Thesis (Ph.D.)--Murdoch University, 2008. / Thesis submitted to the Faculty of Health Sciences. Includes bibliographical references (leaves 210-247)

Bibliographische Beschreibung Schreiber, Juliane Untersuchung des Einflusses von Persönlichkeitscharakteristika und Bewältigungsstrategien auf den Blutdruck bei Essentieller Hypertonie Universität Leipzig, Dissertation 85 S.1, 85 Lit.2, 30 Abb., 7 Tab., 11 Anlagen Referat: Bluthochdruck nimmt aufgrund seiner weiten Verbreitung in der Bevölkerung und den schweren Folgeerkrankungen einen großen Stellenwert in Forschung und Klinik ein. Die Ursache für die Entstehung der häufigsten Form des Bluthochdrucks, der Essentiellen Arteriellen Hypertonie, ist bis heute unzureichend geklärt. Es gibt Erklärungsansätze, dass Hypertonie mit bestimmten Persönlichkeitsmerkmalen einhergeht. Andererseits existieren auch Beobachtungen, welche den Schluss zulassen, dass einige Charakterzüge als Risikofaktoren fungieren könnten. Ziel der vorliegenden Pilotstudie war es, einen Beitrag zur Rolle von Persönlichkeitsmerkmalen und Bewältigungsstrategien bei der Entstehung einer Essentiellen Hypertonie zu leisten. Die vorliegende Arbeit ist Teil einer übergeordneten Studie, die hierzu einen umfassenden Beitrag unter Einschluss von Genetik und Bildgebung des Gehirns leisten sollte. Es erfolgte die Diagnosesicherung einer Essentiellen Hypertonie basierend auf einer systematischen mehrmaligen Blutdruckmessung, verschiedenen Laborparametern zum Ausschluss anderer möglicher Ursachen einer arteriellen Hypertonie und einer eingehenden Anamnese. Als Hauptzielgrößen sollten neben den mittleren Blutdruckwerten vor allem Daten zu Depression, Lebenseinstellung, Ängstlichkeit, Umgang mit Ärger und Stress mittels einer Batterie von Fragebögen gewonnen werden. Hinzu kam die Erforschung der Persönlichkeitsdimensionen Neurotizismus, Extraversion, Offenheit für Erfahrungen, Verträglichkeit und Gewissenhaftigkeit. Anhand der Daten wurden die Teilnehmer in zwei Gruppen eingeteilt: Probanden mit (1) Essentieller Hypertonie sowie solche mit (2) normotonen Blutruckwerten. Bezüglich Geschlecht, Blutdruckwerten etc. erwies sich das Studienkollektiv im Hinblick auf die Bevölkerung als repräsentativ. Mit Hilfe dieser Daten konnten Gruppenvergleiche gezogen werden, des Weiteren wurden parametrische Korrelationen über die Gesamtgruppe der Probanden über mögliche Zusammenhänge zwischen verschiedenen Persönlichkeitsmerkmalen und systolischen bzw. diastolischen Blutdruckwerten durchgeführt. Die Auswertung der Hauptzielgrößen spricht dafür, dass bestimmte Persönlichkeitsfaktoren mit dem Merkmal „Essentielle Hypertonie“ assoziiert zu sein scheinen. Die vorliegenden Befunde stützen somit die Hypothese eines Zusammenhanges von Persönlichkeit und der Entwicklung einer Essentiellen Hypertonie, sollten jedoch auf Grund der geringen Stichprobengröße (n=49) vorsichtig interpretiert werden. ____________________ 1 Seitenzahl insgesamt 2 Zahl der im Literaturverzeichnis ausgewiesenen Literaturangaben

Background: Essential hypertension is regarded as a complex disease, the phenotype of which results from interactions between numerous genes and environmental factors. Genome-wide association studies of blood pressure (BP) and hypertension have been developed to explore the potential genes involved in blood pressure and identified a number of trait-associated variants. Among those variants, single nucleotide polymorphisms (SNPs) rs1173771 (G/A) and rs1421811 (G/C) are located at the natriuretic peptide receptor C (NPR3) gene locus. Their major alleles are related with blood pressure elevation. Studies have implicated NPR-C in mediating some of the cardio-protective actions of natriuretic peptides and its direct involvement in the pathogenesis of hypertension. However, the precise role of these association between genetic variants at NPR3 and blood pressure control has not been elucidated. Objective: To functionally characterise the effect of BP-associated SNPs at the NPR3 gene locus in the context of BP regulatory pathways. Methods: Primary human umbilical artery smooth muscle (HUASMCs) and vein endothelial (HUVECs) cells were genotyped for BP-associated NPR3 variants. Endogenous mRNA and protein expression levels were assessed by qRT-PCR, allelic expression imbalance assay and western blotting. Open chromatin regions were assayed using formaldehyde-assisted isolation of regulatory elements (FAIRE). Interaction between variants flanking region with nuclear protein was detected by electrophoretic mobility shift assay (EMSA). Cell proliferation