexual involvement. The behaviors considered infidelity were having sex, kissing, flirting or virtual relating. The motivation involved marital/sexual dissatisfaction, insecurity, fear, lack, among other reasons. The results corroborate the literature and suggest the need to attention to the process of transition and dynamism in affective-sexual relationships.

Pais encarcerados: a percepção de mães e crianças sobre a relação pais-filhos / Incarcerated parents: the perception of mothers and children on the parent-child relationship

Objetivou-se compreender como crianças e suas mães avaliam o aprisionamento paterno e suas repercussões na dinâmica familiar e no desenvolvimento infantil. Participaram três crianças, com faixa etária entre sete e nove anos, sendo duas delas irmãs e as duas mães. Utilizou-se como instrumento uma entrevista semiestruturada e a hora do jogo diagnóstica. A análise foi baseada em estudo de casos múltiplos. Os resultados indicaram que o aprisionamento da figura paterna produz grande impacto na relação entre pais e filhos, seja pelo distanciamento físico, pela carência emocional e até mesmo por questões financeiras. Além disso, o tratamento destinado às mães e às crianças nos presídios, assim como os procedimentos de revista a que são submetidas, merecem atenção dos profissionais da saúde.(AU)

This study aimed to understand how children and their mothers assess parental imprisonment and its effects on family dynamics and child development. Participated three children, with ages between seven and nine, being two of them sisters and two mothers. The instruments used were a semi-structured interview and the game time diagnosis. The analysis was based on multiple cases study. The results indicated that the imprisonment of the father figure produces great impact on the relationship between parents and children, either by physical distance, the emotional deprivation and even for financial reasons. In addition, treatment for mothers and children in prisons, as well as inspection procedures to which they are subject, deserve the attention of health professionals.(AU)

Predictors of marital physical violence: personal and relational characteristics / Preditores da violência física conjugal: características pessoais e relacionais / Predictores de violencia física conyugal: características personales y relacionales

Conjugal violence is a complex phenomenon that deserves attention because of its prevalence. The aim of this study was to verify the predictive power of the family-of-origin experiences, early maladaptive schemas, love, marital adjustment and family climate to marital physical violence occurrence. In this quantitative, correlational and explanatory study 186 men and 186 women took part, aged from 19 to 81 (M=41,17; SD=12,75). The instruments used measured general information, family of origin (FBQ), maladaptive schemes (YSQs), love (TLS), marital adjustment (DAS), family climate (FCI) and marital conflicts (CTS2). The results showed an association between the studied variables. In addition, the variables family conflict and sexual abuse in childhood were predictive of physical violence committed by women, while marital dissatisfaction was the predictor of marital violence committed by men. In view of the results, it can be established that the phenomenon of violence in intimate relationships is multidetermined, requiring attention from health professionals. (AU)

A violência conjugal é um fenômeno complexo que merece atenção pela alta prevalência. O objetivo deste estudo foi verificar o poder preditivo de experiências na família de origem, esquemas iniciais desadaptativos, amor, ajustamento conjugal e clima familiar para a ocorrência de violência física conjugal. Participaram deste estudo, quantitativo, correlacional e explicativo, 186 homens e 186 mulheres, com idades entre 19 a 81 anos (M=41,17; DP=12,75). Os instrumentos utilizados mediram informações gerais, família de origem (FBQ), esquemas desadaptativos (IEDs), amor (ETAS), ajustamento conjugal (DAS), clima familiar (ICF) e conflitos conjugais (CTS2). Os resultados evidenciaram associação entre as variáveis estudadas. Além disso, as variáveis conflito familiar e abuso sexual na infância foram preditoras da violência física cometida pelas mulheres, enquanto que a insatisfação conjugal foi a variável preditora da violência conjugal cometida pelos homens. A partir dos resultados foi possível constatar quanto o fenômeno da violência em relacionamentos íntimos é multideterminado, exigindo atenção dos profisisonais da saúde. (AU)

