Self-monitoring, lowered arousal training (i.e., biofeedback and relaxation training) and maintenance follow-up appeared to contribute to effective treatment of hypertension. Cognitive therapy, while effective in treatment of some stress-related disorders, has not been studied as a specific treatment component for hypertension. The present study explored the use of cognitive therapy as a treatment variable to reduce blood pressure in hypertensive persons. The effectiveness of a multi-element treatment including cognitive therapy, blood-pressure biofeedback, and relaxation training was also assessed. Self-monitoring and maintenance training were included as a part of each treatment process.

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / A hipertensão essencial humana, bem como a hipertensão desenvolvida em Ratos Espontaneamente Hipertensos (SHR), são caracterizadas pelo desenvolvimento de Pressão Arterial (PA) elevada na medida em que a idade avança, sem identificação da causa primária. Está bem estabelecido que este modelo animal apresenta estresse oxidativo (EOx) concomitante a hipertensão. O mecanismo pelo qual o antioxidante reduz a pressão não está claro, por essa razão, é necessário avaliar o comportamento destas enzimas envolvidas na homeostase da PA. Ratos Wistar-Kyoto (WKY) e SHR machos receberam ácido ascórbico, 200 mg / kg / dia por sonda orogástrica durante cinco semanas. A PA, a Hipertrofia Ventricular Esquerda (HVE), o Sistema Renina-Angiotensina (SRA), o Peptídeo Natriurético Atrial (ANP) e o EOx foram comparados entre os grupos por pletismografia, estereologia, microscopia confocal de varrimento a laser, microscopia eletrônica de transmissão, western blotting e análise do RT-qPCR. Os SHR tratados com ácido ascórbico reduziram a PA e a HVE. Além disso, as enzimas envolvidas na homeostase da PA, a renina e a Enzima Conversora de Angiotensina (ECA) normalizaram-se, bem como os Receptores tipo 1 de Angiotensina II (AT1). A grande quantidade de grânulos de ANP no grupo SHR foi reduzida pelo tratamento com ácido ascórbico. O balanço oxidativo foi restabelecido nos SHR tratados com este antioxidante. O EOx nos SHR eleva os níveis de renina e de PA. Estas espécies reativas de oxigênio podem ser envolvidas no mecanismo de sinalização para aumentar a expressão de ANP nos miócitos atriais. Estes dados também mostram que o tratamento com o antioxidante (vitamin C) reduz o EOx e normaliza a PA ao menos parcialmente pela redução de taxas de renina. / The essential hypertension, as well as the Spontaneously Hypertensive Rat (SHR), is characterized by the development of high BP (BP) with advancing age, with no identified primary cause. It is well established that this animal model presents OxS concomitant hypertension. The mechanism, by which the antioxidant reduces the pressure, is not clear, for this reason, it is necessary to evaluate the behavior of enzymes involved in the homeostasis of BP. Male Wistar-Kyoto (WKY) rats and SHR received ascorbic acid, 200 mg / kg / day by orogastric gavage with lasted five weeks. The BP, Left Ventricular Hypertrophy (LVH), renin-angiotensin system (RAS), Atrial Natriuretic Peptide (ANP) and OxS results have been extensively compared among groups by plethysmography, stereology, confocal laser scanning microscopy, transmission electron microscopy, western blotting and RT-qPCR analysis. The SHR treated with ascorbic acid reduced BP and LVH. Also, the enzymes involved in the homeostasis of BP, renin and Angiotensin Converting Enzyme (ACE) normalized, as well as Angiotensin II type 1 receptor (AT1R). The large amount of ANP granules in SHR group was reduced by treatment with ascorbic acid. Oxidative balance was reestablished in SHR treated with this antioxidant. OxS in SHR elevates renin levels and BP. These reactive oxygen species may be involved in the signaling mechanism for increased expression in ANP atrial myocytes. These data also show that treatment with antioxidant (vitamin C) reduces OxS and normalizes BP at least partly by reducing rates of renin.