and migration were 4 determined by cell counting and scratch assays. Angiotensin II (Ang II)-induced calcium flux was evaluated using the intracellular fluorescent probe. Results: The BP-elevating allele of the NPR3 variants in rs1173771 linkage disequilibrium (LD) block was associated with lower endogenous mRNA and protein levels in HUASMCs. This is consistent with the finding that BP-elevating allele is less located within open chromatin. The decreased NPR3 expression in HUASMCs carrying the BP-elevating allele is associated with increased cell proliferation and intracellular calcium flux in response to Ang II stimulation. No differences in migration rates were detected. No genotype-dependent characteristics were observed in HUVECs NPR3 expression and cell proliferation. Moreover, RT-PCR showed a linkage between of the BP-elevating allele of the NPR3 variants in rs1421811 LD block and lower endogenous mRNA in HUASMCs. Intracellular calcium flux detection also revealed a trend of higher response to Ang II stimulation in BP-elevating allele homozygous HUASMCs. However, No genetic differences were detected in proliferation and migration rates of HUASMCs, and HUVECs NPR3 expression and cell proliferation studies did not present any significant genotype-dependent association. Conclusions: This study has identified a potential mechanism for BP-associated SNPs at NPR3 locus to influence BP predominantly via an effect on vascular smooth muscle cell behaviours.

M.Tech. (Homoeopathy) / Hypertension is one of the major cardiovascular diseases worldwide. It is a major cause of morbidity and mortality and this is mainly caused by heart and renal diseases (Alhalaiqa et al., 2011). Hypertension is common in South Africa. About a quarter of all South Africans, 15 years and older, suffer from hypertension (Steyn, 1998). There are 6.1 million people with a blood pressure equal to or above 140/90 mmHg, 23% of South African men are hypertensive and for women the equivalent prevalence is 16% (South African Demographic and Health Survey, 1998). Allopathic anti-hypertensive drugs are not always effective or well tolerated due to their many harmful side effects (Ahmad, 1999). Homoeopathy though, does not have unwanted side effects (Digby, 1997). The aim of this study is to ascertain the efficacy of a homoeopathic complex containing Crataegus oxycantha 6CH, Viscum album 6CH, Glonoine 6CH and Digitalis purpurea 6CH in treating essential hypertension in black adults between the ages of eighteen and fifty five years. The study was a randomised double-blind placebo controlled study and thirty male and female participants were recruited and divided into the treatment and the placebo group. Three participants withdrew from the study during the trial period and therefore twenty seven participants were in this study. The treatment group was administered the homoeopathic complex remedy and the placebo group was administered the placebo. Participants received medication which they took for six weeks according to proper instructions. They were requested not to make any substantial changes to their lifestyle and diet. The blood pressure readings were monitored every two weeks for the six weeks duration of the study. Collected data was analysed using the analysis of variance (ANOVA) test to determine the statistical significance of changes in the mean systolic and diastolic blood pressure and in the symptoms that the participants had during the study. The analysis compared the variables between and within the two groups. The inter-group statistical analysis was done using the Mann-Whitney Test. The intra-group statistical analysis was done using the non-parametric test (Friedman Test). The difference between the two groups over time was done using the Post-Hoc Test. The Post-Hoc test analysis with Wilcoxon The homoeopathic remedy complex provided a statistically significant decrease in systolic blood pressure readings compared to the placebo. The diastolic blood pressure of the treatment group also decreased, and that of the placebo group decreased gradually. In the treatment group the most significant symptomatic relief was from headaches and vertigo. The other symptoms slightly decreased in the second week and then remained constant. In the placebo group there was a slight relief of the headache and vertigo symptoms but it was not significant. The homoeopathic complex remedy provided a statistically significant decrease in systolic blood pressure readings. This provides a safe and effective alternative treatment for essential hypertension.