La violencia conjugal es un fenómeno complejo que merece atención por su alta prevalencia. El objetivo de este estudio fue verificar el poder predictivo de experiencias en la familia de origen, esquemas iniciales desadaptativos, amor, ajuste conjugal y el clima familiar para la aparición de violencia física conjugal. Participaron deste estudio cuantitativo, correlacional y explicativo 186 hombres y 186 mujeres, con edades entre 19 y 81 años (M = 41,17, SD = 12,75). Los instrumentos utilizados midieron informaciones generales, familia de origen (FBQ), esquemas desadaptativos (IEDs), amor (ETAS), ajuste conyugal (DAS), clima familiar (ICF) y conflictos conyugales (CTS2). Los resultados mostraron asociación entre las variables estudiadas. Además, las variables conflicto familiar y abuso sexual en la infancia fueron predictores de la violencia física cometida por las mujeres, mientras que la insatisfacción conyugal fue la variable predictora de la violencia conjugal cometida por los hombres. Los resultados muestran que el fenómeno de violencia en relacionamientos íntimos es multi-determinado, requiriendo atención de profesionales de la salud. (AU)

Rel@cionamentos.com: Diferenciando os Relacionamentos Amorosos Mediados e não Mediados pela Internet / Rel@tions.com: Differentiating Internet Mediated and Non-Mediated Love Relationships / Rel@ciones.com: Diferenciando las Relaciones Amorosas Mediadas y no Mediadas por Internet

Resumo O objetivo deste estudo quantitativo foi descrever o perfil discriminante entre relacionamentos amorosos mediados pela internet e relacionamentos amorosos não mediados por esta de 86 participantes. As variáveis que discriminaram os grupos foram decisão/compromisso, paixão, intimidade, satisfação, tempo geral de uso diário de internet, tempo diário de uso de internet direcionado para manter contato social e problemas conjugais. A internet tem sido utilizada para contatos amorosos, porém os resultados deste estudo indicam que ela serve essencialmente como meio para aproximar pessoas que talvez nunca se encontrassem sem esse recurso; contudo, sugere-se que a continuidade do relacionamento depende do encontro presencial.

Abstract The aim of this study quantitative is to describe the discriminant profile between loving relationships mediated and unmediated by the Internet 86 participants. The variables that distinguished the groups were decision/commitment, passion, intimacy, satisfaction, overall time of daily Internet use, daily Internet time directed to maintain social contact and relationship problems. The Internet has been used for the development of relationships, however, the results suggest that it serves primarily as a way of bringing people who may never meet without the help of this technological tool together. Although the continuity of the relationship with higher levels of satisfaction depends on the personal meeting.

Resumen El objetivo de este estudio cuantitativo fue describir el perfil discriminante entre relaciones amorosas mediadas por internet y relaciones amorosas no mediadas por esta de 86 participantes. Las variables que discriminaron los grupos fueron decisión/compromiso, pasión, intimidad, satisfacción, tiempo general de uso diario de internet, tiempo diario de uso de internet para mantener contacto social y problemas conyugales. El internet se ha utilizado para contactos amorosos, pero los resultados del estudio señalan que ella sirve esencialmente como medio para acercar personas que tal vez nunca se hubieran encontrado sin este recurso; sin embargo, se sugiere que la continuidad de la relación depende del encuentro presencial.

Central Angiotensin-II Increases Blood Pressure and Sympathetic Outflow via Rho Kinase Activation in Conscious Rabbits.

Elevated sympathetic tone and activation of the renin-angiotensin system are pathophysiologic hallmarks of hypertension, and the interactions between these systems are particularly deleterious. The importance of Rho kinase as a mediator of the effects of angiotensin-II (AngII) in the periphery is clear, but the role of Rho kinase in sympathoexcitation caused by central AngII is not well established. We hypothesized that AngII mediates its effects in the brain by the activation of the RhoA/Rho kinase pathway. Chronically instrumented, conscious rabbits received the following intracerebroventricular infusion treatments for 2 weeks via osmotic minipump: AngII, Rho kinase inhibitor Fasudil, AngII plus Fasudil, or a vehicle control. AngII increased mean arterial pressure over the course of the infusion, and this effect was prevented by the coadministration of Fasudil. AngII increased cardiac and vascular sympathetic outflow as quantified by the heart rate response to metoprolol and the depressor effect of hexamethonium; coadministration of Fasudil abolished both of these effects. AngII increased baseline renal sympathetic nerve activity in conscious animals and impaired baroreflex control of sympathetic nerve activity; again Fasudil coinfusion prevented these effects. Each of these end points showed a statistically significant interaction between AngII and Fasudil. Quantitative immunofluorescence of brain slices confirmed that Rho kinase activity was increased by AngII and decreased by Fasudil. Taken together, these data indicate that hypertension, elevated sympathetic outflow, and baroreflex dysfunction caused by central AngII are mediated by Rho kinase activation and suggest that Rho kinase inhibition may be an important therapeutic target in sympathoexcitatory cardiovascular diseases.