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / A hipertensão essencial humana, bem como a hipertensão desenvolvida em Ratos Espontaneamente Hipertensos (SHR), são caracterizadas pelo desenvolvimento de Pressão Arterial (PA) elevada na medida em que a idade avança, sem identificação da causa primária. Está bem estabelecido que este modelo animal apresenta estresse oxidativo (EOx) concomitante a hipertensão. O mecanismo pelo qual o antioxidante reduz a pressão não está claro, por essa razão, é necessário avaliar o comportamento destas enzimas envolvidas na homeostase da PA. Ratos Wistar-Kyoto (WKY) e SHR machos receberam ácido ascórbico, 200 mg / kg / dia por sonda orogástrica durante cinco semanas. A PA, a Hipertrofia Ventricular Esquerda (HVE), o Sistema Renina-Angiotensina (SRA), o Peptídeo Natriurético Atrial (ANP) e o EOx foram comparados entre os grupos por pletismografia, estereologia, microscopia confocal de varrimento a laser, microscopia eletrônica de transmissão, western blotting e análise do RT-qPCR. Os SHR tratados com ácido ascórbico reduziram a PA e a HVE. Além disso, as enzimas envolvidas na homeostase da PA, a renina e a Enzima Conversora de Angiotensina (ECA) normalizaram-se, bem como os Receptores tipo 1 de Angiotensina II (AT1). A grande quantidade de grânulos de ANP no grupo SHR foi reduzida pelo tratamento com ácido ascórbico. O balanço oxidativo foi restabelecido nos SHR tratados com este antioxidante. O EOx nos SHR eleva os níveis de renina e de PA. Estas espécies reativas de oxigênio podem ser envolvidas no mecanismo de sinalização para aumentar a expressão de ANP nos miócitos atriais. Estes dados também mostram que o tratamento com o antioxidante (vitamin C) reduz o EOx e normaliza a PA ao menos parcialmente pela redução de taxas de renina. / The essential hypertension, as well as the Spontaneously Hypertensive Rat (SHR), is characterized by the development of high BP (BP) with advancing age, with no identified primary cause. It is well established that this animal model presents OxS concomitant hypertension. The mechanism, by which the antioxidant reduces the pressure, is not clear, for this reason, it is necessary to evaluate the behavior of enzymes involved in the homeostasis of BP. Male Wistar-Kyoto (WKY) rats and SHR received ascorbic acid, 200 mg / kg / day by orogastric gavage with lasted five weeks. The BP, Left Ventricular Hypertrophy (LVH), renin-angiotensin system (RAS), Atrial Natriuretic Peptide (ANP) and OxS results have been extensively compared among groups by plethysmography, stereology, confocal laser scanning microscopy, transmission electron microscopy, western blotting and RT-qPCR analysis. The SHR treated with ascorbic acid reduced BP and LVH. Also, the enzymes involved in the homeostasis of BP, renin and Angiotensin Converting Enzyme (ACE) normalized, as well as Angiotensin II type 1 receptor (AT1R). The large amount of ANP granules in SHR group was reduced by treatment with ascorbic acid. Oxidative balance was reestablished in SHR treated with this antioxidant. OxS in SHR elevates renin levels and BP. These reactive oxygen species may be involved in the signaling mechanism for increased expression in ANP atrial myocytes. These data also show that treatment with antioxidant (vitamin C) reduces OxS and normalizes BP at least partly by reducing rates of renin.

I Sverige har cirka 2 miljoner människor diagnosen hypertoni och det är den folksjukdom som ligger bakom cirka 30 000 fall av stroke och lika många hjärtinfarkter varje år. En ökning av personer med sjukdomen hypertoni ses i världen vilket beror på att världens befolkning och den åldrande befolkningen ökar. Hypertoni beror på funktionella kärlförändringar i artärväggen som leder till en stelhet. Denna stelhet är resultatet av flera faktorer såsom förhöjda blodfetter, rökning, diabetes, åldern, alkoholvanor och övrig livsstil. Vid hypertoni är risken stor för att utveckla kardiovaskulär sjukdom som stroke, hjärtsvikt, kranskärls- och njursjukdom. Hypertoni är även den enskilt största behandlingsbara riskfaktorn för kardiovaskulär sjukdom. Förändring av livsstil är grunden i behandlingen, men flertalet individer behöver också behandlas med läkemedel. För att uppnå detta krävs hälsokompetens hos patienten och ett personcentrerat arbetssätt hos vårdpersonal   Syfte: Syftet med studien var att undersöka patientens hälsokompetens kring risken att utveckla kardiovaskulär sjukdom vid ohälsosam livsstil och primär hypertoni. En frågeställning skapades för att se om det fanns skillnader mellan könen.   Metod: Metoden var en empirisk deskriptiv icke experimentell tvärsnittsstudie med kvantitativ ansats. Författarna valde att göra en enkätstudie på 50 stycken patienter som fått diagnosen primär hypertoni mellan åren 2014-2017 på en vårdcentral i södra Sverige.   Resultat: Det framkommer att en viss del av deltagarna får information om livsstilsförändringar gällande kostvanor, rökning, alkoholvanor och fysisk aktivitet och dess betydelse vid diagnosen hypertoni. Det framkommer även att de gjort förändringar utifrån detta. Dock är det långt ifrån alla som får information och gör ändringar och skillnader mellan män och kvinnor kan ses.   