No description available.

Introdução A baixa concentração sérica de vitamina D tem sido associadas com a hipertensão no mundo todo. A hipovitaminose D tem sido observada mesmo na nossa população. Objetivo Investigar as concentrações séricas de vitamina D e sua associação com a pressão arterial (PA) em indivíduos adultos residentes na cidade de São Paulo. Métodos Para esta dissertação foram desenvolvidos dois artigos. Na revisão (artigo 1), foram selecionados artigos indexados nas bases de dados Pubmed, Lilacs e Medline, incluindo estudos realizados no Brasil. O artigo original (artigo 2) descreve o estudo transversal realizado com 332 adultos, 65 por cento mulheres, onde foi avaliada a associação entre vitamina D, paratormônio intacto (PTHi) e PA. Foram feitas: aferição da PA e coleta de medidas antropométricas e amostras sanguíneas. A concentração sérica de 25(OH)D3 foi mensurada pela técnica de cromatografia líquida de alta eficiência (HPLC). O valor médio de 2 medidas de PA foi considerado para as análises. Os participantes foram divididos em 3 grupos: (1) PA normal; (2) PA elevada; (3) PA normal pelo uso de medicação. A insuficiência de vitamina D foi considerada quando 25(OH)D3 75 nmol/L e o PTHi elevado quando > 65 pg/mL. A relação entre vitamina D, PTHi e PA foi ajustada pelo índice de massa corpórea (IMC), circunferência da cintura (CC) e perfil lipídico. Resultados Na revisão foi enfatizada a relação da vitamina D com doenças cardiovasculares, considerando, inclusive, os diferentes mecanismos fisiológicos propostos. No artigo original, observou-se idade média e desvio padrão de 50 (15) anos, IMC 29 (6) kg/m² e CC 97 (13) cm. Entre os indivíduos avaliados, 75 por cento tinham sobrepeso ou obesidade. PA média foi 129/80 (18/11) mmHg. A concentração média de cálcio sérico foi 9,3 (0,5) mg/dL, PTHi 40,8 (18,7) pg/mL e vitamina D 55,8 (17,1) nmol/L. O PTHi elevado e a insuficiência de vitamina D estiveram presentes em 12 por cento e 86 por cento da amostra, respectivamente. Não foram observadas diferenças nas prevalências de insuficiência de vitamina D e PTHi elevado entre os grupos de PA. Não foram observadas associações entre vitamina D e PA. Entretanto, uma correlação positiva foi observada entre PTHi e PA sistólica (r=0,168; p=0,002) e diastólica (r=0,168; p=0,002), IMC (r=0,125; p=0,023), CC (r=0,172; p=0,002) e por cento de massa gorda (r=0,158; p=0,004). O PTHi manteve-se correlacionado com a PA mesmo após realização dos ajustes. Conclusão A associação entre PTH e pressão arterial, observada por este estudo, acrescenta novas informações com relação ao envolvimento do metabolismo da vitamina D na regulação da pressão arterial. Mais estudos são necessários para esclarecer as vias metabólicas existentes entre metabolismo do PTH, da vitamina D e da pressão arterial / Background Low vitamin D has been associated with hypertension worldwide. Hypovitaminosis D has also been observed in our population. Objective To evaluate whether vitamin D status are related to blood pressure (BP) in adults living at Sao Paulo city. Methods For this dissertation, two articles were developed. In review (article 1), articles indexed in database Pubmed, Lilacs and Medline were selected, including Brazilian studies. Original article (article 2) describe cross-sectional study performed with 332 adults, 65 per cent women, that evaluate the association between vitamin D, intact parathyroid hormone (iPTH) and BP. Anthropometric measurements, BP and a fasting blood sample were obtained. Serum concentration of 25(OH)D3 was measured by highperformance liquid chromatography (HPLC) technique. Mean value of two measures of BP was considered to analysis. Participants were divided in three categories of blood pressure: (1) normal blood pressure; (2) high blood pressure; (3) normal blood pressure by medication. Vitamin D insufficiency was defined by 25(OH)D3 75 nmol/L, high iPTH > 65 pg/mL. The relationship between vitamin D, iPTH and BP were adjusted for body mass index (BMI), waist circumference (WC), blood lipids. Results In review, the relationship of vitamin D with cardiovascular disease was emphasized considering the different physiological mechanisms proposed. In the original article, mean age and standard deviation was 50 (15) years, BMI 29 (6) kg/m², WC 97 (13) cm. Overweight and obesity was present in 75 per cent of individuals. Mean BP was 129/80 (18/11) mmHg. Mean serum calcium concentration was 9.3 (0.5) mg/dL, iPTH 40.8(18.7) pg/mL and vitamin D 55.8 (17.1) nmol/L. Elevated iPTH and vitamin D insufficiency was present in 12 per cent and 86 per cent of the sample, respectively. No differences were