<p> This study examined the effects of isometric handgrip training (IHG) on resting blood pressure and resting arterial compliance in the carotid and brachial arteries of medicated hypertensive individuals. Previous studies found that isometric training reduced resting arterial blood pressure (RBP) in high-normal and medicated hypertensive individuals. Investigators have also found an improvement in central arterial compliance with aerobic training and a reduction in central arterial compliance with age, cardiovascular disease and resistance training. The effects of isometric training on arterial compliance have not been examined previously.</p> <p> Ten participants participated in a one-hand IHG intervention, nine participants in a two-hand IHG intervention and 5 participants served as the non-exercising controls. Each experimental group performed four, 30% maximal voluntary IHG contractions for 2 minutes, 3 days a week, for 8 weeks. The one-hand group trained only their non-dominant hand, while the two-hand group trained both hands. Measurements of resting arterial blood pressure, and cross sectional compliance of the brachial and carotid arteries were made pre-training, after four weeks of training and after the completion of the eight-week training protocol.</p> <p> There were no changes in resting arterial blood pressure after training. Mean carotid and brachial artery diameters did not change with resistance training. There were no significant changes in brachial or carotid cross sectional compliance with isometric training. In conclusion, moderated level isometric training did not elicit changes in resting arterial blood pressure and resting muscular and elastic arterial compliance in medicated hypertensive individuals compared to a non-exercising control group.</p> / Thesis / Master of Science (MSc)

Präeklampsie ist weltweit eine der Hauptursachen perinataler Morbidität und Mortalität für Mutter und Kind. Es wird vermutet, dass unterschiedliche pathophysiologische Mechanismen je nach Zeitpunkt des Auftretens der Präeklampsie vorliegen. Eine Unterscheidung zwischen früher, mittlerer und später Präeklampsie scheint relevant für Screening, klinische Manifestation und Management der Erkrankung zu sein. Ziel dieser Studie ist es die drei Typen der Präeklampsie bezüglich Risikofaktoren, Entbindungsmodalität und maternaler und neonataler Morbiditäten und Mortalitäten zu charakterisieren und zusätzlich mit denen der Gestationshypertonie und chronischen Hypertonie zu vergleichen. In einem retrospektiven Studienaufbau wurden 1089 Einlingsschwangerschaften mit hypertensiver Schwangerschaftserkrankung, deren Entbindung in einem Zeitraum von 10 Jahren (2003-2012) erfolgte, analysiert. Die maternalen und neonatalen Charakteristika der verschiedenen Gruppen hypertensiver Schwangerschaftserkrankungen wurden miteinander verglichen. Es wurden deskriptive und analytische (Chi-quadrat-Test und U-Test) statistische Methoden verwendet. Es zeigten sich signifikant unterschiedliche maternale Komorbiditäten und Risikofaktoren in den untersuchten Gruppen hypertensiver Schwangerschaftserkrankungen. Für die Mehrzahl der untersuchten Parameter waren Fälle mit Präeklampsie häufiger durch Morbidität und Mortalität betroffen waren. Patientinnen mit früher Präeklampsie fielen durch einen signifikant höheren mittleren arteriellen Druck vor Entbindung, eine erhöhte Kaiserschnittrate, eine ausgeprägtere Proteinurie und eine häufigere Korrelation zu HELLP-Syndrom, Eklampsie und vorzeitige Plazentalösung auf. Die Häufigkeit pathologischer Doppleruntersuchungen in den Arteriae uterinae und der Arteria umbilicalis verhielt sich umgekehrt proportional zur Schwangerschaftswoche zum Zeitpunkt der Entbindung. Ein nachteiliges fetales Outcome bezogen auf die perinatale und neonatale Mortalität, Beatmung über einen längeren Zeitraum als 24 Stunden, RDS-Syndrom, fetale Wachstumsrestriktion und Verlegung auf eine neonatologische Intensivstation trat unter früher Präeklampsie häufiger als unter mittlerer und bei mittlerer häufiger als unter später Präeklampsie auf. Das neonatale Outcome von Feten unter der 33. SSW war nicht vom Ausmaß der mütterlichen hypertensiven Erkrankung abhängig. Die späte Präeklampsie viel durch günstigere Outcomes als die Gestationshypertonie und chronische Hypertonie auf. Die Ergebnisse der Studie unterstützen die These, dass unterschiedliche