Slutsats: Ett medvetandegörande om patientens hälsokompetens och ett personcentrerat förhållningssätt hos vårdpersonal i det primärpreventiva arbetet med livsstilsförändringar anser författarna är av största vikt. Detta för att hjälpa patienten till egenvård av sin primära hypertoni, vilket på sikt minskar risken för kardiovaskulär sjukdom, främjar hälsa och samhällets ekonomi. / Approximately 2 million people in Sweden are diagnosed with hypertension, which is a public health disease that is estimated to cause 30, 000 cases of stroke and myocardial infarction every year. An overall growing and aging population in the world is the cause of the increase in the numbers of people diagnosed with hypertension in the world. Hypertension is caused by functional changes in the arterial wall which causes a stiffness in the vessel. This stiffness is a result of factors such as dyslipidemia, smoking, diabetes, age, consumption of alcohol and other lifestyle factors. People with hypertension have an increased risk of developing cardiovascular diseases such as stroke, heart failure, coronary arterial disease and kidney disease. Hypertension is also the greatest treatable risk factor for cardiovascular disease. Lifestyle changes is the cornerstone in the treatment of hypertension, however many individuals may also need drug therapy. For the individual to achieve lifestyle changes, the patient needs a high level of health literacy and a person centred approach from health care professionals are needed   Aim: The aim of this study was to investigate the patient’s health literacy relating to the risk of developing cardiovascular disease with an unhealthy lifestyle in combination with essential hypertension. A question formulation was constructed as a compliment to the aim of the study with the purpose of identifying possible differences between the sexes.   Method: The method was an empirical descriptive non experimental cross-sectional study with a quantitative approach. The authors choose to conduct the study by handing out 50 questionnaires to patients diagnosed with essential hypertension between the years 2014-2017 at a public health office in southern part of Sweden.   Result: Participants received information regarding lifestyle changes such as eating habits, smoking, alcohol consumption and physical activity and their importance when diagnosed with hypertension. The results also showed that the participants made changes regarding this. However not all participants got information or made changes and a differences between men and women could be seen.                                                    Conclusion: Making health care professionals conscious of the patient’s health literacy while maintaining a person centred approach in the primary preventive care, which is focusing on lifestyle changes, is of utmost importance. It is essential to enable the patient’s self care regarding their essential hypertension, which further reduces the risk to develop cardiovascular disease, promotes health and benefits the economy of the society.

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / A insuficiência renal crônica (IRC) e a hipertensão arterial sistêmica (HAS) são patologias com alta morbidade e mortalidade, consumindo grandes verbas de saúde pública. A disfunção endotelial presente tanto na IRC, como na hipertensão, contribui para a manutenção de elevada resistência periférica, favorecendo complicações como a aterosclerose. Esta disfunção endotelial é parte de um estado pró-trombótico, levando à ocorrência de eventos cardiovasculares, principal causa de morte nestas patologias. O óxido nítrico (NO) tem um papel importante na modulação da atividade plaquetária. Anormalidades na síntese e/ou inativação do NO são descritas tanto na insuficiência renal crônica como na hipertensão. Estudos prévios demonstraram uma redução do influxo de L-arginina em eritrócitos e plaquetas de pacientes hipertensos e em um modelo animal de hipertensão. Além disso, em IRC, nosso grupo mostrou uma ativação da via L-arginina-NO em plaquetas. O objetivo dessa tese é avaliar a via L-arginina-NO na HAS e em diferentes estágios da IRC, bem como investigar o ciclo da uréia, e a presença de marcadores de estresse nesses pacientes. De acordo com o presente estudo pôde-se verificar que não houve alteração na síntese de NO em eritrócitos na hipertensão, todavia ocorre uma ativação do ciclo da uréia, que pode ser dada pelo aumento do influxo de L-arginina eritrocitário previamente demonstrado. Não foi demonstrada diferença significativa na peroxidação lipídica sistêmica, em plaquetas ou eritrócitos na HAS. Em plaquetas, no entanto, houve uma redução da atividade da NO sintase (NOS), que não foi acompanhada por alteração da expressão das isoformas da NOS, da arginase, da fosfodiesterase 5 (PDE5) ou da guanilato ciclase (GC) solúvel. Essa redução na síntese de NO em plaquetas pode ser explicada por um menor influxo de L-arginina que está presente na hipertensão. Os eritrócitos de pacientes renais crônicos em hemodiálise mostraram um maior influxo de L-arginina