Acolhimento institucional: considerações sobre a forma como o cuidado subjetivo se apresenta no cotidiano de trabalho dos educadores sociais / Residential care: considerations on how subjective care is presented in the daily work of social educators

Cuidado Subjetivo refere-se a todo cuidado dispensado em função de um indivíduo em sua singularidade e que vai além do investimento voltado ao seu bem-estar físico. Buscou-se investigar, através da percepção de três educadores sociais de instituições de acolhimento, a forma como o cuidado subjetivo se apresenta em seu cotidiano de trabalho. Neste estudo qualitativo, descrito e exploratório, discute-se sobre quais as demandas reais do acolhimento institucional na atualidade e identificam-se quais os pontos que aparecem como constituintes, especialmente no que se refere às noções de cuidado que permeiam o trabalho nestes locais. Os resultados revelam uma ideia de cuidado bastante atrelada à aprendizagem e superficial no que se refere ao cuidado específico com o indivíduo, o que parece surgir como reflexo dos valores contemporâneos, das construções sociais e de seu consequente impacto no regulamento das instituições.

Subjective care refers to all care dispensed to an individual in its uniqueness and that goes beyond his physical well-being investment. We sought to investigate, through the perception of three social educators from host institutions, how the subjective care is present in their daily work. In this qualitative, descriptive and exploratory study, we discuss about what are the real demands of residential care today and identifies the points that appear as constituents, especially with regard to the care notions that pervade the work in these places. The results reveal a perception of care quite linked to learning and superficial in relation to the specific care of the individual, which seems to emerge as a reflection of contemporary values, social construction and its consequent impact on the regulation of institutions.

Central mechanisms for exercise training-induced reduction in sympatho-excitation in chronic heart failure.

The control of sympathetic outflow in the chronic heart failure (CHF) state is markedly abnormal. Patients with heart failure present with increased plasma norepinephrine and increased sympathetic nerve activity. The mechanism for this sympatho-excitation is multiple and varied. Both depression in negative feedback sensory control mechanisms and augmentation of excitatory reflexes contribute to this sympatho-excitation. These include the arterial baroreflex, cardiac reflexes, arterial chemoreflexes and cardiac sympathetic afferent reflexes. In addition, abnormalities in central signaling in autonomic pathways have been implicated in the sympatho-excitatory process in CHF. These mechanisms include increases in central Angiotensin II and the Type 1 receptor, increased in reactive oxygen stress, upregulation in glutamate signaling and NR1 (N-methyl-D-aspartate subtype 1) receptors and others. Exercise training in the CHF state has been shown to reduce sympathetic outflow and result in increased survival and reduced cardiac events. Exercise training has been shown to reduce central Angiotensin II signaling including the Type 1 receptor and reduce oxidative stress by lowering the expression of many of the subunits of NADPH oxidase. In addition, there are profound effects on the central generation of nitric oxide and nitric oxide synthase in sympatho-regulatory areas of the brain. Recent studies have pointed to the balance between Angiotensin Converting Enzyme (ACE) and ACE2, translating into Angiotensin II and Angiotensin 1-7 as important regulators of sympathetic outflow. These enzymes appear to be normalized following exercise training in CHF. Understanding the precise molecular mechanisms by which exercise training is sympatho-inhibitory will uncover new targets for therapy.

