The work presented in this thesis examines the role of cardiac sympathetic signalling in the development and maintenance of hypertension in the spontaneously hypertensive rat (SHR); and the role the norepinephrine re-uptake transporter (NET) plays in the sympathetic phenotype during hypertension. <b>Chapter One</b>: reviews (i) cardiac impairment observed in hypertension, (ii) the mechanisms underlying sympathetic neurotransmission and signal termination, (iii) the structure, function, mechanism of action, and role of the norepinephrine (NE) re-uptake transporter in a number of diseases related to sympathetic dysfunction including hypertension. <b>Chapter Two</b>: comprises a detailed rational for the approach taken to; (i) record NET rate in single isolated cells from major sympathetic ganglia using a novel fluorescent assay (NTUA); (ii) measure norepinephrine release from isolated sympathetic cells using a method of carbon fibre based amperometry; (iii) measure autonomic function on living tissue in-vivo and in-vitro using organ bath and whole animal preparations; (iv) quantification of protein expression and protein levels within single cells and isolated ganglia. <b>Chapter Three</b>: examined the cardiac autonomic phenotype of the young pre-hypertensive SHR. Baseline haemodynamics were comparable between the SHR and age matched WKY controls, apart from in-vivo heart rate which the SHR displayed a small, but significant tachycardia. Release of sympathetic neurotransmitter NE, and the co-transmitter NPY were also elevated in the young SHR compared to WKY even though the SHR showed no elevation in arterial blood pressure at this age. Tyrosine hydroxylase levels were unaltered. ³H-NE release studies also revealed there may be a dysfunction in NET in the SHR at this age, as DMI treatment normalised the difference in ³H-NE overflow between the SHR and WKY. <b>Chapter Four</b>: described an investigation in to the activity of the NE re-uptake transporter between older, SHR with established hypertension and age matched normotensive WKY. A novel fluorescent assay of the monoamine transporter family was used to monitor NET activity within isolated sympathetic cells from three ganglia associated with hypertension. Direct evidence for the first time is reported that NET activity was lower in cardiac stellate neurons of the SHR compared to the WKY, but not in the other ganglia tested (superior cervical ganglion (SCG) – vascular innervation of head and neck, and celiac/superior mesenteric ganglia (CG/SMG)– renal and abdominal organs). The data support the notion that NET is regulated in a site-specific fashion, which may account for the sympathetic heterogeneity of NE spillover reported in humans. <b>Chapter Five</b>: examined differences in NET activity and expression levels between four-week-old pre-hypertensive SHR and age matched WKY. The NTUA assay revealed a significantly lower rate of NET activity within stellate neurons of the young SHR compared to WKY, with no difference in NET protein expression. No difference again was seen in the other ganglia. The SCG was the only ganglia in which NET significantly decreased with age, indicating the NET dysregulation within the vasculature may develop at a later stage of hypertension than observed in cardiac ganglia. <b>Chapter Six</b>: examined the ability to modulate NET activity in WKY and SHR stellate neurons in response to a number of pharmacological agents that stimulate cGMP (BNP, SNP, 8-Br-cGMP) and inhibition of PKC. These were agents previously implicated in NET modulation in other cell types. All activators of cGMP reduced NET rate to a similar degree in the WKY. No change in NET rate was observed in the SHR, indicating that NET modulation either intrinsically, and/or receptor membrane insertion, was faulty in the SHR. PKC inhibition increased NET rate in both groups. <b>Chapter Seven</b>: is a concluding discussion summarising the main findings from this thesis, placing them in to physiological context, and discusses avenues of further research.