observed on prevalence of vitamin D insufficiency and high iPTH among blood pressure groups. No significant association was observed between BP and vitamin D. However, a positive correlation was observed between iPTH and systolic (r=0.168; p=0.002) and diastolic BP (r=0.168; p=0.002), BMI (r=0.125; p=0.023), WC (r=0.172; p=0.002) and per cent FM (r=0.158; p=0.004). The iPTH remained correlated with BP even with adjustments. Conclusion The association between PTH and blood pressure observed in this study adds a new piece of information in literature regarding the involvement of the vitamin D metabolism with blood pressure. More studies are necessary to clarifying the metabolic pathways existing between PTH, vitamin D and blood pressure

Introdução A baixa concentração sérica de vitamina D tem sido associadas com a hipertensão no mundo todo. A hipovitaminose D tem sido observada mesmo na nossa população. Objetivo Investigar as concentrações séricas de vitamina D e sua associação com a pressão arterial (PA) em indivíduos adultos residentes na cidade de São Paulo. Métodos Para esta dissertação foram desenvolvidos dois artigos. Na revisão (artigo 1), foram selecionados artigos indexados nas bases de dados Pubmed, Lilacs e Medline, incluindo estudos realizados no Brasil. O artigo original (artigo 2) descreve o estudo transversal realizado com 332 adultos, 65 por cento mulheres, onde foi avaliada a associação entre vitamina D, paratormônio intacto (PTHi) e PA. Foram feitas: aferição da PA e coleta de medidas antropométricas e amostras sanguíneas. A concentração sérica de 25(OH)D3 foi mensurada pela técnica de cromatografia líquida de alta eficiência (HPLC). O valor médio de 2 medidas de PA foi considerado para as análises. Os participantes foram divididos em 3 grupos: (1) PA normal; (2) PA elevada; (3) PA normal pelo uso de medicação. A insuficiência de vitamina D foi considerada quando 25(OH)D3 75 nmol/L e o PTHi elevado quando > 65 pg/mL. A relação entre vitamina D, PTHi e PA foi ajustada pelo índice de massa corpórea (IMC), circunferência da cintura (CC) e perfil lipídico. Resultados Na revisão foi enfatizada a relação da vitamina D com doenças cardiovasculares, considerando, inclusive, os diferentes mecanismos fisiológicos propostos. No artigo original, observou-se idade média e desvio padrão de 50 (15) anos, IMC 29 (6) kg/m² e CC 97 (13) cm. Entre os indivíduos avaliados, 75 por cento tinham sobrepeso ou obesidade. PA média foi 129/80 (18/11) mmHg. A concentração média de cálcio sérico foi 9,3 (0,5) mg/dL, PTHi 40,8 (18,7) pg/mL e vitamina D 55,8 (17,1) nmol/L. O PTHi elevado e a insuficiência de vitamina D estiveram presentes em 12 por cento e 86 por cento da amostra, respectivamente. Não foram observadas diferenças nas prevalências de insuficiência de vitamina D e PTHi elevado entre os grupos de PA. Não foram observadas associações entre vitamina D e PA. Entretanto, uma correlação positiva foi observada entre PTHi e PA sistólica (r=0,168; p=0,002) e diastólica (r=0,168; p=0,002), IMC (r=0,125; p=0,023), CC (r=0,172; p=0,002) e por cento de massa gorda (r=0,158; p=0,004). O PTHi manteve-se correlacionado com a PA mesmo após realização dos ajustes. Conclusão A associação entre PTH e pressão arterial, observada por este estudo, acrescenta novas informações com relação ao envolvimento do metabolismo da vitamina D na regulação da pressão arterial. Mais estudos são necessários para esclarecer as vias metabólicas existentes entre metabolismo do PTH, da vitamina D e da pressão arterial / Background Low vitamin D has been associated with hypertension worldwide. Hypovitaminosis D has also been observed in our population. Objective To evaluate whether vitamin D status are related to blood pressure (BP) in adults living at Sao Paulo city. Methods For this dissertation, two articles were developed. In review (article 1), articles indexed in database Pubmed, Lilacs and Medline were selected, including Brazilian studies. Original article (article 2) describe cross-sectional study performed with 332 adults, 65 per cent women, that evaluate the association between vitamin D, intact parathyroid hormone (iPTH) and BP. Anthropometric measurements, BP and a fasting blood sample were obtained. Serum concentration of 25(OH)D3 was measured by highperformance liquid chromatography (HPLC) technique. Mean value of two measures of BP was considered to analysis. Participants were divided in three categories of blood pressure: (1) normal blood pressure; (2) high blood pressure; (3) normal blood pressure by medication. Vitamin D insufficiency was defined by 25(OH)D3 75 nmol/L, high iPTH > 65 pg/mL. The relationship between vitamin D, iPTH and BP were adjusted for body mass index (BMI), waist circumference (WC), blood lipids. Results In review, the relationship of vitamin D with cardiovascular disease was emphasized considering the different physiological mechanisms proposed. In the original article, mean age and standard deviation was 50 (15) years, BMI 29 (6) kg/m², WC 97 (13) cm. Overweight and obesity was present in 75 per cent of individuals. Mean BP was 129/80 (18/11) mmHg. Mean serum calcium concentration was 9.3 (0.5) mg/dL, iPTH 40.8(18.7) pg/mL and vitamin D 55.8 (17.1) nmol/L. Elevated iPTH and vitamin D insufficiency was present in 12 per cent and 86 per cent of the sample, respectively. No differences were observed on prevalence of vitamin D insufficiency and high iPTH among blood pressure groups. No significant association was observed between BP and vitamin D. However, a positive correlation was observed between iPTH and systolic (r=0.168; p=0.002) and diastolic BP (r=0.168; p=0.002), BMI (r=0.125; p=0.023), WC (r=0.172; p=0.002) and per cent FM (r=0.158; p=0.004). The iPTH remained correlated with BP even with adjustments. Conclusion The association between PTH and blood pressure observed in this study adds a new piece of information in literature regarding the involvement of the vitamin D metabolism with blood pressure. More studies are necessary to clarifying the metabolic pathways existing between PTH, vitamin D and blood pressure

Bibliographische Beschreibung Schreiber, Juliane Untersuchung des Einflusses von Persönlichkeitscharakteristika und Bewältigungsstrategien auf den Blutdruck bei Essentieller Hypertonie Universität Leipzig, Dissertation 85 S.1, 85 Lit.2, 30 Abb., 7 Tab., 11 Anlagen Referat: Bluthochdruck nimmt aufgrund seiner weiten Verbreitung in der Bevölkerung und den schweren Folgeerkrankungen einen großen Stellenwert in Forschung und Klinik ein. Die Ursache für die Entstehung der häufigsten Form des Bluthochdrucks, der Essentiellen Arteriellen Hypertonie, ist bis heute unzureichend geklärt. Es gibt Erklärungsansätze, dass Hypertonie mit bestimmten Persönlichkeitsmerkmalen einhergeht. Andererseits existieren auch Beobachtungen, welche den Schluss zulassen, dass einige Charakterzüge als Risikofaktoren fungieren könnten. Ziel der vorliegenden Pilotstudie war es, einen Beitrag zur Rolle von Persönlichkeitsmerkmalen und Bewältigungsstrategien bei der Entstehung einer Essentiellen Hypertonie zu leisten. Die vorliegende Arbeit ist Teil einer übergeordneten Studie, die hierzu einen umfassenden Beitrag unter Einschluss von Genetik und Bildgebung des Gehirns leisten sollte. Es erfolgte die Diagnosesicherung einer Essentiellen Hypertonie basierend auf einer systematischen mehrmaligen Blutdruckmessung, verschiedenen Laborparametern zum Ausschluss anderer möglicher Ursachen einer arteriellen Hypertonie und einer eingehenden Anamnese. Als Hauptzielgrößen sollten neben den mittleren Blutdruckwerten vor allem Daten zu Depression, Lebenseinstellung, Ängstlichkeit, Umgang mit Ärger und Stress mittels einer Batterie von Fragebögen gewonnen werden. Hinzu kam die Erforschung der Persönlichkeitsdimensionen Neurotizismus, Extraversion, Offenheit für Erfahrungen, Verträglichkeit und Gewissenhaftigkeit. Anhand der Daten wurden die Teilnehmer in zwei Gruppen eingeteilt: Probanden mit (1) Essentieller Hypertonie sowie solche mit (2) normotonen Blutruckwerten. Bezüglich Geschlecht, Blutdruckwerten etc. erwies sich das Studienkollektiv im Hinblick auf die Bevölkerung als repräsentativ. Mit Hilfe dieser Daten konnten Gruppenvergleiche gezogen werden, des Weiteren wurden parametrische Korrelationen über die Gesamtgruppe der Probanden über mögliche Zusammenhänge zwischen verschiedenen Persönlichkeitsmerkmalen und systolischen bzw. diastolischen Blutdruckwerten durchgeführt. Die Auswertung der Hauptzielgrößen spricht dafür, dass bestimmte Persönlichkeitsfaktoren mit dem Merkmal „Essentielle Hypertonie“ assoziiert zu sein scheinen. Die vorliegenden Befunde stützen somit die Hypothese eines Zusammenhanges von Persönlichkeit und der Entwicklung einer Essentiellen Hypertonie, sollten jedoch auf Grund der geringen Stichprobengröße (n=49) vorsichtig interpretiert werden. ____________________ 1 Seitenzahl insgesamt 2 Zahl der im Literaturverzeichnis ausgewiesenen Literaturangaben:Inhaltsverzeichnis 1 Einleitung ............................................................................................................ 1 1.1 Definition, Epidemiologie, Ätiologie und Folgen der EHT ....................... 1 1.2 Kognition, Verhalten und EHT .................................................................... 3 1.3 Arbeitshypothesen und Aufgabenstellung ............................................... 6 2 Material und Methoden .................................................................................... 12 2.1 Studienpopulation ..................................................................................... 12 2.2 Studienkonzept .......................................................................................... 13 2.3 Messung des Blutdruckes und des Pulses ............................................. 16 2.4 Labordiagnostik ......................................................................................... 18 2.5 Fragebögen ................................................................................................ 18 2.5.1 Allgemeiner Fragebogen zur Anamnese und Diagnostik ....................... 19 2.5.2 Soziodemografiefragebogen .................................................................. 19 2.5.3 Psychologische Fragebögen ................................................................. 19 2.5.4 Gruppeneinteilung ................................................................................. 23 2.6 Statistische Analyse .................................................................................. 23 2.6.1 Hauptzielgrößen .................................................................................... 24 2.6.2 Nebenzielgrößen ................................................................................... 24 3 Ergebnisse ........................................................................................................ 26 3.1 Beschreibung der Studiengruppe ............................................................ 26 3.2 Hauptzielgrößen ........................................................................................ 29 3.2.1 Gruppenvergleich aller Probanden (einschließlich antihypertensiver Medikation) ............................................................................................ 29 3.2.2 Gruppenvergleich aller Probanden ohne antihypertensive Medikation .. 31 3.2.3 Korrelationstestung ................................................................................ 33 3.3 Nebenzielgrößen ........................................................................................ 36 3.3.1 Gruppenvergleich aller Probanden (einschließlich antihypertensiver Medikation) ............................................................................................ 36 3.3.2 Gruppenvergleich aller Probanden ohne antihypertensive Medikation .. 39 3.3.3 Korrelationstestung ................................................................................ 41 4 Diskussion ........................................................................................................ 46 4.1 Diskussion der Hauptzielgrößen .............................................................. 46 4.1.1 Depressivität .......................................................................................... 46 4.1.2 Angst ..................................................................................................... 48 4.1.3 Ärger ...................................................................................................... 49 4.1.4 Optimismus und Pessimismus ............................................................... 50 4.1.5 Chronischer Stress ................................................................................ 51 4.1.6 Stressbewältigung ................................................................................. 51 4.1.7 Neurotizismus ........................................................................................ 53 4.1.8 Extraversion ........................................................................................... 53 4.1.9 Offenheit für Erfahrungen ...................................................................... 54 4.1.10 Verträglichkeit ........................................................................................ 55 4.1.11 Gewissenhaftigkeit ................................................................................ 56 4.1.12 Gesamtfazit Hauptzielgrößen ................................................................ 57 4.2 Diskussion der Nebenzielgrößen ............................................................. 57 4.2.1 Körperkonstitution .................................................................................. 57 4.2.2 Sportlichkeit ........................................................................................... 58 4.2.3 Kaffeekonsum ........................................................................................ 