associado a um aumento da expressão e da atividade da arginase, não havendo diferença na atividade da NOS. Além disso, apesar e não ter sido mostrado alteração nos marcadores de peroxidação lipídica em eritrócitos e plaquetas, foi detectado um aumento dos mesmos no soro de pacientes com IRC em hemodiálise. Por outro lado, as plaquetas dos mesmos pacientes apresentaram uma maior expressão da eNOS, da iNOS e da GC solúvel, acompanhada de uma redução da atividade da arginase, o que pode justificar a disfunção plaquetária que existe nesses pacientes. Plaquetas de pacientes portadores de IRC em tratamento conservador mostraram um aumento da atividade da NOS associado com maior expressão tanto da iNOS como da eNOS. Curiosamente foram detectados menores concentrações de 35-monofosfato de guanosina cíclica (GMPc), não havendo no entanto, diferença nos padrões de agregação plaquetária induzida por colágeno ou adenosina difosfato (ADP). As descobertas aqui apresentadas certamente contribuirão para uma melhor compreensão da fisiopatologia da HAS e da IRC. / Chronic renal failure (CRF) and essential hypertension (EH) are diseases associated with high rates of morbidity and mortality, consuming huge amounts of money from the public health system. The endothelial dysfunction existent in both diseases, CRF and EH, contributes to the maintenance of the high peripheral resistance, and contribute to circulatory complications such as atherosclerosis. This endothelial dysfunction is part of a pro-thrombotic state, leading to cardiovascular events, which are the major cause of death in these disorders. Nitric oxide (NO) plays an important role in the modulation of platelet function. Abnormalities of NO synthesis or inactivation are described in CRF and EH. It was previously reported an inhibition of L-arginine transport in erythrocytes of hypertensive patients and in an animal model of hypertension. Moreover, we have also demonstrated an activation of L-arginine-NO pathway in platelets taken from uraemic patients. The aim of the present thesis is to investigate L-arginine-NO pathway in arterial hypertension and in different stages of chronic renal failure. It will also be evaluated urea cycle and the presence of oxidative stress markers in these patients. According to the present study it was not detected any alteration in erythrocytres NO synthesis in hypertension, however, there was an activation of urea cycle, which could be explained by an increase in L-arginine influx. The present study has not demonstrated significative difference in markers of lipid peroxidation in the serum, platelets or erythrocytes in hypertension. In platelets however, there was an inhibition of NO synthase (NOS) activity without any alterations of NOS isoforms, arginase, phosphodiesterase 5 (PDE5) or soluble guanylyl cyclase (sGC) expression. This reduction of NO synthesis may be explained by a lower influx of L-arginine that is present on hypertension. Erythrocytes from chronic renal failure patients under haemodyalysis have shown an increased influx of L-arginine associated with a higher expression and activity of arginase with no difference in NOS activity. Therefore, although it was not shown abnormalities of lipid per oxidation markers in erythrocytes and platelets, it was detected increased levels of these markers in the serum of chronic renal failure patients under hemodyalysis. On the other hand, platelets from the same patients exhibited increased expression of eNOS, iNOS and soluble guanylyl cyclase associated with reduced arginase activity, which can explain the platelet dysfunction observed in these patients. Platelets taken from patients with chronic renal failure under conservative treatment have shown increased NOS activity associated with higher expression of both iNOS and eNOS. Curiously, it was been detected a lower concentration of cyclic guanosine monophosphate (cGMP), although there was no difference in the patterns of platelet aggregation induced by collagen or adenosine diphosphate (ADP). The findings reported in this study may contribute to a better understanding of EH and CRF physiopathology.

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / A insuficiência renal crônica (IRC) e a hipertensão arterial sistêmica (HAS) são patologias com alta morbidade e mortalidade, consumindo grandes verbas de saúde pública. A disfunção endotelial presente tanto na IRC, como na hipertensão, contribui para a manutenção de elevada resistência periférica, favorecendo complicações como a aterosclerose. Esta disfunção endotelial é parte de um estado pró-trombótico, levando à ocorrência de eventos cardiovasculares, principal causa de morte nestas patologias. O óxido nítrico (NO) tem um papel importante na modulação da atividade plaquetária. Anormalidades na síntese e/ou inativação do NO são descritas tanto na insuficiência renal crônica como na hipertensão. Estudos prévios demonstraram uma redução do influxo de L-arginina em eritrócitos e plaquetas de pacientes hipertensos e em um modelo animal de hipertensão. Além disso, em IRC, nosso grupo mostrou uma ativação da via L-arginina-NO em plaquetas. O objetivo