Orientador: Débora Simões de Almeida Colombari / Banca: Colin Summers / Banca: José Antunes-Rodrigues / Banca: Marco Antonio Peliky Fontes / Banca: Juliana Irani Fratucci De Gobbi / Resumo: É de extrema importância para o funcionamento do organismo a manutenção da osmolaridade e volume dos líquidos corporais. O sistema nervoso central (SNC) tem um papel fundamental para esta manuntenção. O núcleo do trato solitário (NTS) é o sítio primário das aferências cardiovasculares e de osmorreceptores periféricos e se projeta à areas prosencefálicas envolvidas com a regulação cardiovascular e do equilíbrio hidroeletrolítico. Desta forma, o NTS pode fazer a ligação entre as aferências viscerais e o SNC e participar dos ajustes necessários a regulação da osmolaridade e da volemia. A maior porção dos neurônios do grupamento catelocaminérgicos A2 do bulbo está localizada na porção comissural no NTS (NTScom). Assim, os objetivos deste estudo foram: a) estudar os efeitos na pressão arterial, na ingestão de água e na excreção renal subsequentes a administração de NaCl 2 M, estímulo osmótico agudo, em ratos com lesão seletiva dos neurônios A2 do NTScom; b) estudar os efeitos na expressão da proteína c-FOS subsequente a administração de NaCl 2 M, em ratos com lesão seletiva dos neurônios A2 do NTScom, c) estudar alterações na expressão de RNAm no NTS após a administração de NaCl 2 M, d) estudar os efeitos na pressão arterial subsequentes a hemorragia hipotensiva, em ratos com lesão seletiva dos neurônios A2 do NTScom. Ratos Holtzman (280-320 g) ou ratos Sprague-Dawley (230-280 g) foram utilizados neste estudo. Para a lesão seletiva dos neurônios A2 do NTScom ou lesão fictícia (LF), os animais foram submetidos a uma craniotomia parcial e a superfície dorsal do bulbo foi exposta. A lesão seletiva dos neurônios noradredérgicos foi realizada por meio da injeção no... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The central nervous system has an important role controlling the mechanisms involved in the regulation of body fluid osmolality. The nucleus of the solitary tract (NTS) is the primary site of cardiovascular and peripheral osmoreceptors afferents and projects to prosencephalic areas involved in hydroelectrolytic balance and cardiovascular regulation. The great part of the catecholaminergic neurons of the A2 group is located in the commissural part of the NTS (NTScom). Thus, the aims of this study were: a) to verify the effects in the arterial pressure, water intake and renal excretion observed after intragastric (ig) 2 M NaCl in rats with lesion of the A2 neurons of the NTScom, b) to verify the effects in the c-Fos expression after ig 2 M NaCl in rats with lesion of the A2 neurons of the NTScom, c) to study changes in gene expression on NTS after ig 2 M NaCl, d) to study the effects in arterial pressure after hypotensive hemorrhage in rats with lesion of the A2 neurons of the NTScom.Male Holtzman rats (280-320 g) or Sprague-Dawley (250-280 g) were used. For the A2 lesion of the NTScom, a partial craniotomy of the occipital bone was performed, and the dorsal surface of the brainstem was exposed. The lesion was performed by the injection of the toxine anti-dopamine-β-hydroxylase-saporin into the NTScom to destroy A2 neurons in this region. Sham lesioned rats anti-IgG-saporin was injected into the NTScom. We observed that in A2 lesioned rats, ig 2 M NaCl induced a vasopressin dependent-pressor response, for at least 60 min. The water intake induced by sodium overload was also incremented in A2 lesioned rats, however the natriuresis and dieresis after 2 M NaCl were similar in both groups. After 2 M NaCl... (Complete abstract click electronic access below) / Doutor

Made available in DSpace on 2014-06-11T19:29:52Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-08-18Bitstream added on 2014-06-13T20:39:44Z : No. of bitstreams: 1 moura_mdr_me_botfm.pdf: 476585 bytes, checksum: 619c85e4fc295e56f3b00ad14f5ccdbe (MD5) / Fundação de Ensino e Pesquisa em Ciências da Saúde (FEPECS) / Os dados do Ministério da Saúde mostram a hipertensão na gestação como a maior causa de morte materna no Brasil sendo assinalada também como a maior causa de óbito fetal ou do recém-nascido. Esses alarmantes dados nacionais mostram a importância do conhecimento desta patologia gestacional tanto para obstetras como neonatologistas. Dentre as síndromes hipertensivas gestacionais, especial atenção deve ser dada à pré-eclâmpsia ou doença hipertensiva específica da gravidez que ocorre como forma isolada ou associada à hipertensão arterial crônica, pois esta está ligada aos piores resultados maternos e perinatais. O adequado controle pré-natal com seguimento rigoroso da gestante é a única forma de reduzir a mortalidade materna e perinatal. O uso de recurso de imagem como a dopplervelocimetria permite ao examinador diagnosticar insuficiência placentária e avaliar as condições circulatórias materno-fetal de forma segura e não invasiva. A decisão pela antecipação do nascimento nestas circunstâncias nem sempre é uma proposta segura. A equipe médica e familiares devem estar ciente dos riscos que um recém nascido além de prematuro, apresenta na maioria das vezes grave restrição do crescimento intrauterino. A UTI Neonatal deve estar preparada para oferecer cuidado intensivo e multiprofissional que permita diagnóstico e tratamento das mais variadas complicações, bem como a disponibilidade de recursos tecnológicos avançados são fundamentais para a melhoria dos resultados neonatais, tanto na sobrevivência, como na qualidade de vida / Data from the Ministry of Health showed that hypertension in pregnancy as a major cause of maternal death in Brazil is also noted as a major cause of stillbirth or newborns death.These alarming national data show the importance of knowledge of this gestation pathology to obstetricians and neonatologists. Among the hypertensive disorders of pregnancy special attention should be given to pre-eclampsia this hypertensive disorders of pregnancy can occurs as isolated or associated with chronic hypertension, can cause the worse maternal and perinatal outcomes. Only with a adequate prenatal and a close maternal follow up it is the only way to reduce maternal and perinatal mortality. The use of image resource as the dopplervelocimetria allows the examiner to diagnose and assess the placental maternal-fetal circulatory conditions safely and noninvasively. The decision to anticipation of the birth in these circumstances is not always a safe proposal. Medical staff and family members should be aware of the risks of a premature newborn that often presents severe intrauterine growth restriction. The NICU should be prepared to offer intensive care and multidisciplinary staff prepare to diagnosis and treatment of various complications, as well as the availability of advanced technological resources are critical to the improvement of neonatal outcomes no only in survival but in quality of life too