58 4.2.4 Nikotin- und Zigarettenkonsum .............................................................. 59 4.3 Einschränkungen der Studie .................................................................... 59 4.4 Ausblick ..................................................................................................... 61 4.5 Schlussfolgerung ...................................................................................... 61 5 Zusammenfassung der Arbeit......................................................................... 63 Literaturverzeichnis................................................................................................ 66 Anlagen ................................................................................................................... 77

L’hypertension artérielle chronique représente le premier facteur de risque de l’AVC ischémique, mais elle en est aussi le principal facteur aggravant. Les mécanismes à l’origine du risque ischémique lié à l’hypertension ne sont pas encore entièrement compris. Plusieurs études ont montré l’existence d’une forte composante inflammatoire délétère impliquée dans la physiopathologie de l’hypertension. Au niveau cérébral, la présence d’une intense réactivité microgliale hypothalamique, participant à l’aggravation de la pathologie a été observé. Dans le travail présenté ici, nous nous sommes intéressés à l’impact de l’hypertension artérielle sur l’état inflammatoire du cortex cérébral, une région particulièrement touchée lors d’un AVC ischémique chez le patient. Nous avons tiré parti de la souche transgénique de souris CX3CR1GFP/+ pour l’imagerie de la dynamique microgliale, principal acteur de l’immunité cérébrale. Par une analyse in vivo réalisée en microscopie biphotonique, nous avons montré que l’hypertension induite par infusion chronique d’angiotensine-II altère la morphologie de la microglie, mais surtout sa capacité de surveillance du parenchyme cérébral et sa capacité cicatricielle. Nous avons aussi montré que ce type d’hypertension endommage la structure et la fonctionnalité des vaisseaux corticaux. L’ensemble de ces résultats pourrait expliquer, au moins en partie, la sensibilisation du cerveau aux lésions ischémiques par l’hypertension artérielle, avant même la survenue de l’AVC. / Chronic high blood pressure is ischemic stroke’s leading risk factor, but it is also its main aggravating factor. The mechanisms underlying hypertension-induced ischemic brain lesion exacerbation are not yet fully understood. Several studies highlighted the existence of a strong inflammatory component in the pathophysiology of hypertension. In the brain, the presence of intense hypothalamic microglial reactivity, contributing to the pathology worsening has been shown. In this work, we focused on the impact of high blood pressure on the inflammatory state of the cerebral cortex, a region particularly affected by ischemic stroke in the patient. We took advantage of the CX3CR1GFP/+ mice transgenic strain for imaging microglia dynamics. By using in vivo two-photon microscopy, we have shown that hypertension induced by chronic infusion of angiotensin-II alters the microglia morphology, especially its parenchymal surveilling activity and its cicatricial capacity. We have also shown that this type of hypertension disrupts the structure and the functioning of cortical vessels. All of these results can explain, at least in part, the brain sensitization to ischemic lesions under arterial hypertension, before the onset of stroke.

In recent years, behavioral approaches for the treatment of essential hypertension have received considerable research attention. Biofeedback and relaxation training have been the behavioral treatments most often used for lowering high blood pressure. The present study compared the separate use of EMG and skin temperature biofeedback in treating essential hypertension, with a combined approach utilizing both types of feedback. Twenty-one hyper- tensive subjects were randomly assigned to one of the three experimental conditions: (a) EMG biofeedback, (b) skin temperature biofeedback, or (c) both EMG and skin temperature biofeedback. In addition, a control group consisting of patients randomly chosen from a local cardiology clinic was utilized. After an eight week treatment period, a statistically significant pretest-posttest main effect was found for treatment groups for both systolic and diastolic blood pressure. However, there was no significant difference between the three treatment groups. The results did yield a significant interaction effect in comparing the treatment groups to the control group for both systolic and diastolic blood pressure reductions.