Love and marital quality in romantic relationships mediated and non-mediated by internet / O amor e a qualidade conjugal em relacionamentos amorosos mediados e não mediados pela internet / Amor y la Calidad del Matrimonio en las Relaciones Amorosas Mediadas y No Mediadas por Internet

Love is one of the most desired feelings by human beings. According to the triangular theory of love, it is composed of three elements: intimacy, passion and decision/commitment, which constitutes a dimension related to the quality of love the partners perceive in their relationship. This study aims to compare the three elements of love and marital quality of 86 Internet users (43 in a relationship mediated by the Internet and 43 with a physical relationship). The results indicate that there is a significant difference in the intimacy, the decision/commitment and the whole dimension of love, as well as in the marital quality between partners who have a relationship mediated by Internet and the ones in a physical relationship. We can conclude that the Internet is a great tool for people to meet, but that it is important for the relationship to develop in a face-to-face context.

O amor é um dos sentimentos mais desejados pelo ser humano. De acordo com a teoria triangular do amor, este é composto por três elementos: intimidade, paixão e decisão/compromisso, constituindo-se em uma dimensão relacionada à qualidade percebida pelos cônjuges no seu relacionamento. O objetivo deste estudo quantitativo foi comparar os três elementos do amor e a qualidade conjugal de 86 usuários de Internet divididos em dois grupos (43 em um relacionamento amoroso mediado pela Internet e 43 em um relacionamento presencial). Os resultados revelaram diferença significativa na intimidade, na decisão/compromisso e na dimensão total do amor, bem como na qualidade conjugal, entre os usuários que possuem um relacionamento mediado pela Internet e os usuários em relacionamentos presenciais. Conclui-se que a Internet é uma excelente ferramenta para que pessoas se conheçam, porém é importante que o relacionamento se desenvolva em um contexto presencial.

El amor es uno de los sentimientos más deseados por los seres humanos. La teoría triangular del amor cree que está compuesto por tres componentes: intimidad, pasión y decisión/compromiso, dimensiones relacionadas con la percepción de los cónyuges a cerca de la calidad de su relacionamiento. La finalidad de este estudio cuantitativo fue comparar los tres elementos del amor y de la calidad marital en 86 usuarios de Internet divididos en dos grupos (43 en una relación de amor mediada por la Internet y 43 en un relacionamiento presencial). Los datos mostraron diferencias significativas en la intimidad, en la dimensión decisión/compromiso y en la dimensión total del amor, así como en la calidad del matrimonio entre los usuarios que tienen una relación mediada por la Internet y los usuarios en las relaciones presenciales. Llegamos a la conclusión de que Internet es una excelente herramienta para que las personas se encuentran, pero es importante que la relación se desarrolle en un contexto presencial.

Simvastatin treatment attenuates increased respiratory variability and apnea/hypopnea index in rats with chronic heart failure.

Cheyne-Stokes respiration and cardiac arrhythmias are associated with increased morbidity and mortality in patients with chronic heart failure (CHF). Enhanced carotid body chemoreflex (CBC) sensitivity is associated with these abnormalities in CHF. Reduced carotid body (CB) nitric oxide and nitric oxide synthase (NOS) levels play an important role in the enhanced CBC. In other disease models, Simvastatin (statin) treatment increases endothelial NOS, in part, by increasing Krüppel-like Factor 2 expression. We hypothesized that statin treatment would ameliorate enhanced CBC sensitivity as well as increased respiratory variability, apnea/hypopnea index, and arrhythmia index, in a rodent model of CHF. Resting breathing pattern, cardiac rhythm, and the ventilatory and CB chemoreceptor afferent responses to hypoxia were assessed in rats with CHF induced by coronary ligation. CHF was associated with enhanced ventilatory and CB afferent responses to hypoxia as well as increased respiratory variability, apnea/hypopnea index, and arrhythmia index. Statin treatment prevented the increases in CBC sensitivity and the concomitant increases in respiratory variability, apnea/hypopnea index, and arrhythmia index. Krüppel-like Factor 2 and endothelial NOS protein were decreased in the CB and nucleus tractus solitarii of CHF animals, and statin treatment increased the expression of these proteins. Our findings demonstrate that the increased CBC sensitivity, respiratory instability, and cardiac arrhythmias observed in CHF are ameliorated by statin treatment and suggest that statins may be an effective treatment for Cheyne-Stokes respiration and arrhythmias in patient populations with high chemoreflex sensitivity.

