Submitted by Simone Souza (simonecgsouza@hotmail.com) on 2018-05-23T16:26:16Z No. of bitstreams: 1 DISS_2011_ Fábio Liberali Weissheimer.pdf: 1640556 bytes, checksum: e2f968f9fd0f610356f2cea91b142b03 (MD5) / Approved for entry into archive by Jordan (jordanbiblio@gmail.com) on 2018-05-24T17:17:32Z (GMT) No. of bitstreams: 1 DISS_2011_ Fábio Liberali Weissheimer.pdf: 1640556 bytes, checksum: e2f968f9fd0f610356f2cea91b142b03 (MD5) / Made available in DSpace on 2018-05-24T17:17:32Z (GMT). No. of bitstreams: 1 DISS_2011_ Fábio Liberali Weissheimer.pdf: 1640556 bytes, checksum: e2f968f9fd0f610356f2cea91b142b03 (MD5) Previous issue date: 2011-09-05 / A hipertensão arterial sistêmica (HA) é uma condição sistêmica que envolve alterações estruturais das artérias e do miocárdio, gerando níveis de pressão arterial (PA) sustentadamente elevados. De causalidade multifatorial é grande problema de saúde devido às altas prevalência, morbidade, mortalidade e custos. Estudos brasileiros sobre incidência de HA são raros. Estudo feito em 2008 em Porto Alegre-RS pontuou que 80% dos pré-hipertensos, entre 40 e 50 anos, terão HA em 10 anos. Desta forma, torna-se pertinente estudar a incidência da HA em Cuiabá-MT para que se obtenham informações técnico-científicas que subsidiem políticas de combate a HA. Objetivo: Analisar a incidência de HA e fatores associados em préhipertensos em Cuiabá-MT. Método: Coorte prospectivo de base populacional aprovado pela CEP/HUJM com acompanhamento em 6,8 anos de população fonte de 400 pré-hipertensos entre 2003 e 2010. Foram usadas estatísticas descritivas e inferenciais, risco relativo (IC 95%), teste de qui-quadrado de Pearson, p<0,05 e regressão múltipla de Poisson robusta. Resultados: População amostral de 171 indivíduos, 61,9% homens e 38,1% mulheres, idade média de 46,6 anos. Tempo de follow up de 6,8 anos. Média de anos de estudo de 9,5 anos. Renda média per capita de R$ 902,20. Foi observado no estudo que: 10,5% dos entrevistados admitiram consumir sal em excesso; 76,6% tomam café diariamente; 26,9% são sedentários; 13,4% fumam cigarros diariamente e 28,6% são obesos. A incidência de HA geral foi de 58,5% sendo que 86% destes estavam com PA descontrolada. Estratificando por exposição, a incidência de HA encontrada foi de 63,8% em indivíduos com renda per capita menor que 2 salários mínimos; 65,7% em indivíduos que consomem café diariamente; 71,7% nos sedentários e 77,6% nos obesos. Após regressão, mantiveram associadas ao desfecho HA às exposições (fatores de risco): obesos (p<0,001), tempo de assistir à televisão maior a 4 horas (p< 0,000), consumo de café diário (p< 0,005), renda menor que 2 salários mínimos (p< 0,041), número de moradores maior que 4 (p<0,047) e idade maior que 60 anos (p<0,000). Conclusão: O estudo demonstrou que há risco de 86% de um pré-hipertenso residente na área urbana de Cuiabá-MT desenvolver HA em 10 anos, e que a mesma está associada a fatores de risco conhecidos, em sua maioria modificáveis. Algumas associações sugerem maior estudo. Adoção de políticas de prevenção, tratamento e controle desta moléstia são necessárias. / The systemic arterial hypertension is a systemic condition which involves structural alterations of the artery and of the myocardium, generating continuously high levels of blood pressure. Of multifactorial causality, it is a great health issue due to its high prevalence, morbidity, mortality and costs. Brazilian researches on systemic arterial hypertension incidence are unusual. Research conducted in 2008 in Porto Alegre (RS) stated that 80% of the pre-hypertensive patients between 40 and 50 years will have systemic arterial hypertension in 10 years. Therefore, it is relevant to study the incidence of systemic arterial hypertension in Cuiabá (MT) in order to obtain technical-scientific information that subsidizes prevention policies against systemic arterial hypertension. Objective: To analyze the incidence of systemic arterial hypertension and associated factors on prehypertensive patients in Cuiabá (MT). Methods: Population-based prospective cohort approved by CEP/HUJM, with population of 400 pre-hypertensive patients watched for 6,8 years, from 2003 through 2010. Descriptive and inferential statistics were used, relative risk (Confidence Intervals - CI 95%), Pearson’s chi-square test, p<0,05 and multiple Poisson regression with robust variance. Results: Population sample of 171 patients, 61,9% men and 38,1% women, average of 46,6 years old. Follow-up time of 6,8 years. Schooling time of 9,5 years. Average per