pathophysiologische Mechanismen Präeklampsie bedingen können und dass frühe, mittlere und späte Präeklampsie entweder verschiedene Erkrankungen sind, oder die Präeklampsie eine Erkrankung darstellt, die durch verschiedene Einflussfaktoren ein unterschiedlich starkes Ausmaß annimmt. Das Gestationsalter ist demnach das entscheidende Kriterium für die klinische Ausprägung. Die unterschiedlichen Risikoprofile der einzelnen Formen hypertensiver Schwangerschaftserkrankungen fordern ein angepasstes klinisches Management.:I. Inhaltsverzeichnis II. Abkürzungsverzeichnis 1 Einleitung 1 2 Grundlagen 3 2.1 Hypertensive Schwangerschaftserkrankungen 3 2.1.1 Begriffe und Definitionen 3 2.1.2 Chronische Hypertonie 4 2.1.3 Gestationshypertonie 5 2.1.4 Präeklampsie 5 2.1.4.1 Epidemiologie 5 2.1.4.2 Pathogenese 6 2.1.4.3 Prädisposition und Risikofaktoren 7 2.1.4.4 Maternale Morbidität und Mortalität 8 2.1.4.5 Screening 9 2.1.4.6 Prävention 10 2.1.4.7 Management 11 2.2 Aspekte des fetalen Outcomes 12 2.2.1 Frühgeburtlichkeit 13 2.2.2 Fetale Wachstumsrestriktion 14 2.2.3 Totgeburt, neonatale und perinatale Mortalität 15 2.2.4 Fetale Komplikationen 15 2.3 Dopplersonographie in der Schwangerschaft 18 2.3.1 Aa. uterinae 19 2.3.2 Arteria umbilicalis 20 2.3.3 Arteria cerebri media 20 2.3.4 Ductus venosus 20 3 Material und Methoden 22 3.1 Maternale Variablen 22 3.2 Fetale und neonatale Variablen 24 3.3 Statistische Auswertung 25 3.3.1 Deskriptive Statistik 25 3.3.2 Analytische Statistik 25 4 Ergebnisse 27 4.1 Demographische Daten 28 4.2 Maternale Risikofaktoren 28 4.2.1 Body-Mass-Index 30 4.2.2 Alter 30 4.2.3 Parität 31 4.2.4 Diabetes 31 4.2.5 Nikotinabusus 32 4.3 Maternale Vorerkrankungen und Komorbiditäten 32 4.3.1 Depression, Asthma und chronisch entzündliche Darmerkrankungen 32 4.3.2 Thrombembolische Ereignisse 32 4.3.3 Nierenerkrankungen 33 4.3.4 Chronische Hypertonie 33 4.4 Schwangerschaftsbezogene Risikofaktoren 33 4.4.1 Pulsatilitätsindex der Arteria uterina 33 4.4.2 Konzeption 35 4.5 Kindliches Geschlecht 35 4.6 Entbindung – Geburtsmodus und Indikation 35 4.7 Maternale Komplikationen 37 4.7.1 HELLP-Syndrom 38 4.7.2 Eklampsie 41 4.7.3 Schwere Präeklampsie 41 4.7.4 Proteinurie 41 4.8 Maternale Mortalität 42 4.9 Das fetale Outcome 43 4.9.1 Wachstumsrestriktion und small for gestational age 45 4.9.1.1 Distribution 45 4.9.1.2 Outcome 47 4.9.2 Frühgeborene vor der vollendeten 33. SSW 49 4.9.2.1 Maternale Aspekte 50 4.9.2.2 Doppleruntersuchungen und Lungenreifeinduktion 50 4.9.2.3 Geburtsparameter 51 4.9.2.4 Geburtsgewicht und intrauterine Wachstumsrestriktion 53 5 Diskussion 55 5.1 Analyse der maternalen Faktoren 55 5.1.1 Analyse der Risikofaktoren und anderer Anamneseparameter 55 5.1.2 Analyse des Geburtsmodus oder der -indikation 57 5.1.3 Analyse der Patientinnen mit chronischer Hypertonie 58 5.1.4 Analyse der Patientinnen mit Gestationshypertonie 59 5.1.5 Analyse der prädiktiven Aussagekraft der Dopplersonographie der Aa uterinae für die Entwicklung einer Präeklampsie 60 5.1.6 Analyse der Komplikationen der Präeklampsie 61 5.2 Analyse des fetalen Outcomes 63 5.2.1 Analyse des fetalen Outcomes unter Gestationshypertonie 63 5.2.2 Analyse des fetalen Outcomes unter chronischer Hypertonie 64 5.2.3 Analyse des fetalen Outcomes unter Präeklampsie 66 5.2.4 Fetale Wachstumsrestriktion und Präeklampsie 67 5.2.5 Subanalyse der Feten mit Geburt vor der 33. SSW 69 5.3 Limitierung und Einordnung der Ergebnisse 71 6 Zusammenfassung 74 7 Literaturverzeichnis 77 8 Anhang 95 8.1 Tabellenverzeichnis 95 8.2 Abbildungsverzeichnis 97 III. Danksagung

Bone-Morphogenetic-Proteine besitzen eine umfangreiche Funktion in der Embryo- und Organogenese sowie bei der Gewebsregeneration im adulten Organismus. BMP-7 ist an der Nephrogenese beteiligt und besitzt protektive und regenerative Fähigkeiten in der adulten Niere. Das eng verwandte BMP-5 ist ebenfalls an der Nephrogenese beteiligt, wurde aber bisher in der adulten humanen Niere nicht untersucht. BMP-2 ist in der Embryogenese unabdingbar. Es induziert die Differenzierung, Migration und Proliferation embryonaler Stammzellen und ist essentiell in der Knochenentwicklung. Die Rolle von BMP-2 in der adulten Niere ist unklar. Ziel dieser Arbeit war es, die Expression, Funktion und Regulation von BMP-2 und BMP-5 in der adulten humanen Niere, bei der hypertensiven Nephrosklerose und in verschiedenen renalen Zelllinien zu untersuchen.