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / A atuaÃÃo da enfermeira nas consultas a portadores de hipertensÃo arterial, realizando aÃÃes especÃficas e intervenÃÃes sistematizadas, tem crescente importÃncia porque, nÃo raro, o cliente carece de intervenÃÃes que fogem da competÃncia de um sà profissional. Teve-se como objetivo identificar intervenÃÃes de enfermagem documentadas em prontuÃrios de portadores de hipertensÃo arterial atendidos em um serviÃo de referÃncia; detectar a freqÃÃncia do registro das intervenÃÃes; analisar, com base no Plano de ReorganizaÃÃo da AtenÃÃo à HipertensÃo Arterial e ao Diabetes Mellitus (Brasil, 2001) e nas Diretrizes Brasileiras de HipertensÃo Arterial (2006), as intervenÃÃes com freqÃÃncia igual ou superior a cinco vezes nos registros; e mapear as intervenÃÃes encontradas, segundo a ClassificaÃÃo Internacional para a PrÃtica de Enfermagem, versÃo 1. Foi realizado na cidade de Fortaleza, em uma unidade de saÃde de referÃncia em hipertensÃo arterial e diabetes mellitus, para o CearÃ. Universo constituÃdo por 3.606 prontuÃrios cadastrados de julho de 2003 a julho de 2005, no total de 704 prontuÃrios com registro do diagnÃstico de hipertensÃo arterial. Entre esses, 175 prontuÃrios atenderam aos critÃrios de inclusÃo: ser prontuÃrio de paciente portador do diagnÃstico de hipertensÃo arterial primÃria ou essencial, sem outras morbidades, como neoplasias, doenÃas hematolÃgicas, neuro-psiquiÃtricas, Ãsseas, metabÃlicas e renais; estar cadastrado, e em vigÃncia desde julho de 2003; independente de sexo e idade e ter registro de, pelo menos, uma consulta de enfermagem. Os dados foram coletados nos prontuÃrios pela anÃlise dos registros das consultas de enfermagem realizadas de dezembro de 2005 a fevereiro de 2006. Utilizou-se um formulÃrio que tinha como eixo as questÃes necessÃrias para atingir os objetivos propostos. Nos 175 prontuÃrios, houve registro de 259 consultas de enfermagem (mÃdia: 1,48). Em todas havia registros de intervenÃÃes, no total de 10 aÃÃes de enfermagem e 972 registros de intervenÃÃes, com uma mÃdia de 3,7 intervenÃÃes por consulta. As aÃÃes presentes foram: verificar (819), orientar (71), encaminhar (65), ensinar (7), manter (5), estimular (1), conscientizar (1), evitar (1), vigiar (1) e solicitar (1). Na aÃÃo de verificar destacaram-se intervenÃÃes que ocorreram com uma freqÃÃncia igual ou superior a cinco vezes: pressÃo arterial (257), peso (217), glicemia (212), altura (86); seguindo-se pelas intervenÃÃes referentes a encaminhar: cardiologista (18), odontologista (12), nutricionista (10), oftalmologista (8) e nefrologista (7), e orientar: para diminuir peso (9), dieta (8), orientaÃÃes (5); manter: cuidados (5). Observou-se que a intervenÃÃo mais registrada foi verificaÃÃo da pressÃo arterial (257), no entanto, mesmo essa sendo caracterizada como uma aÃÃo especÃfica e imprescindÃvel na consulta de enfermagem ao portador de hipertensÃo arterial, nÃo se fez presente em todas as consultas. Esse fato parece indicar a ocorrÃncia de sub-registros pelos enfermeiros, o que representa prejuÃzo para a avaliaÃÃo sistemÃtica do cliente e acompanhamento da eficÃcia de sua terapÃutica. Conforme se conclui, a anÃlise de registros de consultas de enfermagem possibilitou identificar intervenÃÃes e aÃÃes de enfermagem paralelas com as intervenÃÃes relacionadas na CIPE 1. No entanto, sub-registros podem estar ocorrendo, fazendo com que o quantitativo de intervenÃÃes seja inferior ao que poderia se esperar em face da especificidade das consultas analisadas. / The performance of the