dessa tese é avaliar a via L-arginina-NO na HAS e em diferentes estágios da IRC, bem como investigar o ciclo da uréia, e a presença de marcadores de estresse nesses pacientes. De acordo com o presente estudo pôde-se verificar que não houve alteração na síntese de NO em eritrócitos na hipertensão, todavia ocorre uma ativação do ciclo da uréia, que pode ser dada pelo aumento do influxo de L-arginina eritrocitário previamente demonstrado. Não foi demonstrada diferença significativa na peroxidação lipídica sistêmica, em plaquetas ou eritrócitos na HAS. Em plaquetas, no entanto, houve uma redução da atividade da NO sintase (NOS), que não foi acompanhada por alteração da expressão das isoformas da NOS, da arginase, da fosfodiesterase 5 (PDE5) ou da guanilato ciclase (GC) solúvel. Essa redução na síntese de NO em plaquetas pode ser explicada por um menor influxo de L-arginina que está presente na hipertensão. Os eritrócitos de pacientes renais crônicos em hemodiálise mostraram um maior influxo de L-arginina associado a um aumento da expressão e da atividade da arginase, não havendo diferença na atividade da NOS. Além disso, apesar e não ter sido mostrado alteração nos marcadores de peroxidação lipídica em eritrócitos e plaquetas, foi detectado um aumento dos mesmos no soro de pacientes com IRC em hemodiálise. Por outro lado, as plaquetas dos mesmos pacientes apresentaram uma maior expressão da eNOS, da iNOS e da GC solúvel, acompanhada de uma redução da atividade da arginase, o que pode justificar a disfunção plaquetária que existe nesses pacientes. Plaquetas de pacientes portadores de IRC em tratamento conservador mostraram um aumento da atividade da NOS associado com maior expressão tanto da iNOS como da eNOS. Curiosamente foram detectados menores concentrações de 35-monofosfato de guanosina cíclica (GMPc), não havendo no entanto, diferença nos padrões de agregação plaquetária induzida por colágeno ou adenosina difosfato (ADP). As descobertas aqui apresentadas certamente contribuirão para uma melhor compreensão da fisiopatologia da HAS e da IRC. / Chronic renal failure (CRF) and essential hypertension (EH) are diseases associated with high rates of morbidity and mortality, consuming huge amounts of money from the public health system. The endothelial dysfunction existent in both diseases, CRF and EH, contributes to the maintenance of the high peripheral resistance, and contribute to circulatory complications such as atherosclerosis. This endothelial dysfunction is part of a pro-thrombotic state, leading to cardiovascular events, which are the major cause of death in these disorders. Nitric oxide (NO) plays an important role in the modulation of platelet function. Abnormalities of NO synthesis or inactivation are described in CRF and EH. It was previously reported an inhibition of L-arginine transport in erythrocytes of hypertensive patients and in an animal model of hypertension. Moreover, we have also demonstrated an activation of L-arginine-NO pathway in platelets taken from uraemic patients. The aim of the present thesis is to investigate L-arginine-NO pathway in arterial hypertension and in different stages of chronic renal failure. It will also be evaluated urea cycle and the presence of oxidative stress markers in these patients. According to the present study it was not detected any alteration in erythrocytres NO synthesis in hypertension, however, there was an activation of urea cycle, which could be explained by an increase in L-arginine influx. The present study has not demonstrated significative difference in markers of lipid peroxidation in the serum, platelets or erythrocytes in hypertension. In platelets however, there was an inhibition of NO synthase (NOS) activity without any alterations of NOS isoforms, arginase, phosphodiesterase 5 (PDE5) or soluble guanylyl cyclase (sGC) expression. This reduction of NO synthesis may be explained by a lower influx of L-arginine that is present on hypertension. Erythrocytes from chronic renal failure patients under haemodyalysis have shown an increased influx of L-arginine associated with a higher expression and activity of arginase with no difference in NOS activity. Therefore, although it was not shown abnormalities of lipid per oxidation markers in erythrocytes and platelets, it was detected increased levels of these markers in the serum of chronic renal failure patients under hemodyalysis. On the other hand, platelets from the same patients exhibited increased expression of eNOS, iNOS and soluble guanylyl cyclase associated with reduced arginase activity, which can explain the platelet dysfunction observed in these patients. Platelets taken from patients with chronic renal failure under conservative treatment have shown increased NOS activity associated with higher expression of both iNOS and eNOS. Curiously, it was been detected a lower concentration of cyclic guanosine monophosphate (cGMP), although there was no difference in the patterns of platelet aggregation induced by collagen or adenosine diphosphate (ADP). The findings reported in this study may contribute to a better understanding of EH and CRF physiopathology.