capita income of R$ 902,20. It was observed in this research that: 10,5% admit high level of salt consumption; 76,6% have daily coffee consumption; 26,9% are sedentary; 13,4% smoke cigarrettes; and 28,6% are obese. General systemic arterial hypertension incidence totaled 58,5%, from which 86% presented uncontrolled blood pressure. Stratified by exposition, the incidence of systemic arterial hypertension found was 63,8% in patients with per capita income below 2 minimum wages; 65,7% in patients that consume coffee daily; 71,7% in sedentary patients; and 77,6% in the obese. After regression, the following expositions remained associated (risk factors): obese (p<0,001), time spent watching TV higher than 4h (p< 0,000), daily coffee consumption (p< 0,005), income lower than 2 minimum wages (p< 0,041), number of inhabitants higher than 4 (p< 0,047) and age higher than 60 years old (p< 0,000). Conclusion: The research has shown that there is an 86% risk for a patient who is a resident of the urban area of Cuiabá (MT) to develop arterial hypertension in ten years, and this is associated to well known risk factors that are, in majority, modifiable. Some associations might demand a greater study. The adoption of prevention policies, treatment and control of this disease are required.

Le système endothéline (ET) est activé en condition d’hypertension pulmonaire (HTP). L’efficacité des antagonistes des récepteurs à l’ET a clairement été démontrée et a menée à l’approbation clinique de tels antagonistes dans le traitement de l’hypertension artérielle pulmonaire (HTAP). Toutefois, il existe présentement un important débat opposant l’utilisation d’un antagoniste sélectif des récepteur ETA à l’utilisation d’un antagoniste double ETA/ETB dans le traitement de cette pathologie. Bien que nous sachions que le système ET est activé et contribue à l’HTAP, les modifications locales de ce système induites par la pathologie, particulièrement au niveau des artères de résistance pulmonaires, demeurent inconnues. De plus, l’impact de ces modifications sur la réponse pharmacologique aux divers antagonistes des récepteurs à l’ET (sélectifs versus double) est d’une importance capitale. Ainsi, le but de la première étude de cette thèse était d’évaluer les modifications potentielles de la pharmacologie du système ET au niveau des artères de résistance pulmonaires induites par l’HTAP. Dans cette étude, nous avons démontré qu’en condition contrôle l’antagoniste sélectif ETA et l’antagoniste double n’ont eu aucun effet sur la réponse vasoconstrictrice à l’ET-1. Toutefois, en condition d’HTAP, les antagonistes sélectif et double ont tous deux été en mesure de réduire la vasoconstriction pulmonaire induite par l’ET-1. Une diminution importante de l’expression génique du récepteur ETB pourrait être à l’origine de cette modification du profil pharmacologique des antagonistes. Une meilleure compréhension des rôles joués par les récepteurs ETA et ETB au niveau des artères de résistance pulmonaires pourrait permettre l’optimisation des traitements de l’HTAP. Ainsi, le but de la deuxième étude était d’évaluer les effets d’un traitement antisens ex vivo dirigé contre l’ARNm des récepteurs ETA et ETB dans la vasoconstriction des artères de résistance pulmonaires induite par l’ET-1. Dans cette étude, nous avons démontré dans un premier temps que les récepteurs ETA et ETB pouvaient former des dimères au niveau des artères de résistance pulmonaires. De plus, nous avons observé qu’une réduction de l’expression protéique du R-ETA entraînait une potentialisation de la vasoconstriction ETB dépendante suggérant ainsi qu’en condition contrôle, le récepteur ETA aurait un effet inhibiteur sur la vasoconstriction pulmonaire induite par la stimulation du récepteur ETB. Les effets délétères de l’ET-1 sur la circulation pulmonaire sont bien connus, toutefois seules quelques études ont porté leur attention sur l’implication de l’ET-3 dans l’HTAP. Ainsi, le but de la troisième étude était d’évaluer l’implication potentielle de l’ET-3 dans l’HTAP. Dans cette étude, nous avons démontré qu’il était nécessaire en condition contrôle de bloquer simultanément les récepteurs ETA et ETB afin de réduire la réponse vasoconstrictrice pulmonaire à l’ET-3. En condition d’HTAP, nous avons observé une augmentation non-significative des concentrations plasmatiques d’ET-3 ainsi qu’une modification du profil pharmacologique des antagonistes des récepteurs à l’ET. En effet, l’utilisation de l’antagoniste sélectif ETA ou de l’antagoniste double était dans les