Thesis (MMed (Obstetrics and Gynaecology))--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: Introduction: Hypertensive disease is one of the cardinal causes of maternal morbidity and mortality in South Africa. According to the National Confidential Enquiry into Maternal Deaths (NCEMD) report for 2005-2007, the “big five” causes of maternal death have remained the same as in the previous triennium, with hypertensive disease in second place, being the causative factor in 15.7% of cases.1 Women under 20 years of age were at greater risk of dying due to complications of hypertension. In this light, the early identification and treatment of hypertensive disease remains important priorities in improving maternal care. Various serum markers have been studied to identify women at risk of pre-eclampsia, including biological markers and genetic factors.2 It is also well known that chronic hypertension is one of the major predisposing factors to the development pre-eclampsia.2 A continued search for a genetic screening test to assist in early diagnosis could facilitate a reduction of maternal morbidity and mortality. Aims: The aim of this project is to determine the prevalence of the R563Q mutation of the -subunit of the epithelial sodium channel (-ENaC) gene in a cohort of primigravid women with hypertensive disease in pregnancy and to compare pregnancy outcomes in this group of hypertensive patients to those not identified to be carriers of the mutation. Methodology: A retrospectively collected study cohort of patients with early onset pre-eclampsia, obtained from pooled samples and data from the GAP study (Genetic Aspects of Pre-eclampsia, project number C99/025), was used. The planned sample size was 200, with 200 controls who were ethnic-matched, normotensive women. Exclusion criteria were gestation 34 weeks, multiple pregnancy, known underlying collagen vascular disease and type I Diabetes Mellitus. Outcome criteria: The pregnancy outcomes were analysed with respect to the degree of hypertensive disease and related complications (maternal, placental and neonatal). Results: Blood samples form 104 patients and 80 control samples were analysed. Pre-eclamptic patients were significantly younger than controls (p<0.0001). The presence of the mutation was not significantly increased in the pre-eclamptic group (p=0.33). The mutation bearers did not exhibit a significant tendency towards a specific degree of pre-eclampsia (p=0.51). There were no significant differences in the other studied maternal or fetal outcome measures. A composite outcome (the presence of 1 adverse outcome compared to no adverse outcome) was created which did not differ between the mutation positive and negative pre-eclamptic patients. Data of the index study was combined with the data form a prior relevant study9 and combined odds ratios were calculated. The increased mutation frequency amongst pre-eclamptics compared to healthy controls then remains significant, OR 2.57(95%CI 1.23-5.36). Conclusion: In this study the R563Q mutation of the ß-subunit of the epithelial sodium channel gene was not linked to pre-eclampsia. No significant negative correlation could be established between the presence of the R563Q mutation and the outcomes of pre-eclampsia. Further research aimed at chronic hypertensive patients in pregnancy and unstable pre-eclampsia in larger study groups could shed more light on the relation between the mutation and the pre-eclamptic phenotype. / AFRIKAANSE OPSOMMING: Inleiding: Hipertensie-verwante siektes is een van die hoof oorsake van moederlike morbiditeit en mortaliteit in Suid-Afrika. Volgens die Nasionale Vertroulike Ondersoek insake Moederlike Sterftes (NCEMD) verslag vir 2005-2007, is die “groot vyf” oorsake van moedersterftes dieselfe as in die vorige triënnium, met hipertensie-verwante siektes in tweede plek, as die oorsaak van 15.7 % van die sterfgevalle. 