L’analyse spectrale de la fréquence cardiaque, de la pression artérielle systolique, de la pression artérielle diastolique ainsi que de la respiration par la transformée de Fourier rapide, est considérée comme une technique non invasive pour la détermination de l’activité du système nerveux autonome (SNA). Dans une population de sujets normaux volontaires, nous avons obtenu à l’état basal, des oscillations de basses fréquences (0,05-0,15Hz) reliées au système nerveux sympathique autonome et des oscillations de hautes fréquences (0,2Hz) représentant sur les intervalles entre chaque ondes R de l’électrocardiogramme (RR), l’arythmie sinusale respiratoire correspondant à une activité vagale. Nous avons comparé les tests de stimulation du système nerveux sympathique autonome déclenché par le passage de la position de repos (en décubitus dorsal), à la position orthostatique volontaire et le passage de la position de repos à la position orthostatique avec la table basculante à 60o. Nous avons également comparé un groupe normotendu à un groupe hypertendu qui a été soumis au passage du repos à l’orthostation volontaire et pour lesquels nous avons évalué la sensibilité du baroréflexe et la réponse sympathique par la mesure des catécholamines circulantes. Dans un groupe de sujets ayant une hypertension artérielle essentielle, nous avons évalué l’effet de la thérapie hypotensive, par le Trandolapril qui est un Inhibiteur de l’enzyme de conversion (IEC) de l`angiotensine. Dans ce groupe hypertendu, nous avons procédé, en plus de la stimulation sympathique par l’orthostation volontaire, à un exercice isométrique de trois minutes à 30 % de la force maximale. Nous avons également complété notre évaluation par la mesure de la densité de récepteurs ß2 adrénergiques sur lymphocytes et par la mesure des indices de contractilité à l’aide de l’échocardiographie en M mode. Les résultats ont montré, dans les groupes normaux volontaires, dans les deux types de stimulation du système nerveux sympathique par la position orthostatique, une augmentation significative des catécholamines plasmatiques avec une augmentation de la fréquence cardiaque et des basses fréquences de RR, confirmant ainsi que l’on est en état de stimulation sympathique. On observe en même temps une diminution significative des hautes fréquences de RR, suggérant un retrait vagal lors de cette stimulation. On a observé au test de la table basculante six cas d’hypotension orthostatique. On a comparé la position orthostatique volontaire entre le groupe de sujets normaux et le groupe de sujets hypertendus. L’analyse spectrale croisée de RR et de la pression artérielle systolique a permis d’évaluer dans l’hypertension artérielle (HTA), essentielle une sensibilité du baroréflexe atténuée, accompagnée d’une réactivité vagale réduite en présence d’une activité et d’une réactivité sympathique augmentées suggérant une altération sympathovagale dans l’HTA. Dans le groupe de sujets hypertendus traités (Trandolapril 2mg/jour), nous avons identifié un groupe de répondeurs au traitement par le Trandolapril et un groupe de non répondeurs à ce type de thérapie anti-hypertensive. Le groupe répondeur avait un profil hyper-adrénergique avec une hyper-réactivité sympathique, une fréquence cardiaque et des pressions artérielles diastolique et systolique plus élevées au repos. Dans le groupe total traité au Trandolapril, la densité des récepteurs ß2 adrénergiques a doublé, après thérapie, alors que la réactivité des basses fréquences obtenues à l’analyse spectrale a augmenté. Nous avons montré dans notre étude qu’un IECA a pu inhiber le mécanisme facilitateur de l’angII sur les terminaisons nerveuses sympathiques et a permis ainsi de réduire l’hyperactivité sympathique et le mécanisme de « down regulation » des récepteurs ß2 adrénergiques rendant ainsi l’expression de l’influence du SNA post synaptique plus efficace. Dans l’ensemble de nos protocoles cliniques, par l’utilisation de l’analyse spectrale des signaux RR, de la pression artérielle systolique,de la pression artérielle diastolique et de la respiration, nous avons montré que cette technique non invasive permet de décrire et de mieux comprendre les mécanismes physiologiques, physiopathologiques et pharmacologiques reliés au système nerveux autonome et à l’hypertension artérielle essentielle. / The spectral analysis of the heart rate, the systolic blood pressure, the diastolic blood pressure and the respiration with the Fast Fourier Transform, is considered as a non-invasive technique for the determination of the autonomic nervous system activity. In a population of normal volunteer subjects, we obtained in the basal state, low-frequency oscillations related to the sympathetic autonomous nervous system (0.05-0.15Hz) and the high-frequency oscillations (0.2Hz), which represent, on RR intervals, the respiratory sinus arrhythmia corresponding to vagal activity. We compared the sympathetic nervous system stimulation tests triggered by the transition from resting to voluntary orthostatic positions and the transition from resting to orthostatic position using tilt table at 60o. We also compared a normal blood pressure group to a hypertensive group which were both subject to the transition from resting to voluntary orthostation and for whom we evaluated the baroreflex sensitivity and the sympathetic response by measuring circulating catecholamines. In a group of subjects having an essential arterial hypertension, we have evaluated the effect of hypotensive therapy, by the Trandolapril which is an Angiotensin Converting Enzyme