deux cas en mesure de réduire la vasoconstriction pulmonaire à l’ET-3. Les résultats de ces trois études suggèrent qu’il est préférable d’utiliser un antagoniste double dans le traitement de l’HTAP. En effet, (1) en condition d’HTAP, l’utilisation d’un antagoniste double est aussi efficace que l’utilisation d’un antagoniste sélectif ETA; (2) les récepteurs ETA et ETB peuvent former des dimères au niveau des artères de résistance pulmonaires et (3) le récepteur ETB joue un rôle prédominant dans la vasoconstriction pulmonaire, il semble donc essentiel de bloquer simultanément les récepteurs ETA et ETB afin d’inhiber la réponse vasoconstrictrice induite par l’ET. Mots-clés: endothéline-1, endothéline-3, artère de résistance pulmonaire, récepteur vasculaire, antagoniste des récepteurs à l’ET, dimérisation, phosphorothioate, hypertension artérielle pulmonaire / The endothelin (ET) system is activated in pulmonary arterial hypertension (PAH); indeed, increased plasma levels of ET-1 were detected in patients with various forms of PAH and in various experimental models. The therapeutic value of pharmacological blockade of ET receptors has been demonstrated in various animal models and led to the current approval and continued development of these drugs for the therapy of human PAH. Whether the net effect of either selective ETA receptor blockade or combined ETA/ETB receptor blockade provides greater therapeutic benefit remains a subject of debate. Although the ET system contributes to PAH, we currently incompletely comprehend which local modifications of this system occur as a consequence of PAH, particularly in small resistance arteries, and how this could affect the pharmacological response to ET receptor antagonists. The purpose of the first study was therefore to evaluate potential modifications of the pharmacology of the ET system in rat pulmonary resistance arteries from monocrotaline-induced PAH. Our results reveal striking changes in pulmonary vasculature sensitivity to ET receptor antagonism in PAH that may be related to a reduction in ETB receptor expression. A better understanding of the exact role played by both ETA and ETB receptors on pulmonary resistance arteries might contribute to optimization of PAH treatments. Therefore the aim of the second study was to clarify the role played by both ETA and ETB receptors in ET-1 induced pulmonary vasoconstriction using an antisense (AS) oligonucleotide ex vivo treatment. In this study we have demonstrated that ETA and ETB receptors can form heterodimers in pulmonary resistance arteries. Furthermore, suppression of ETA receptors potentiated the response to ET-1 suggesting that in control condition the ETA receptor has an inhibitory action on the ET-1 induced pulmonary vasoconstriction induced by the stimulation of the ETB receptor. Although the deleterious effects of ET-1 on the pulmonary circulation are well established, only a few studies have focused on ET-3 in PAH. Therefore, the purpose of the last study was to evaluate the potential implication of ET-3 in MCT-induced PAH and evaluate the roles of ETA and ETB receptors on ET-3-induced pulmonary vascular reactivity. In control condition, the use of a combination of both ETA and ETB receptor antagonists is necessary to reduce the ET-3 induced pulmonary vasoconstriction. In PAH, we found an increased ET-3 plasma levels and a modification of the pharmacological profile of ET receptor antagonists. Indeed, the use of either the ETA receptor antagonist or the dual antagonist was able to reduce the ET-3 response. The results from these three studies suggest that it is preferable to use a dual antagonist in the treatment of PAH. Indeed, (1) in PAH the use of a dual antagonist is as effective as the use of a selective ETA receptor antagonist (2) ETA and ETB receptors can form heterodimers in pulmonary resistance arteries and (3) ETB receptor plays an important role in the ET-1 induced pulmonary vasoconstriction, suggesting that it is necessary to block both receptors to reduce the ET-1 induced pulmonary vasoconstriction. Keywords: endothelin-1, endothelin-3, pulmonary resistance artery, receptor, endothelin receptor antagonist, dimerisation, phosphorothioate pulmonary arterial hypertension

Des lacunes existent au niveau des connaissances concernant les modifications cardiovasculaires manifestées avant l’établissement d’obésité et en absence d’hyperlipidémie. Dans cette optique, la présente étude a testé l'hypothèse générale qui stipule que l’administration d’une diète riche en gras pour une période de 8 semaines chez les rats femelles influence négativement la fonction et le remodelage cardiaque, avant le développement de l’obésité et en absence d’hyperlipidémie et d’hyperglycémie. Afin de répondre à cette problématique, des rats femelles Sprague-Dawley ont été assignés à une diète standard (SD; 12,5% lipides, kcal) ou riche en gras (HF; 42% lipides, kcal) pour une période de 8 semaines. Cette durée était insuffisante pour induire le développement d’une dyslipidémie ou une augmentation significative de la masse corporelle chez les animaux HF(329±14g) comparativement aux rates SD (300±10g). Toutefois, une hypertension artérielle s’est développée chez les rates HF (130±4 vs 108±6 mmHg, p<0,05), accompagnée d’une altération des relaxations aortiques dépendantes de l’endothélium (relaxation maximale : 22±5% versus 53±8%, pour les animaux HF et SD respectivement, p<0,05). L’administration orale chronique de l’antioxydant resvératrol (RES; 20 mg·kg-1·jr-1) a prévenu le développement de ces altérations pathologiques, attestant d’une implication du stress oxydant. Au niveau cardiaque, le RES n’a toutefois pas inhibé le développement de fibrose périvasculaire secondaire à l’administration de la diète riche en gras. Suite à une insulte d’ischémie-reperfusion, la taille (SD : 0,29±0,09 versus HF : 0,32±0,13 cm), l’épaisseur (SD : 0,05±0,02 versus HF : 0,06±0,01 cm) et le contenu en collagène α1 type 1 (SD : 0,21±0,04 versus HF : 0,20±0,04 unités arbitraires/mm2) de la cicatrice du coeur infarci des rats HF étaient comparables au coeur infarci des rats SD. Malgré ces similitudes, le taux de décès était significativement (p<0,05) plus élevé chez les rats HF (56%) comparativement aux rats SD (5%). L’approche par électrophysiologie a démontré que l’administration de la diète riche en gras était associée à une augmentation (p<0,05) du nombre d’extrasystoles ventriculaires induites. Cette élévation de l’incidence était associé à une hyperinnervation sympathique fonctionnelle, tel que démontré par une élévation (p<0,05) de la densité des fibres neurofilament-M (HF : 2830±250 versus SD : 2020±260 μm2/mm2) et de la protéine de l’hydroxylase de la tyrosine. La fonctionnalité des jonctions intercellulaires était également atteinte, caractérisée par une latéralisation et internalisation de connexine 43 ainsi qu’une diminution de l’expression de connexine 40 au niveau des disques intercalaires. Ainsi, avant l’établissement de l’obésité et d’une dyslipidémie, les rats femelles modestement hypertendus présentent un phénotype arythmogénique cardiaque en partie dû à une hyperinnervation sympathique et une expression altérée concomitante de la distribution et de l’expression des jonctions intercellulaires. L’absence de symptômes cliniques d’obésité dans la présente étude ne fournit aucun indice au clinicien quant à la susceptibilité accrue aux arythmies ventriculaires. Ainsi, en présence d’une hypertension artérielle modérée chez un patient non-obèse, une mesure de l’activité sympathique par la quantification des niveaux circulants de catécholamines pourrait être bénéfique afin de détecter les patients à risque de mort subite. / Knowledge is insufficient regarding cardiovascular modifications occurring prior to the development of overt obesity and dyslipidemia. In this regard, the present project aimed at testing the hypothesis stipulating that the administration of a high fat diet for an 8-week period in female rats can adversely influence cardiac function and remodeling prior to the development of overt obesity, and in the absence of hyperlipidemia and hyperglycaemia. To directly examine these issues, normal female Sprague-Dawley rats were fed a standard (SD; 12.5% lipid, kcal) or a high-fat diet (HF; 42% lipids, kcal) for 8 weeks. This regimen was insufficient to induce a significant gain in body mass in HF rats (329±14g) as compared to SD rats (300±10g), or any variation in the lipid profile. By contrast, systemic arterial hypertension developed in high fat fed rats (130±4mmHg versus SD, 108±6mmHg, p<0.05), additionally to a significant decrease in acetylcholine-mediated maximal relaxation of isolated aortic rings (HF, 22±5%) compared to rats fed a standard diet (53±8%, p<0.05). Chronic oral administration of the antioxidant resveratrol (RES; 20 mg·kg-1·d-1) prevented the development of both pathological alterations, attesting to the implication of oxidative stress. However, it failed to attenuate the perivascular fibrosis that developed following the administration of the high-fat diet. Following ischemia/reperfusion injury, scar length (SD, 0.29±0.09 versus HF, 0.32±0.13 cm), thickness (SD, 0.05±0.02 versus HF, 0.06±0.01 cm) and collagen α1 type 1 content (SD, 0.21±0.04 versus HF, 0.20±0.04 arbitrary units/mm2) in the infarcted heart of rats fed a high fat diet were similar to infarcted normal rats. Despite these findings, the rate of death was significantly increased (p<0.05) in female rats fed a high fat diet (56%) compared to rats fed a standard diet (5%). An electrophysiology approach revealed that normal female rats fed a high fat diet had an increased incidence (p<0.05) of induced ventricular extrasystoles. In addition, these hearts presented a functional sympathetic hyperinnervation, as reflected by the increased density of neurofilament-M immunoreactive fibres (SD, 2020±260 versus HF, 2830±250 μm2/mm2; p<0.05) and increased protein expression of tyrosine hydroxylase. The gap junction function was also impaired, characterized by lateralization and internalization of connexine 43, and a decreased expression of connexine 40 in intercalated discs of rats fed a high fat diet. Thus, prior to the development of overt obesity and dyslipidemia, female rats with modest hypertension exhibit an arrhythmogenic cardiac phenotype due in part to sympathetic hyperinnervation and a concomitant aberrant pattern of gap junctional protein expression and distribution. The lack of significant clinical manifestations of obesity in the present study does not enable clinicians to suspect the increased susceptibility to ventricular arrhythmias. Hence, in presence of modest hypertension in a non-obese patient, evaluation of the sympathetic activity by the assessment of circulating catecholamine could be helpful in detecting patients at high risk for sudden death.

Les kinines agissent sur deux types de récepteurs couplés aux protéines G, nommés B1 et B2, lesquels jouent un rôle important dans le contrôle cardiovasculaire, la nociception et l’inflammation. Nous considérons l’hypothèse que le récepteur B1 des kinines est induit et contribue aux complications diabétiques, incluant l’hypertension artérielle, les polyneuropathies sensorielles, l’augmentation du stress oxydatif vasculaire, l’inflammation vasculaire et l’obésité chez le rat traité au D-glucose (10% dans l’eau de boisson) pendant 8 ou 12 semaines. Dans ce modèle de résistance à l’insuline, nous avons évalué les effets d’un traitement pharmacologique d’une semaine avec un antagoniste du récepteur B1 des kinines, le SSR240612 (10 mg/kg/jr). Les résultats montrent que le SSR240612 renverse l’hypertension, l’allodynie tactile et au froid, la production de l’anion superoxyde et la surexpression de plusieurs marqueurs inflammatoires dans l’aorte (iNOS, IL-1β, macrophage (CD68, CD11), ICAM-1, E-selectine, MIF ainsi que le B1R) et dans les adipocytes (iNOS, IL-1β, TNF-α et macrophage CD68). De plus, le SSR240612 corrige la résistance à l’insuline, les anomalies du profil lipidique plasmatique et le gain de poids et de masse adipeuse. Ces données supportent l’implication des kinines dans les complications diabétiques dans un modèle animal de résistance à l’insuline et suggèrent que le récepteur B1 est une cible thérapeutique potentielle dans le diabète et l’obésité. / Kinins act on two G-protein-coupled receptors, denoted as B1 and B2, and play an important role in cardiovascular regulation, nociception and inflammation. We have considered the hypothesis that kinin B1 receptor is upregulated and involved in diabetic complications, notably hypertension, pain sensory neuropathy, the oxidative stress in the vasculature, vascular inflammation, insulin resistance and obesity in rats treated for 8 or 12 weeks with D-glucose (10% of glucose in their drinking water). In this model of insulin resistance, we assessed the effects of one-week treatment with SSR240612 (10 mg/kg/day), a selective kinin B1 receptor antagonist. Data show that SSR240612 reverses high blood pressure, tactile and cold allodynia, the production of oxidative stress (superoxyde anion) in the aorta, the overexpression of iNOS, IL-1β, macrophage (CD68, CD11), ICAM-1, E-selectine, MIF and B1R in the aorta and iNOS, IL-1β, TNF-α and macrophage (CD68) in adipocytes. Moreover, SSR240612 reverses insulin resistance, plasma fatty acids composition changes and body and tissue fat gain. These data support a key role for kinins in diabetic complications in a rat model of insulin resistance and suggest that kinin B1 receptor is a promising therapeutic target in diabetes and obesity.

Made available in DSpace on 2011-05-04T12:36:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2010 / Em todo mundo há mudança no perfil epidemiológico da população no sentidode aumento da prevalência de doenças crônico-degenerativas. No Brasil, a hipertensão arterial (HTA) e diabetes mellitus (DM) estão entre os agravos cuja prevalência tem aumentado além de serem fatores de risco para doenças cerebrovasculares e doenças cardíacas isquêmicas, que são as principais causas de mortalidade na população. Por serem tratamentos longos e que, em geral, uma vez instaurados, persistem por toda avida do paciente, a adesão ao tratamento é imprescindível para que o indivíduo mantenha a qualidade de vida e evite ou adie as complicações da doença. Entretanto, a não adesão ao tratamento de doenças crônicas é um problema de saúde pública de extensão mundial, acarretando impactos negativos na saúde do indivíduo e problemas econômicos para o sistema de saúde, pois em muitos casos, a pouca adesão resultará em maiores custos com hospitalizações, que incluem o tratamento de complicações de longo prazo. Desta forma, na avaliação dos programas de saúde pública, é conveniente examinar a adesão ao tratamento que é oferecido pela rede assistencial. Por isso, um dos objetivos da pesquisa de avaliação do programa Remédio em Casa da Prefeitura do Rio de Janeiro era avaliar o nível de adesão ao tratamento de hipertensos e diabéticos. Para tanto, procurou-se utilizar um questionário que avaliasse a adesão sob a perspectiva da OMS, a qual considera limitado restringir a adesão ao grau de seguimento das instruções médicas e que defende o papel ativo do indivíduo no seu tratamento. Como o questionário cubano MBG desenvolvido e validado por Alfonso et al. (2008) atende essas considerações, decidiu-se traduzi-lo para o português através de um processo formal de adaptação transcultural com vistas a ser utilizado na pesquisa de avaliação do programa Remédio em Casa da Prefeitura do Rio de Janeiro. Este processo seguiu a proposta de operacionalização de Reichenheim e Moraes (2007), cujas etapas são baseadas na avaliação de algum tipo de equivalência. Assim, foram feitos pré-testes e um piloto com a versão traduzida do instrumento. Com os resultados do piloto, foram analisadas as características psicométrica de confiabilidade do instrumento, através da investigação da consistência interna e da estabilidade teste-reteste. Com alfa de Cronbach do instrumento superior a 0,70 (0,78 no teste e 0,79 no re-teste) e um coeficiente de correlação intraclasse para o total do instrumento de 0,81 (indicando oncordância quase perfeita ), é possível afirmar que bons níveis de confiabilidade foram obtidos e que o instrumento é capaz de medir de modo reprodutível a adesão ao tratamento. / Everywhere there is change in the epidemiological pattern of the population towards an increased prevalence of chronic degenerative diseases. In Brazil, arterial hypertension (HT) and diabetes mellitus (DM) are among the diseases whose prevalence has increased, besides they are risk factors for cerebrovascular disease and ischemic heart diseases, which are the main causes of mortality. Because of their long treatments that, in general, once initiated, persist throughout the patient's life, treatment adherence is essential for individuals to maintain their quality of life and avoid or delay the complications of the diseases. However, non-adherence to treatment of chronic diseases is a public health problem of global extent, causing negative impacts on individuals’ health and economic problems for the health system, because in many cases, noncompliance will result in higher costs with hospitalizations, which include the treatment of long-term complications. Thus, in assessing public health programs, it is necessary to examine adherence to the treatment offered by health care network. Therefore, one objective of the “Remédio em Casa” program evaluation in the district of Rio de Janeiro was to assess the level of adherence to treatment of arterial hypertension or diabetes mellitus. We looked for a questionnaire to assess adherence from the perspective of WHO, which considers limited defining adherence as “the extent to which the patient follows medical instructions”, and defends the individual's active role in your treatment. As the Cuban MBG questionnaire developed and validated by Alfonso et al. (2008) addresses these considerations, we decided to translate it into Portuguese through a formal process of cultural adaptation in order to be used in the research “Remédio em Casa” program evaluation in the district of Rio de Janeiro. This process has followed the Reichenheim and Moraes’ (2007) operational framework, whose steps are based on the evaluation of some kind of equivalence. Thus, pre-tests and a pilot study with the translated version of the instrument were made. We analyzed the psychometric reliability of the instrument with the results of the pilot study through investigation of internal consistency and test-retest stability. The alpha Cronbach instrument exceeded 0.70 (0.78 and 0.79 in the test re-test) and the intraclass correlation coefficient for the total instrument was 0.81 (indicating agreement "almost perfect"), so it’s possible to say that good levels of reliability were obtained and that the instrument is able to measure reproducibly adherence to treatment.

Evidências recentes sugerem que as doenças periodontais podem desempenhar um papel relevante na etiologia e patogênese de doenças cardiovasculares e hipertensão arterial. A resposta inflamatória, com conseqüente elevação de marcadores sistêmicos como proteína C-reativa, fibrinogênio e interleucina-6, e a disfunção endotelial, podem ser os responsáveis por essa associação. Alguns estudos têm relatado maiores níveis pressóricos, maior massa ventricular esquerda e disfunção endotelial em pacientes com doenças periodontais. Ao mesmo tempo, estudos clínicos vêm mostrando que a terapia periodontal pode levar à redução dos níveis plasmáticos dos marcadores de inflamação e redução do risco cardiovascular. O presente estudo teve como objetivo avaliar os efeitos da terapia periodontal não-cirúrgica em 26 pacientes (idade média de 53.68.0 anos) hipertensos refratários. Foram avaliados marcadores plasmáticos de inflamação (proteína C-reativa, fibrinogênio e interleucina-6), pressão arterial sistólica e diastólica, massa ventricular esquerda e rigidez arterial. A terapia periodontal foi eficaz na redução da média de todos os marcadores de risco cardiovascular avaliados. Os níveis de proteína C-reativa baixaram 0.7mg/dl 6 meses após a terapia periodontal, os de IL-6, 1.6pg/dl e os de fibrinogênio 55.3mg/dl (p<0.01). A pressão arterial sistólica apresentou redução média de 16.7mmHg e a diastólica de 9.6mmHg. A massa ventricular esquerda diminuiu em média 12.9g e a velocidade da onda de pulso, um marcador de rigidez arterial, e consequentemente de disfunção endotelial, apresentou redução de seus valores médios de 0.9m/s (p<0.01). Dessa forma, conclui-se que a terapia periodontal foi eficaz na redução dos níveis de proteína C-reativa, interleucina-6, fibrinogênio, pressão arterial, massa ventricular esquerda e rigidez arterial. / Recent evidences suggest that periodontal diseases may play a relevant role in the etiology and pathogenesis of cardiovascular diseases and hypertension. The inflammatory response, and the consequent elevation of systemic markers such as C-reactive protein, fibrinogen and interleukin-6, and endothelial dysfunction, may be responsible for this association. Some studies have reported higher blood pressure levels, left ventricle mass and endothelial dysfunction in patients presenting periodontal diseases. At the same time, clinical trials have been showing that periodontal therapy can lead to the reduction of plasmatic levels of inflammatory markers and reduction of the cardiovascular risk. The present study aims to evaluate the effects of non-surgical periodontal therapy in 26 patients (mean age: 53.68.0 years old) diagnosed as having refractory hypertension. The study measured plasmatic markers of inflammation (C-reactive protein, fibrinogen and interleukin-6), systolic and diastolic blood pressure, left ventricle mass and arterial stiffness. Periodontal therapy was effective in reducing all cardiovascular risk markers evaluated. The levels of C-reactive protein lowered 0.7mg/dl 6 months after periodontal therapy, the IL-6 levels, 1.6pg/dl and fibrinogen levels 55.3mg/dl (p<0.01). Systolic blood pressure lowered 16.7mmHg and diastolic 9.6mmHg (means). Left ventricle mass lowered 12.9g (means) and pulse wave velocity, a marker of arterial stiffness, and consequently endothelial dysfunction, presented reduction of 0.9m/s (means) (p<0.01). So, the study conclusion is that periodontal therapy was effective in reducing levels of C-reactive protein, interleukin-6, fibrinogen, blood pressure, left ventricle mass and arterial stiffness.

Arterial stiffness represented by carotid-femoral pulse wave velocity (PWV) is considered to be an independent cardiovascular risk factor. This study was focused on large artery properties investigation in specific forms of hypertension using applanation tonometer Sphygmocor (Atcor Medical). PWV was significantly higher in resistant hypertension patients when compared to moderate essential hypertension (EH) patients. This difference appears to be independent of clinical blood pressure (BP). Night-time BP appears to be a more accurate predictor of PWV in EH. In another study we demonstrated that primary hyperparathyroidism (PH) (both hypertensive or non-hypertensive forms) might be associated with higher PWV when compared to EH patients or to normotensive controls and that this difference is independent of age and clinical BP. Neither calcium serum level, nor parathyroid hormone has been associated with PWV. Specific treatment by parathyroidectomy (PTX) seems to be beneficial for PWV decrease, which might be mainly determined by improved BP control after surgery. Since PTX indications for asymptomatic forms of PH have been discussed, our data suggest the potential benefit to the extent of subclinical organ damage after surgical treatment in these patients. Similarly, we prooved higher PWV in...

Hypertension is a major risk factor for cardiovascular (CV) disease, and patients with primary aldosteronism (PA) - the most common endocrine cause of hypertension - have a higher incidence of CV complications. The aim of this study was to evaluate the incidence of metabolic differences and organ complications - kidney, heart and blood vessels damage in patients with essential hypertension (EH), PA and its most common forms - idiopathic hyperaldosteronism (IHA) and aldosterone-producing adenoma (APA). We found a higher incidence of metabolic syndrome and a higher incidence of metabolic abnormalities in IHA compared to APA - higher prevalence of metabolic syndrome, higher levels of triglycerides and lower levels of HDL cholesterol and thereby a higher cardiometabolic risk. Metabolic profile of patients with IHA is similar to EH in contrast to APA. Arterial stiffness was expressed as pulse wave velocity (PWV), in central arteries as carotid-femoral PWV and at peripheral level as femoral-ankle PWV. Patients with PA with comparable levels of blood pressure (BP) have higher stiffness of central elastic and peripheral muscular arteries than patients with EH. The main predictor of impaired peripheral arterial stiffness is the plasma aldosterone level. Patients with IHA have higher central arterial...

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Estudos caracterizaram o envolvimento da PDI na modulação da geração de EROs pela Nox1 como moduladores da migração de células do músculo liso vascular (VSMC) mediados por fatores de crescimento derivados de plaqueta (PDGF). Outros estudos vêm demonstrando o envolvimento do fator de crescimento epidermal (EGFR) no remodelamento vascular, após a transativação via Angiotensina II. Entretanto o papel da PDI na ativação do EGFR via Nox1 na hipertensão arterial ainda permanece desconhecido. Objetivo foi caracterizar o papel da PDI na expressão de Nox1 dependente do EGFR durante o desenvolvimento da hipertensão arterial. Resultados demonstram um aumento da expressão de HB-EGF e ativação de ERK 1/2 na aorta de animais SHR com 8 semanas e 12 semanas de idade, e no plasma de animais SHR com 12 semanas. Ainda, a OvxPDI acarretou em um aumento na expressão gênica de Nox-1 tanto na OVXPDI quanto na forma OvxPDIMUT. Resultados mostram um novo papel da PDI na expressão gênica de Nox-1 via EGFR e a participação desta tiol oxido redutase na gênese da hipertensão arterial. / Studies characterizing the involvement of PDI in the modulation of ROS by Nox1 as modulators of cell migration of vascular smooth muscle (VSMC) mediated by growth factors derived from platelets (PDGF). Other studies have demonstrated the involvement of the epidermal growth factor receptor (EGFR) on vascular remodeling after transactivation via Angiotensin II. However the role of PDI in the activation of EGFR via Nox1 in hypertension remains unknown. Objective was to characterize the role of PDI in Nox1 dependent EGFR expression during the development of hypertension. Results show an increase of HB-EGF expression and ERK 1/2 activation in the aortic SHR at 8 weeks and 12 weeks of age, and plasma SHR at 12 weeks. Still, the OvxPDI resulted in an increase in gene expression of Nox-1 both in OVXPDI and in OvxPDIMUT way. Results show a new role of PDI in gene expression of Nox-1 via EGFR and the participation of this thiol reductase oxide in the pathogenesis of hypertension.