1 Vroue jonger as 20 jaar het ‘n groter risiko om te sterf aan die komplikasies van hipertensie-verwante siektes. In die lig hiervan is die vroeë identifikasie en behandeling van hipertensie-verwante siektes ‘n priorteit in die verbetering van moedersorg. Verskeie serum merkers is al bestudeer met die hoop om vroue met verhoogde risiko vir die ontwikkelling van pre-eklampsie te identifiseer, wat biologiese merkers en genetiese faktore insluit. 2 Dit is ook welbekend dat chroniese hipertensie een van die hoof predisponerende faktore is vir die ontwilkkeling van pre-eklampsie.2 ‘n Voortgesette soektog na ‘n genetiese siftingstoets wat kan bydra tot vroeë identifisering, sou moederlike morbiditeit en mortaliteit kon verminder. Doelwittle: Die doelwit van hierdie projek is om die prevalensie van die R563Q mutasie van die -subeenheid van die epiteliële natrium kanaal (-ENaC) geen te bepaal in ‘n kohort primigravida vroue met hipertensie-verwante siekte in swangerskap en om die swangerskapsuitkomste van hierdie groep te vergelyk met pasiente wat nie draers van die mutasie is nie. Metodologie: ‘n Retrospektief versamelde studie kohort met vroeë aankoms pre-eklampsie, verkry van die monsterbank en data van die GAP studie (Genetic Aspects of Pre-eclampsia, projek nommer C99/025) is gebruik. Die beplande steekproef grootte was 200, met 200 kontroles, wat etnies- en ouderdomvergelykbare normotensiewe vroue was. Uitsluitingskriteria was gestasie 34 weke, onderliggende bindweefselsiekte en tipe I Diabetes Mellitus. Uitkomskriteria: Swangerskap uitkomste was geanaliseer met betrekking tot die graad van hipertensiewe siekte en verwante kompliksies (moederlik, plasentaal en neonataal). Resultate: Bloed monsters van 104 pasiënte en 80 kontroles is ontleed. Pre-eklampsie pasiënte was betekenisvol jonger as kontroles (p<0.0001). Die teenwoordigheid van die mutasie was nie betekenisvol verhoog in die pre-eklampsie groep nie (p=0.33). Die mutasie-draers het nie ‘n geneigdheid tot ‘n spesifieke graad van pre-eklampsie getoon nie (p=0.51). Daar was geen betekenisvolle verskille tussen die ander moederlike of fetale uitkomste wat bestudeer is nie. ‘n Gesamentlike uitkoms (teenwoordigheid van 1 swak uitkoms vergeleke met geen swak uitkoms) is geskep; daar was geen verskil tussen die mutasie-positief en negatiewe pasiënte met pre-eklampsie nie. Data van die indeks studie en relevante data uit ‘n vorige studie9 is saamgevoeg en die gesamentlike kansverhouding is bereken. Die verhoogde mutasie frekwensie onder pasiënte met pre-eklampsie vergeleke met gesonde kontroles was betekenisvol, KV 2.57(95%VI 1.23 - 5.36). Gevolgtrekking: In hierdie projek was daar nie ‘n verband tussen die R563Q mutasie van die -subeenheid van die epiteliële natrium kanaal (-ENaC) geen en pre-eklampsie nie. Geen betekenisvolle negatiewe korrelasie tussen die R563Q mutasie en pre-eklampsie uitkomste kon aangetoon word nie. Verdere navorsing gerig op pasiënte met chroniese hipertensie of akute, onstabiele pre-eklampsie in groter studiegroepe kan die verband tussen die mutasie en die pre-eklampsie fenotipe moontlik beter toelig.

Despite advances in obstetric care, hypertensive disorders continue to complicate pregnancies at a high rate. Worldwide, hypertensive disorders affect up to 10% of pregnancies. The United States has seen a 25% increase in the incidence of hypertensive disorders over the last two decades (American College of Obstetricians and Gynecologists, 2017). These complications constitute one of the greatest causes of maternal and perinatal morbidity and mortality with an estimated 50,000 to 60,000 deaths per year across the world (American College of Obstetricians and Gynecologists, 2017). Although the etiology of hypertensive disorders remains unclear, there may be an association with both maternal biological and psychological distress in the development of the disorder. Although both distress and biomarkers have been identified in association with a hypertensive disorder, little data exist examining the components of distress and the alterations in biomarkers in women developing these disorders. Due to the limited evidence, a critical need exists to examine the relationship of perceived maternal distress and biomarker measures in the development of a hypertensive disorder during pregnancy in order to better understand this phenomenon. The purposes of this dissertation were to: 1) understand the experience of having a hypertensive disorder during pregnancy; 2) to investigate the association of perceived stress and changes in immune response via biomarker measures in women who develop a hypertensive disorder during pregnancy; 3) to review, summarize, and evaluate the literature examining the relationship between perceived maternal distress (stress, anxiety, and depression) and the development of a hypertensive disorder; and 4) to investigate the association of perceived distress in the development of a hypertensive disorder during pregnancy. Data obtained from a qualitative study of women with a hypertensive disorder during pregnancy placed on bed rest reported several stressors associated with the experience. These stressors related to differing and often conflicting management plans by different providers and not feeling providers heard their concerns. The evidence supports these women experience stress during this pregnancy complication. Analysis of data obtained at each trimester of pregnancy did identify differences in biomarker levels based on perceived stress and women with a hypertensive disorder and those without a hypertensive disorder. Evidence from a systematic review of literature supporting maternal distress in the development of a hypertensive disorder was mixed. However, few studies existed and of those reviewed, most lacked rigor. Analysis of data obtained early and late in pregnancy did not indicate a relationship between psychological distress and the development of a hypertensive disorder in pregnancy. Women with a higher BMI were 12% more likely to develop a hypertensive disorder. The factors associated with the development of a hypertensive disorder are complex. Maternal perceived stress and inflammatory responses differ between women with a hypertensive disorder and those without a hypertensive disorder in pregnancy; however maternal distress did not differ between groups. Body mass index was associated with the development of hypertension in pregnancy. Clinicians need to include assessment of maternal BMI as a modifiable risk factor in the development of a hypertensive disorder during pregnancy. In addition, although psychological distress was not associated with the development of a hypertensive disorder, women still suffer with components of distress. Clinicians could identify and support women experiencing distress thereby promoting a healthier pregnancy.

Student No. 0107750D M.Sc(Med) Research Report / The prescription habits of general practitioners are continually under the scrutiny of ethical critics. There are numerous factors that influence a practitioner’s decision as to which antihypertensive agents to prescribe for the treatment of hypertension. As outlined in various international and national guidelines for the management of hypertension, the recommended treatment depends on ethnicity, current life-style, diet, smoking, age, gender, family history and possible underlying or secondary conditions such as diabetes mellitus, heart failure, isolated systolic hypertension, myocardial infarction, pregnancy, and evidence of coronary artery disease (CAD), stroke or peripheral vascular disease. Currently the control of blood pressure in patients with hypertension is far from optimal with over 70% of hypertensive patients being reported as having imperfect control. A number of factors related to the patient, the practitioner or the medication may explain the high incidence of inadequate blood pressure control. One possible explanation for the poor control of blood pressure may be that practitioners fail to comply with the guidelines. Hence the aim of my study was firstly to determine whether a practitioner’s decision as to which medication to prescribe in the treatment of hypertension is influenced by the Southern African Hypertension Society Guidelines. Secondly, in an attempt to assess the validity of the results of the primary analysis, the actual prescription habits (MediCross® database) were assessed and compared to the general practitioner’s recall of their prescription habits. Questionnaires were distributed to 320 MediCross® practitioners and prescription habits were identified and substantiated by the screening of an existing MediCross® database. I chose as my sample MediCross® general practitioners, as they are demographically representative of all major urban areas in South Africa; likely to be open-minded to supporting research and answering questionnaires (as MediCross® is part of a Clinical Research Site Management Organisation); and I had access to the database of the prescriptions made by MediCross® practitioners hence enabling me to fulfil my second objective. However, it must be kept in mind that these practitioners are representative of general practitioners in urban areas only (as the title of my research report indicates). My results show that 33.1% adhere to the guidelines (when a non-conservative definition of diuretics is used); 27% have heard of the guidelines and have a copy of them. When asked to give their own opinion however, 39% thought they adhered to the guidelines. The results also show that ACE inhibitors are the most commonly prescribed drug class for uncomplicated hypertension but a comparison to a MediCross® database, of which the quality is questionable, does not support this. As the response rate to the questionnaires was only 24.7%, these results are only a pilot study; however they suggest that few general practitioners use the guidelines or even have a copy of the guidelines. This pilot study suggests that the guidelines need to be distributed more widely. Furthermore the general practitioners that responded to the questionnaire indicated that the management of hypertension is difficult in that there is no single treatment regimen appropriate for all populations and each different patient. It was also their view that clinical guidelines for the management of hypertension should more accurately reflect the uncertainty of when to initiate treatment and individual variation if they are going to take these guidelines seriously and comply with them.

INTRODUÇÃO. A hipertensão arterial sistêmica é uma doença cardiovascular comum que afeta cerca de 50 milhões de pessoas nos EUA, e um número proporcional a este no Brasil. Muitos estudos têm mostrado que diversas classes de diterpenóides exercem efeito significante sobre o sistema cardiovascular. Esses estudos apontam essa classe de metabólitos como uma fonte promissora de protótipos para o desenvolvimento de novos agentes na terapêutica cardiovascular. OBJETIVO. O presente estudo foi delineado de forma a investigar os mecanismos envolvidos no efeito cardiovascular (in vitro e in vivo) do diterpeno esclareol em ratos normotensos e hipertensos. MATERIAL E MÉTODOS. Foram utilizados ratos Wistar machos, pesando em média 250 - 300g provenientes do Biotério Central do Campus de Ribeirão Preto, Universidade de São Paulo (USP). Os animais foram acondicionados no Biotério do Departamento de Cirurgia e Anatomia, em ambiente com temperatura (22-25ºC) e ciclo claro/escuro (12:12 horas) controlados. Para a indução da hipertensão utilizou-se o modelo 2 rins - 1 clipe (artéria renal esquerda). A pressão arterial não invasiva da cauda foi avaliada utilizando-se um manguito, conectado a um sensor para registro de pressão arterial sistólica (Kent Scientific Corporation, Connecticut, USA). A monitorização da pressão arterial média foi realizada utilizando-se o MP System 100 A (BioPac System, Inc., Santa Barbara, CA, USA). A reatividade vascular in vitro foi estudada pela avaliação de curvas concentração-resposta para esclareol construídas a partir do registro de forças isométricas obtidas em anéis de aorta, com ou sem endotélio, pré-contraídos com Phe 10-7M em câmaras de órgãos (\"organ chambers\"). As dosagens indiretas de NO plasmático foram realizadas pela determinação dos níveis séricos de nitrito e nitrato utilizando-se o Sievers NOAnalizer 280i (Sievers, Boulder, CO, E.U.A.). Análise de variância de uma ou duas vias (ANOVA), seguida pelo pós-teste de Bonferroni foram realizadas para detectar possíveis diferenças entre os valores em estudo. P<0,05 foi considerado significativo. RESULTADOS. A análise do efeito do Esclareol sobre a ?PAS mostrou que, em ambos os grupos, houve uma importante redução da ?PAS. Os inibidores de óxido nítrico sintase e guanilato ciclase foram tão eficientes quanto a retirada do endotélio, em inibir o relaxamento induzido pelo esclareol. A análise das dosagens do NO plasmático mostrou que não houve diferença significante entre os grupos. CONCLUSÃO. A partir dos dados obtidos no presente estudo, conclui-se que o esclareol mostrou-se promissor quanto aos seus efeitos vasodilatadores, tanto in vivo quanto in vitro. Apesar disso, o esclareol não promoveu alterações do NO, possivelmente devido ao método utilizado / INTRODUCTION. High Blood Pressure is a common cardiovascular disease that affects about 50 million people in the US, and a proportionate number to this in Brazil. Many studies have shown that many diterpenoid classes exert significant effect on the cardiovascular system. These studies suggest these metabolites class as a promising source prototype for the development of new agents in the cardiovascular therapy. OBJECTIVE. This study was designed to investigate the mechanisms involved in cardiovascular effect (in vitro and in vivo) of diterpene esclareol in normotensive and hypertensive rats. MATERIAL AND METHODS. Male Wistar rats were used, weighing an average of 250 - 300g from the Central Animal Facility of the Campus of Ribeirão Preto, University of São Paulo (USP). The animals were kept in the animal house of the Department of Surgery and Anatomy in temperature environment (22-25ºC) and light / dark cycle (12:12 hours) controlled. For the induction of hypertension, the model was used two kidney - one clip (left renal artery). The tail noninvasive blood pressure was measured using a cuff, connected to a sensor for systolic arterial blood pressure ((Kent Scientific Corporation, Connecticut, USA). The monitoring of mean arterial blood pressure was measured using MP System 100 A (BioPac System, Inc., Santa Barbara, CA, USA). The in vitro vascular reactivity was evaluated by measuring concentration-response curves for sclareol built from the record of isometric forces obtained in aortic rings with or without endothelium precontracted with Phe 10-7M in organ chambers. The indirect plasma measurements of NO were carried out by determination of serum levels of nitrite and nitrate using the Sievers NOAnalizer 280i (Sievers, Boulder, CO, USA). One or two-way analysis of variance (ANOVA) followed by Bonferroni posttests were performed to detect possible differences between the values in the study. P <0.05 was considered significant. RESULTS. The analysis of the effect of Esclareol on ?PAS showed that there was a significant reduction in ?PAS in both groups. The nitric oxide synthase and soluble guanylate cyclase inhibitors were as efficient as the removal of endothelium, to inhibit relaxation induced by the sclareol. Analysis of the strengths of plasmatic showed no significant difference between groups. CONCLUSION. From the data obtained in this study, it is concluded that the sclareol showed promise as to their vasodilator effects, both in vivo and in-vitro. Nevertheless, the sclareol showed no change of NO, possibly due to the method used

Made available in DSpace on 2016-04-04T18:27:30Z (GMT). No. of bitstreams: 1 Flavia Urbini.pdf: 268291 bytes, checksum: 8e79c56903cfc5e622f2251b90bd83fc (MD5) Previous issue date: 2007-02-07 / Pontif?cia Universidade Cat?lica de Campinas / Hypertension has been studied by many health professionals. According to many researches hypertension is caused by an association of many different risk factors, and stress could be one of them. There are several of studies that demonstrate stress effects on hypertensive patients. The purpose of this study was to verify the possible association between stressful events and hypertensive crises occurrence. This sample was comprised by 20 women whose age was around 45-55. All data were collected in one-section interview with hypertensive urgency patients, and the instruments used were: The Inventory of Stress Symptoms (ISSL), and the Stress Sources Scale. According to the results, most of the subjects had the stress diagnosis, and the present stressors average in the last 6 months was 3,15. The most frequent stressor found was threat to personal integrity These results suggest that new and larger researches are necessary to deeply understand the influence of stressful events on the hypertensive urgency occurrence. / A hipertens?o tem sido muito estudada pelos profissionais da ?rea da sa?de. Considera-se a hipertens?o uma doen?a causada pela associa??o de diferentes fatores de risco, entre eles o stress. Os efeitos do stress no paciente hipertenso, assim como em pacientes com outras doen?as, v?m merecendo aten??o, considerando-se sua grande influ?ncia. O objetivo deste estudo foi avaliar a poss?vel rela??o entre os eventos estressantes e a ocorr?ncia da urg?ncia hipertensiva. Participaram vinte mulheres com idade m?dia de 45-55 nos. Os dados foram coletados em um ?nico encontro com o paciente em urg?ncia hipertensiva. Foram utilizados os seguintes instrumentos: Invent?rio de Sintomas de Stress para Adultos e Escala de Fontes de Stress. A maioria dos participantes apresentou o diagn?stico de stress e a m?dia do n?mero de fontes estressoras presentes nos ?ltimos seis meses foi 3,15. O tipo de fonte de stress mais freq?ente foi a amea?a ? integridade. Esses resultados sugerem novas pesquisas nessa ?rea com maior n?mero de participantes para uma melhor compreens?o da influ?ncia dos eventos estressantes na ocorr?ncia da urg?ncia hipertensiva.

The aim of this thesis was to investigate the effect of antihypertensive therapy on vascular function and placental markers in hypertensive disorders in pregnancy (HTD). We prospectively studied 208 women at the Homerton and University College London Hospitals. Vascular and serum markers were measured in 80 with HTD [51 pre-eclampsia (PE), 29 gestational hypertension (GH)] and 80 normotensive controls. The same markers were measured in placental samples from another 48 women (14 PE, 10 GH, 24 controls). Pulse wave analysis indices [augmentation pressure (AP) and augmentation index at heart rate 75/minute (Aix-75)], serum and placental concentrations of soluble fms-like tyrosine-kinase-1 (sFlt-1), soluble endoglin (sEng), placental growth factor (PIGF), vascular endothelial growth factor (VEGF), inhibin A, activin A, and uterine artery Doppler were measured before, and 24-48 hours after, initiating antihypertensive therapy. The three study groups were compared using ANOVA multiple comparisons with Bonferroni post hoc testing. Marker levels before and after antihypertensives were compared using paired t-test. In both pre-eclampsia (P < 0.0001) and gestational hypertension (P < 0.05), serum sFlt-1 was increased and PIGF reduced (P < 0.001) compared to controls. Serum sEng levels were also increased in pre-eclampsia. Placental sFlt-1 and sEng were significantly higher (P < 0.0001), and PIGF lower (P = 0.008), in pre-eclampsia compared to controls and gestational hypertension. Antihypertensive therapy was associated with a significant fall in serum and placental sFlt-1 and sEng in pre-eclampsia only (P < 0.05). In pre-eclampsia, but not gestational hypertension, treatment was associated with significantly (P < 0.05) lower serum and placental inhibin A and activin A. In women with pre-eclampsia or gestational hypertension, both AP (P < 0.0001 and P < 0.05) and Aix-75 (P < 0.0001 and P < 0.001) were significantly higher than controls. Antihypertensive therapy resulted in a significant fall in both AP and Aix-75 in pre-eclampsia only (P < 0.0001). Anti hypertensive drugs may have an effect on the pathophysiology of pre-eclampsia other than their known anti hypertensive action.

Introdução: As doenças hipertensivas da gestação (DHG) são a principal causa de morte materna em todo o mundo. A pré-eclâmpsia ocorre em 3-5% das gestações, acrescentando maior morbimortalidade. Apesar da importância em saúde pública dessa patologia, sua patogênese não está totalmente esclarecida. Acredita-se que uma disfunção na placentação ocasione um estado de estresse oxidativo, contribuindo para manifestação clínica da doença. O selênio é um antioxidante presente no organismo cujas concentrações séricas tendem a diminuir na gestação normal, e a sua deficiência vem sendo relacionada às DHG. Entretanto, estudos prévios mostram resultados conflitantes. O objetivo deste estudo é correlacionar os níveis séricos de selênio com DHG na nossa população, considerando um possível fator de proteção deste mineral. Métodos: Foi realizado um estudo caso-controle, incluindo 32 gestantes normotensas, 20 hipertensas (hipertensão crônica e gestacional) e 38 pacientes com pré-eclâmpsia. Todas pacientes foram oriundas do pré-natal ou admissão obstétrica do Hospital de Clínicas de Porto Alegre. O selênio sérico foi dosado no momento da inclusão do estudo. As pacientes foram acompanhadas até o momento da alta após o parto. O nível de significância adotado foi de 5% (p≤0,05) e as análises foram realizadas no programa SPSS versão 18. Resultados: As pacientes não diferiram quanto à idade materna, etnicidade, anos de estudo, paridade e prevalência de tabagismo. Pacientes normotensas apresentaram menor índice de massa corporal e foram incluídas no estudo mais precocemente. Além disso, estas pacientes apresentaram maior prevalência de outras comorbidades, excluindo hipertensão. Pacientes com pré-eclâmpsia tiveram níveis de pressão arterial sistólica mais altos no momento da admissão. Uso contínuo de medicações e história de DHG em gestações anteriores foi mais comum no grupo de pacientes com pré-eclâmpsia. Os níveis séricos de selênio não apresentaram diferença significativa entre os grupos, sendo uma média de 56,4±15,3μg/L no grupo controle, 53,2±15,2μg/L no grupo hipertensão e 53,3±16,8μg/L no grupo com pré-eclâmpsia (P=0,67). Das pacientes com préeclâmpsia, 52,6% apresentaram pré-eclâmpsia grave. Os níveis séricos de selênio destas pacientes também não diferiram significativamente do grupo controle (P=0,77). Pré-eclâmpsia foi associada a interrupção mais precoce da gestação e menor peso de nascimento (P<0,05), entretanto não houve diferença significativa entre os outros desfechos estudados. Conclusão: Não houve diferença significativa na concentração de selênio sérico entre gestantes normotensas e gestantes com doenças hipertensivas da gestação, não sendo possível estabelecer um fator de proteção. / Introduction: The hypertensive disorders of pregnancy (HDP) are the leading cause of maternal death in the world. Preeclampsia occurs in 3-5% of pregnancies, adding greater morbidity and mortality. Despite the importance of this disease in public health, its pathogenesis is not fully understood. It is believed that a dysfunction in the placentation process leads to oxidative stress, contributing to the clinical manifestation of the disease. Selenium is an antioxidant present in the body, which serum concentrations tend to decrease in normal pregnancy. Its deficiency has been related to HDP. However, previous studies have shown conflicting results. The aim of this study is to correlate serum selenium levels with HDP in our population, considering a possible protective factor of this mineral. Methods: We conducted a case-control study, including 32 normotensive pregnant women, 20 with hypertension (chronic and gestational hypertension) and 38 patients with preeclampsia. All patients were derived from antenatal or obstetric admission of Hospital de Clínicas de Porto Alegre. Serum selenium was measured at the time of inclusion in the study. Patients were followed until hospital discharge after delivery. The significance level was 5% (p≤0.05) and analyzes were performed using SPSS version 18. Results: The patients did not differ with regard to maternal age, ethnicity, years of education, parity, and smoking prevalence. Normotensive patients had lower body mass index and were included in the study earlier. In addition, these patients had a higher prevalence of other comorbidities excluding hypertension. Patients with preeclampsia had higher levels of systolic blood pressure on admission. Continuous use of medication and HDP history in previous pregnancies were more common in patients with preeclampsia. Serum selenium levels were not significantly different between groups, with an average of 56.4 ± 15,3 μg/L in the control group, 53.2 ± 15,2 μg/L in the hypertension group and 53.3 ± 16,8 μg/L in the group with preeclampsia (P=0.67). Of patients with preeclampsia, 52.6% had severe preeclampsia. Serum selenium levels of these patients did not differ significantly from the control group (P=0.77). Preeclampsia was associated with earlier interruption of pregnancy and lower birth weight (P<0.05). There was no significant difference between other outcomes studied. Conclusion: There was no significant difference in the concentration of serum selenium between normotensive pregnant women and pregnant women with hypertensive disorders of pregnancy, thus not being possible to establish selenium as a protective factor.