Inhibitor. In the hypertensive group, we evaluated the sympathetic stimulation using the voluntary orthostation, and we have also proceeded to a 3 minutes isometric exercise at 30% of maximum force. We have also completed our evaluation by measuring both the ß2 adrenergic receptor density on isolated lymphocytes and the contractility index using the echocardiography in M mode. In both sympathetic nervous system stimulation types by orthostatic position, the results have shown, for normal blood pressure volunteer subject groups, a significant increase in concentration of plasma catecholamines with an increase of heart rate (HR) and the low frequency RR, confirming therefore that we are in the presence of a sympathetic stimulation state. At the same time, we observed a significant decrease of high frequency of RR, suggesting a vagal withdrawal during the stimulation. We observed six cases of orthostatic hypotension from the tilt table test. We compared the voluntary orthostatic position between normal and hypertension subject groups. The results with combined spectral analysis of RR and the systolic blood pressure allowed to evaluate in the essential high blood pressure a reduced baroreflex sensitivity along with a reduced vagal reactivity in presence of increased sympathetic activity and reactivity suggesting a sympatho-vagal alteration in essential arterial hypertension. In hypertensive subjects treated with Trandolapril 2mg/day, we have identified a group responding to Trandolapril treatment and a group of non-responders to this type of anti-hypertensive therapy. The responding group has an hyper-adrenergic profile with higher sympathetic reactivity, heart rate and arterial diastolic and systolic pressures at rest. In the total group treated with Trandolapril, the ß2 adrenergic receptor density has doubled after therapy, while the reactivity of low frequencies obtained from spectral analysis has increased. We have shown in this study that Angiotensin Converting Enzyme Inhibitor could inhibit the facilitatory mechanism of angII on sympathetic nerve terminals and therefore allowed the reduction of the sympathetic hyperactivity and the cause of a beta2 adrenergic “down regulation”. Thus it allowed us to obtain an increased density of the receptors and the expression of more effective influence of post synaptic Sympathetic nervous system. In all of our clinical protocols, using spectral analysis of RR, systolic blood pressure, diastolic blood pressure and breathing signals, we have shown that this non-invasive technique has helped to describe and to better understand the physiological and pharmacological mechanisms related to the autonomic nervous system in normotensive and hypertensive subjects.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

L’analyse spectrale de la fréquence cardiaque, de la pression artérielle systolique, de la pression artérielle diastolique ainsi que de la respiration par la transformée de Fourier rapide, est considérée comme une technique non invasive pour la détermination de l’activité du système nerveux autonome (SNA). Dans une population de sujets normaux volontaires, nous avons obtenu à l’état basal, des oscillations de basses fréquences (0,05-0,15Hz) reliées au système nerveux sympathique autonome et des oscillations de hautes fréquences (0,2Hz) représentant sur les intervalles entre chaque ondes R de l’électrocardiogramme (RR), l’arythmie sinusale respiratoire correspondant à une activité vagale. Nous avons comparé les tests de stimulation du système nerveux sympathique autonome déclenché par le passage de la position de repos (en décubitus dorsal), à la position orthostatique volontaire et le passage de la position de repos à la position orthostatique avec la table basculante à 60o. Nous avons également comparé un groupe normotendu à un groupe hypertendu qui a été soumis au passage du repos à l’orthostation volontaire et pour lesquels nous avons évalué la sensibilité du baroréflexe et la réponse sympathique par la mesure des catécholamines circulantes. Dans un groupe de sujets ayant une hypertension artérielle essentielle, nous avons évalué l’effet de la thérapie hypotensive, par le Trandolapril qui est un Inhibiteur de l’enzyme de conversion (IEC) de l`angiotensine. Dans ce groupe hypertendu, nous avons procédé, en plus de la stimulation sympathique par l’orthostation volontaire, à un exercice isométrique de trois minutes à 30 % de la force maximale. Nous avons également complété notre évaluation par la mesure de la densité de récepteurs ß2 adrénergiques sur lymphocytes et par la mesure des indices de contractilité à l’aide de l’échocardiographie en M mode. Les résultats ont montré, dans les groupes normaux volontaires, dans les deux types de stimulation du système nerveux sympathique par la position orthostatique, une augmentation significative des catécholamines plasmatiques avec une augmentation de la fréquence cardiaque et des basses fréquences de RR, confirmant ainsi que l’on est en état de stimulation sympathique. On observe en même temps une diminution significative des hautes fréquences de RR, suggérant un retrait vagal lors de cette stimulation. On a observé au test de la table basculante six cas d’hypotension orthostatique. On a comparé la position orthostatique volontaire entre le groupe de sujets normaux et le groupe de sujets hypertendus. L’analyse spectrale croisée de RR et de la pression artérielle systolique a permis d’évaluer dans l’hypertension artérielle (HTA), essentielle une sensibilité du baroréflexe atténuée, accompagnée d’une réactivité