nurse in the consultations to carriers of hypertension, carrying through specific actions and systemize interventions, has increasing importance because, not rare, the customer lacks of interventions that run away from the ability of one alone professional. It was had as objective to identify registered interventions of nursing in handbooks of taken care of carriers of hypertension in a reference service; to detect the frequency of the register of the interventions; to analyze, on the basis of the Plan of Reorganization of the attention to the Hypertension and Diabetes Mellitus (2001) and in the Brazilian Lines of direction of Hypertension (2006), the interventions with a frequency equal or bigger the five times in the registers; e to mapear the found interventions, according to International Classification for Nursing Pratice, version 1.0. It was carried through in the city of Fortaleza, in a unit of health of reference in hypertension and diabetes mellitus, for the state CearÃ. Universe consisting of 3.606 registered in cadastre handbooks of July of 2003 the July of 2005, in a total of 704 handbooks with register of the diagnosis of hypertension. Amongst these, 175 handbooks had taken care of to the inclusion criteria: to be handbook of carrying patient of the diagnosis of arterial or primary hypertension, without other disease, as neoplasias, hematology, neuro-psychiatric, bones, metabolic and renals illnesses; to be registered in cadastre, and in validity since July of 2003; independent of sex and age and, to have register of, at least, a nursing consultation. The data had been collected in handbooks for the analysis of the registers of the carried through consultations of nursing of December of 2005 the February of 2006. A form was used that had as axle the questions necessary to reach the considered objectives. In 175 handbooks, it had register of 259 consultations of nursing (average: 1,48). In all had registers of interventions, in a total of 10 actions of nursing and 972 registers of interventions, with a average of 3,7 interventions for consultation. The actions presented had been: to verify (819), to guide (71), to direct (65), to teach (7), to keep (5), to stimulate (1), to acquire knowledge (1), to prevent (1), to request (1) and to watch (1). In the action to verify interventions had been distinguished that had occurred with a frequency equal or bigger the five times: blood pressure (257), weight (217), glicemy (212), height (86); following itself for the referring interventions to direct: cardiologist (18), dentist (12), nutrition (10), ophthalmologist (8) and nephrologist (7) and to guide: to diminish weight (9), diet (8), orientation (5); to keep: cares (5). It was observed that the registered intervention more registered was verification of the arterial pressure (257), however it being characterized as a specific action and essential in the consultation of nursing to the carrier of hypertension, it was not presented in all consultations. This fact seems to indicate, the occurrence of sub-registers for the nurses, what it represents damage for the systematic evaluation of the customer and accompaniment of the effectiveness of its therapeutical one. One concludes that the analysis of registers of nursing consultations made possible to identify to interventions and action of nursing parallel with the interventions related in ICNP 1. However, sub-registers can be occurring, making with that the quantitative one of interventions is inferior to that face to the specific of the analyzed consultations could expect.

Class of 2015 Abstract / Objectives: The specific aim of the study was to examine the effects of a 30-minute educational intervention, developed and delivered by student pharmacists, on knowledge of hypertension and its management among community-dwelling older adults and their caregivers. The study also aimed to examine the helpfulness of the program and readiness of the participants to adopt healthier lifestyle practices afterward. Methods: This was a pre- and post-interventional study. At senior centers around the Phoenix metropolitan area, community-dwelling older adults (ages 60 or older) and family members or caregivers (ages 18 or older) were recruited to participate. Participants completed knowledge-based questionnaires prior to and after the educational program. The mean number of correct responses was calculated for pre- and post-program questionnaires, then compared using paired t-test. Results: A total of 77 individuals participated in the program with mean age of 72 and 67% female. The mean number of correct responses calculated for survey before the educational program was 3.03 and 5.46 for survey after the program, which was significantly different (p <0.01). 85% of participants reported the program to be helpful, and 84% participants were willing to adopt healthier lifestyle after attending the program. Conclusions: An intervention tailored to community-dwelling older adults, developed and delivered by student pharmacists, was found to improve awareness of hypertension and generated willingness to adopt healthier lifestyle among the participants.

Does having a positive family history of essential hypertension predispose one to greater cardiovascular reactivity? Could reactivity be assessed with stress tasks that have greater external validity than traditional laboratory stressors? To answer these questions? 2b subjects with parental history of essential hypertension and 3b subjects without) were induced to converse with an experimenter on (a) a neutral topic (the weather)? and (b) an affective topic (a frustrating person or event). The topics were selected from a Iist of 2b because they had been rated by undergraduates as being the least and most arousing topics to talk about with a stranger in an experimental situation. The ratings yielded no interactions of sex of experimenter with sex of the subject. Subjects also performed a mental arithmetic task which is a standard laboratory stressor. The order of task presentation was randomly assigned within groups but matched across groups and sex to control sequence effects. For each subject? a 15-minute base I ine period was al lowed before each task. Readings of blood pressure? heart rate and rate of respiration were made at minute one? three? and five of each task phase. Each conversation task consisted of five minutes of talking followed by Iistening for five minutes to the experimenter. The tasks were separated by five-minute intervals to allow return to baseline levels. Results indicated that compared to individuals without parental history of hyper tension? individuals with parental history displayed higher levels of blood pressure (but not heart rate and rate of respiration) whether talking or listening. When peak values were considered; positive parental history subjects showed greater reactivity to the affective topic on diastolic blood pressure. The results also indicated that the three kinds of stressors yielded different levels of physiological responses with the math task and talk phase of the affect task yielding higher levels of blood pressure and heart rate than talk about the weather. The difference between the math and affective tasks was not significant on systolic blood pressure? but math yielded higher responses on heart rate and lower responses on diastolic blood pressure than talking about a frustrating event or person. These results suggest that a more generalizabIe stress stimulus such as an affect-laden conversation? can be reasonably standardized across subjects and elicits an aIpha-adrenergic vaso-constrictive response? a response more readily given by individuals with positive parental history than individuals without. The results also suggest that individuals with positive parental history of hypertension have higher blood pressure levels than individuals without. With respect to the similarity of the findings of this study? with those of other studies which have used older populations? it is proposed that these results are generalizable to older populations and provide evidence that a positive family history of essential hypertension may be considered a risk factor for later cardiovascular disease. / Arts, Faculty of / Psychology, Department of / Graduate

No description available.

No description available.

No description available.

Myh9 is a gene that encodes for non-muscle myosin IIA (NM-IIA), an actin cytoskeleton component and protein involved in cell movement and adhesion in most cells, including podocytes. Autosomal dominant mutations in NM-IIA have been associated with focal segmental glomerular sclerosis (FSGS) in patients with the mutation. Furthermore, a strong association has been discovered between genetic variation in the Myh9 region on chromosome 22, and the increased risk of chronic kidney disease in African Americans. Later studies by Johnstone et al. using podocyte specific, Myh9 KO in mice showed that knocking out this gene alone was not enough to cause proteinuria or glomerular sclerosis. However, in our own laboratory we have found that when these same mice are exposed to models of glomerular hypertension, glomerular damage is promoted. This damage was preceded by evidence of podocyte loss in urine and tissue. Podocyte loss is a hallmark of kidney disease, and while it is known to occur in vivo, the mechanisms behind this phenomenon are unknown. It is believed that increase in glomerular capillary blood pressure is likely to be a strong contributing factor. Based on these findings, we hypothesized that the mechanical strain in the form of stretch, occurring during hypertension, may act as a second hit to Myh9 ablation in podocytes, causing changes in podocytes ability to adhere to the glomerular basement membrane (GBM), ultimately leading to the pathology seen in patients. To test this, we knocked down Myh9 in immortalized mouse podocytes cultured on flexible silicon membranes and exposed them to mechanical stretch for 24hrs. Cell adhesion was evaluated via cell attachment assays. Cell morphology and focal adhesions (FA) were examined using immunofluorescence and quantified using imageJ. Our results showed a significant decrease in transduced cells attached to the membrane after stretch, as well as an increase in FA size and number in cells that underwent stretch, except in the Myh9 knockdown. Cells with Myh9 knockdown also showed marked increase in area, with a decrease in FA size and number after exposure to stretch. These results support our hypothesis that Myh9 mutations may be a contributing factor to podocyte loss in patients with hypertension and chronic kidney disease.