The central renin-angiotensin system and sympathetic nerve activity in chronic heart failure.

CHF (chronic heart failure) is a multifactorial disease process that is characterized by overactivation of the RAAS (renin-angiotensin-aldosterone system) and the sympathetic nervous system. Both of these systems are chronically activated in CHF. The RAAS consists of an excitatory arm involving AngII (angiotensin II), ACE (angiotensin-converting enzyme) and the AT1R (AngII type 1 receptor). The RAAS also consists of a protective arm consisting of Ang-(1-7) [angiotensin-(1-7)], the AT2R (AngII type 2 receptor), ACE2 and the Mas receptor. Sympatho-excitation in CHF is driven, in large part, by an imbalance of these two arms, with an increase in the AngII/AT1R/ACE arm and a decrease in the AT2R/ACE2 arm. This imbalance is manifested in cardiovascular-control regions of the brain such as the rostral ventrolateral medulla and paraventricular nucleus in the hypothalamus. The present review focuses on the current literature that describes the components of these two arms of the RAAS and their imbalance in the CHF state. Moreover, the present review provides additional evidence for the relevance of ACE2 and Ang-(1-7) as key players in the regulation of central sympathetic outflow in CHF. Finally, we also examine the effects of exercise training as a therapeutic strategy and the molecular mechanisms at play in CHF, in part, because of the ability of exercise training to restore the balance of the RAAS axis and sympathetic outflow.

NF-κB and CREB are required for angiotensin II type 1 receptor upregulation in neurons.

Nuclear factor kappa B (NF-κB) and the Ets like gene-1 (Elk-1) are two transcription factors that have been previously established to contribute to the Angiotensin II mediated upregulation of Angiotensin II type 1 receptor (AT1R) in neurons. The cAMP response element binding protein (CREB) is another transcription factor that has also been implicated in AT1R gene transcription. The goal of the current study was to determine if NF-κB and CREB association was required for AT1R upregulation. We hypothesized that the transcription of the AT1R gene occurs via an orchestration of transcription factor interactions including NF-κB, CREB, and Elk-1. The synergistic role of CREB and NFκB in promoting AT1R gene expression was determined using siRNA-mediated silencing of CREB. Electrophorectic Mobility Shift Assay studies employing CREB and NF-κB demonstrated increased protein - DNA binding as a result of Ang II stimulation which was blunted by siRNA silencing of CREB. Upstream inhibition of p38 mitogen activated protein kinase (p38 MAPK) with SB203580 or inhibition of the calmodulin kinase (CAMK) pathway using KN-62 blunted changes in CREB and NF-κB expression. These findings suggest that Ang II may activate multiple signaling pathways involving p38 MAPK leading to the activation of NF-κB and CREB, which feed back to upregulate the AT1R gene. This study provides insight into the molecular mechanisms involving multiple transcription factor activation in a coordinated fashion which may be partially responsible for sympathoexcitation in clinical conditions associated with increased activation of the renin angiotensin system.

Unilateral renal denervation improves autonomic balance in conscious rabbits with chronic heart failure.

A hallmark of chronic heart failure (CHF) is an increased sympathetic tone resulting in autonomic imbalance. Renal denervation (DNx) in CHF patients has resulted in symptomatic improvement, but the protective mechanisms remain unclear. We hypothesized in CHF, unilateral renal DNx would improve cardiac autonomic balance. The present study used conscious, chronically instrumented New Zealand White rabbits undergoing renal DNx prior to pacing-induced CHF. Four treatment groups were used: nonpace, non-DNx [Sham-Innervated (Sham-INV)], nonpace DNx (sham-DNx), pace non-DNx (CHF-INV) or pace DNx (CHF-DNx). We examined several markers indicative of autonomic balance. Baroreflex sensitivity and time domain heart rate variability (HRV) were both decreased in the CHF-INV group compared with sham-INV and were restored to sham levels by renal DNx. Power spectral analysis indicated an increase in low-frequency/high-frequency (LF/HF) ratio in the CHF-INV compared with the sham-INV, which was normalized to sham levels by DNx. To assess whether this was due to a withdrawal of sympathetic tone or an increase in parasympathetic tone, the heart rate response was measured after an intravenous bolus of metoprolol or atropine. Bradycardia induced by intravenous metoprolol (indicative of cardiac sympathetic tone) was exacerbated in CHF-INV rabbits compared with sham-INV but was normalized in CHF-DNx. Conversely, the tachycardia in response to intravenous atropine (indicative of cardiac vagal tone) was not improved in CHF-DNx vs. CHF-INV animals. Renal DNx also prevented the increase in circulating plasma NE seen in CHF-INV rabbits. These results suggest renal DNx improves cardiac autonomic balance in CHF by a reduction of sympathetic tone.

Angiotensin II regulates ACE and ACE2 in neurons through p38 mitogen-activated protein kinase and extracellular signal-regulated kinase 1/2 signaling.

Brain ANG II plays an important role in modulating sympathetic function and homeostasis. The generation and degradation of ANG II are carried out, to a large extent, through the angiotensin-converting enzyme (ACE) and ACE2, respectively. In disease states, such as hypertension and chronic heart failure, central expression of ACE is upregulated and ACE2 is decreased in central sympathoregulatory neurons. In this study, we determined the expression of ACE and ACE2 in response to ANG II in a neuronal cell culture and the subsequent signaling mechanism(s) involved. A mouse catecholaminergic neuronal cell line (CATH.a) was treated with ANG II (30, 100, and 300 nM) for 24 h, and protein expression was determined by Western blot analysis. ANG II induced a significant dose-dependent increase in ACE and decrease in ACE2 mRNA and protein expression in CATH.a neurons. This effect was abolished by pretreatment of the cells with the p38 MAPK inhibitor SB-203580 (10 µM) 30 min before administration of ANG II or the ERK1/2 inhibitor U-0126 (10 µM). These data suggest that ANG II increases ACE and attenuates ACE2 expression in neurons via the ANG II type 1 receptor, p38 MAPK, and ERK1/2 signaling pathways.

Central Rho kinase inhibition restores baroreflex sensitivity and angiotensin II type 1 receptor protein imbalance in conscious rabbits with chronic heart failure.

The small GTPase RhoA and its associated kinase ROCKII are involved in vascular smooth muscle cell contraction and endothelial NO synthase mRNA destabilization. Overactivation of the RhoA/ROCKII pathway is implicated in several pathologies, including chronic heart failure (CHF), and may contribute to the enhanced sympathetic outflow seen in CHF as a result of decreased NO availability. Thus, we hypothesized that central ROCKII blockade would improve the sympathovagal imbalance in a pacing rabbit model of CHF in an NO-dependent manner. CHF was induced by rapid ventricular pacing and characterized by an ejection fraction of ≤45%. Animals were implanted with an intracerbroventricular cannula and osmotic minipump (rate, 1 µL/h) containing sterile saline, 1.5 µg/kg per day fasudil (Fas, a ROCKII inhibitor) for 4 days or Fas+100 µg/kg per day Nω-Nitro-l-arginine methyl ester hydrochloride, a NO synthase inhibitor. Arterial baroreflex control was assessed by intravenous infusion of sodium nitroprusside and phenylephrine. Fas infusion significantly lowered resting heart rate by decreasing sympathetic and increasing vagal tone. Furthermore, Fas improved baroreflex gain in CHF in an NO-dependent manner. In CHF Fas animals, the decrease in heart rate in response to intravenous metoprolol was similar to Sham and was reversed by Nω-Nitro-l-arginine methyl ester hydrochloride. Fas decreased angiotensin II type 1 receptor and phospho-ERM protein expression and increased endothelial NO synthase expression in the brain stem of CHF animals. These data strongly suggest that central ROCKII activation contributes to cardiac sympathoexcitation in the setting of CHF and that central Fas restores vagal and sympathetic tone in an NO-dependent manner. ROCKII may be a new central therapeutic target in the setting of CHF.