vagale réduite en présence d’une activité et d’une réactivité sympathique augmentées suggérant une altération sympathovagale dans l’HTA. Dans le groupe de sujets hypertendus traités (Trandolapril 2mg/jour), nous avons identifié un groupe de répondeurs au traitement par le Trandolapril et un groupe de non répondeurs à ce type de thérapie anti-hypertensive. Le groupe répondeur avait un profil hyper-adrénergique avec une hyper-réactivité sympathique, une fréquence cardiaque et des pressions artérielles diastolique et systolique plus élevées au repos. Dans le groupe total traité au Trandolapril, la densité des récepteurs ß2 adrénergiques a doublé, après thérapie, alors que la réactivité des basses fréquences obtenues à l’analyse spectrale a augmenté. Nous avons montré dans notre étude qu’un IECA a pu inhiber le mécanisme facilitateur de l’angII sur les terminaisons nerveuses sympathiques et a permis ainsi de réduire l’hyperactivité sympathique et le mécanisme de « down regulation » des récepteurs ß2 adrénergiques rendant ainsi l’expression de l’influence du SNA post synaptique plus efficace. Dans l’ensemble de nos protocoles cliniques, par l’utilisation de l’analyse spectrale des signaux RR, de la pression artérielle systolique,de la pression artérielle diastolique et de la respiration, nous avons montré que cette technique non invasive permet de décrire et de mieux comprendre les mécanismes physiologiques, physiopathologiques et pharmacologiques reliés au système nerveux autonome et à l’hypertension artérielle essentielle. / The spectral analysis of the heart rate, the systolic blood pressure, the diastolic blood pressure and the respiration with the Fast Fourier Transform, is considered as a non-invasive technique for the determination of the autonomic nervous system activity. In a population of normal volunteer subjects, we obtained in the basal state, low-frequency oscillations related to the sympathetic autonomous nervous system (0.05-0.15Hz) and the high-frequency oscillations (0.2Hz), which represent, on RR intervals, the respiratory sinus arrhythmia corresponding to vagal activity. We compared the sympathetic nervous system stimulation tests triggered by the transition from resting to voluntary orthostatic positions and the transition from resting to orthostatic position using tilt table at 60o. We also compared a normal blood pressure group to a hypertensive group which were both subject to the transition from resting to voluntary orthostation and for whom we evaluated the baroreflex sensitivity and the sympathetic response by measuring circulating catecholamines. In a group of subjects having an essential arterial hypertension, we have evaluated the effect of hypotensive therapy, by the Trandolapril which is an Angiotensin Converting Enzyme Inhibitor. In the hypertensive group, we evaluated the sympathetic stimulation using the voluntary orthostation, and we have also proceeded to a 3 minutes isometric exercise at 30% of maximum force. We have also completed our evaluation by measuring both the ß2 adrenergic receptor density on isolated lymphocytes and the contractility index using the echocardiography in M mode. In both sympathetic nervous system stimulation types by orthostatic position, the results have shown, for normal blood pressure volunteer subject groups, a significant increase in concentration of plasma catecholamines with an increase of heart rate (HR) and the low frequency RR, confirming therefore that we are in the presence of a sympathetic stimulation state. At the same time, we observed a significant decrease of high frequency of RR, suggesting a vagal withdrawal during the stimulation. We observed six cases of orthostatic hypotension from the tilt table test. We compared the voluntary orthostatic position between normal and hypertension subject groups. The results with combined spectral analysis of RR and the systolic blood pressure allowed to evaluate in the essential high blood pressure a reduced baroreflex sensitivity along with a reduced vagal reactivity in presence of increased sympathetic activity and reactivity suggesting a sympatho-vagal alteration in essential arterial hypertension. In hypertensive subjects treated with Trandolapril 2mg/day, we have identified a group responding to Trandolapril treatment and a group of non-responders to this type of anti-hypertensive therapy. The responding group has an hyper-adrenergic profile with higher sympathetic reactivity, heart rate and arterial diastolic and systolic pressures at rest. In the total group treated with Trandolapril, the ß2 adrenergic receptor density has doubled after therapy, while the reactivity of low frequencies obtained from spectral analysis has increased. We have shown in this study that Angiotensin Converting Enzyme Inhibitor could inhibit the facilitatory mechanism of angII on sympathetic nerve terminals and therefore allowed the reduction of the sympathetic hyperactivity and the cause of a beta2 adrenergic “down regulation”. Thus it allowed us to obtain an increased density of the receptors and the expression of more effective influence of post synaptic Sympathetic nervous system. In all of our clinical protocols, using spectral analysis of RR, systolic blood pressure, diastolic blood pressure and breathing signals, we have shown that this non-invasive technique has helped to describe and to better understand the physiological and pharmacological mechanisms related to the autonomic nervous system in normotensive and hypertensive subjects.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal