by Yuk-Tong Lee. / "September 2001." / Thesis (M.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 255-288). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

Introduction: Hepatorenal syndrome (HRS) is a common complication of advanced cirrhosis with a high mortality rate and limited treatment options. Central to its pathogenesis is severe, but potentially reversible, renal vasoconstriction leading to functional renal failure. Current pharmacological treatment using splanchnic vasoconstrictors is suboptimal and prognosis without liver transplantation is dismal. The peptide hormone relaxin (RLN) mediates haemodynamic adaptations to pregnancy including increased renal blood flow (RBF) and glomerular filtration rate (GFR). I hypothesised that exogenous RLN could be used therapeutically to improve RBF and renal function in the context of experimental cirrhosis and HRS. Methods: To address this I generated pathologically distinct rat models of liver cirrhosis with features of human HRS including renal vasoconstriction and renal failure. Compensated cirrhosis was induced in male rats by 16 weeks of i.p. carbon tetrachloride (CCl4) and decompensated cirrhosis by bile duct ligation (BDL). I studied the effects of acute i.v. or sustained (72 hr) s.c. infusion of RLN compared with vehicle on systemic haemodynamics, RBF, GFR and kidney histology. I used blood oxygen dependent-magnetic resonance imaging (BOLD-MRI) to detect changes in kidney parenchymal oxygenation and Doppler ultrasound to monitor changes in RBF (velocity time integral, VTI) and renal arterial resistance (resistive index, RI). Hepatic and renal expression of the relaxin receptor RXFP1 was determined by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Vascular functional responses in isolated renal arteries were assessed by wire myography. Relaxin mediated changes in key vaso-regulatory signalling pathways in the kidney and renal vessels were analysed by qPCR, IHC and ELISA. Results: I showed using in vitro myography that the pathophysiological mechanism that underlies renal vasoconstriction in experimental cirrhosis models is an impairment of endothelium-dependent vasodilatation. Selective targeting of renal vasoconstriction using relaxin improved renal blood flow, tissue oxygenation, and normalized glomerular filtration rate in both compensated and decompensated rat cirrhosis. Furthermore, relaxin treatment restored endothelium-dependent vasodilation in isolated renal vessels from CCl4 cirrhotic rats. Relaxin-induced effects on renal blood flow and glomerular filtration rate were mediated though activation of the AKT/eNOS/nitric oxide signalling pathway in kidney, though systemic nitric oxide levels were unaffected. Crucially for human translation, relaxin did not reduce mean arterial blood pressure even in advanced cirrhosis. Conclusion: My findings identify relaxin as the first potential targeted treatment reversing the vascular dysfunction which causes HRS and directly improving renal function in HRS. Clinical translation in carefully selected populations is warranted.

Introdução: o controle da hipertensão é pouco satisfatório e medidas devem ser implementadas para aumentá-lo. Realizou-se um estudo para avaliar o controle da hipertensão após intervenções educativas junto a hipertensos e equipe de enfermagem em duas unidades básicas de saúde. Casuística e Métodos: foram estudados com 55 membros da equipe de enfermagem e 290 hipertensos, separados em dois grupos: grupo I, que recebeu intervenções educativas e grupo II que seguiu a rotina normal da unidade. Os dados biossocial-econômicos, as avaliações antropométricas e medida da pressão arterial foram coletados. Foram realizadas entrevista e três medidas de pressão arterial com aparelho automático validado, manguito adequado e na posição sentada. A adesão ao tratamento foi avaliada pela presença de fatores dificultadores e Teste de Morisky e Green. Para ingestão de bebida alcoólica usou-se o Alcohol Use Disorders Identification - AUDIT, presença de transtornos mentais comuns pelo Self Report Questionnaire - SRQ-20 e apoio social pela escala de Apoio Social. As análises univariada e multivariada foram realizadas com nível de significância de p<0,05. Os membros da equipe de enfermagem foram avaliados no conhecimento sobre hipertensão antes e após processo educativo. Resultados: o conhecimento dos enfermeiros, técnicos e auxiliares de enfermagem elevou-se após processo educativo (84,6±12,0% vs 92,7±15,0%, p<0,05) e para agentes comunitários de saúde não houve mudança significante (80,8±12,2% vs 83,5±24,0%). Os hipertensos estudados tinham idade maior que 60 anos (54,8%), sexo feminino (62,1%), etnia branca (54,5%), primeiro grau (56,9%), autônomos (42,5%) e renda de um a três salários mínimos (52,7%). A maioria não referiu tabagismo (60,6%) nem etilismo (64,3%). A adesão ao tratamento avaliada pelo Teste Morisky e Green mostrou que 64,75% dos hipertensos do grupo I e 72,7% do grupo II não eram aderentes ao tratamento. Na avaliação pelos fatores que interferem ao tratamento, 77,3% do grupo I e 67,8% para o grupo II eram aderentes ao tratamento. Houve presença de transtornos mentais comuns em 40,0% dos hipertensos do grupo I e 43% do grupo II. A Escala de apoio Social revelou valores das médias do total da escala, bem como de seus diferentes domínios bem próximas entre os dois grupos de hipertensos estudados e alto valor de apoio social (76,1±17,9 grupo I e 76,9±14,0 grupo II). O controle da pressão arterial antes e após intervenção educativa foi, respectivamente, para o grupo I: 46,5% e 63,2% (p<0,05). e grupo II: 33,6% e 56,8% (p<0,05) e o controle foi mais elevado nos hipertensos do grupo I. Com relação ao controle da pressão, houve diferença estatisticamente significante (p<0,05) nas variáveis: sexo, predomínio de mulheres mais controladas que homens (66,7% vs 33,3%), etnia, brancos mais controlados que não brancos (62,3% vs 37,7%), os que tinham escolaridade de ensino fundamental/ médio mais controlados que os analfabetos (64,0% vs 47,1%) e nunca beberam (70,4% vs 28,6%). Os que possuíam renda < três salários apresentaram-se menos controlados (73,5% vs 26,5%) e os que não praticavam atividades físicas regularmente (75,0 vs 25,0%).. A análise de regressão logística indicou associação do controle da pressão para (OR Odds ratio, IC intervalo de confiança a 95%): 1) etnia, (p=0,030, OR=1,939, IC 1,064-3,533), 2) renda familiar (p=0,020, OR=0,447, IC 0,227-0,881) e 3) ingestão de bebida alcoólica (p=0,001, OR=3,206, IC 1,573-6,536). Conclusão: O processo educativo influenciou no maior controle da pressão dos pacientes e melhorou o conhecimento dos profissionais da equipe de enfermagem / Introduction: The control of the hypertension is little satisfactory and measures should be implemented to increase it. It took place study to evaluate the control of the hypertension close to after educational interventions hypertensions and nursing team in two basic units of health. Populations and Methods: They were studied with 55 members of the nursing team and 290 hypertensive patients, separate in two groups: group I, that received educational interventions and group II that it followed the normal routine of the unit. Bio-partner-economical data were collected; evaluations anthropometrics and measure of the blood pressure. Made interview and three blood pressure measures with validated automatic device, appropriate cuff and in a sitting position . The compliance to the treatment was evaluated by the presence of factors difficults and Morisky and Green Test. For ingestion of alcoholic drink Alcohol was used Uses Disorders Identification - AUDIT, presence of common mental upset for Self Report Questionnaire - SRQ-20 and social support for the scale of Social Support. It took place analysis univaried and multivariate with level of significance of p <0.05. The members of the nursing team were before appraised in the knowledge on hypertension and after educational process. Results: The nurses\' knowledge, technicians and nursing auxiliaries rose after educational process (84.6±12.0% vs. 92.7±15.0%, p <0.05) and for community agents of health there was not significant change (80.8±12.2% vs. 835±24.0%). The studied hypertensive patients had larger age than 60 years (54.8%), female (62.1%), white ethnic (54.5%), first degree (56.9%), autonomous (42.5%) and income from 1 to 3 minimum wages (52.7%). most didn\'t refer tobacco (60.6%) and neither alcohol intake (64.3%). The compliance to the treatment evaluated by the Morisky and Green Test showed that 64.75% of the hypertensive of the group I and 72.7% of the group II were not adherent to the treatment. In the evaluation for the factors that interfere to the treatment 77.3% of the group I and 67.8% for of the group II they were adherent to the treatment. There was presence of common mental upset in 40.0% of the hypertensions of the group I and 43% of the group II. The Scale of Social support revealed values of the averages of the total of the scale, as well as of their different domains very close between the two groups of studied hypertensive patients and high value of social support (76.1±17.9 group I and 76.9±14.0 group II). The control of the blood pressure before and after educational intervention it was, respectively, for the group I: 46.5% and 63.2% (p <0.05). and group II: 33.6% and 56.8% (p <0.05) and the control was higher for the hypertensive patients of the group I. In a relation to the control of the pressure, there was difference significant statistically (p <0,05) in the variables: sex, women\'s prevalence more controlled that men (66.7% vs. 33.3%), ethnic, white more controlled that no white (62.3% vs. 37.7%), the ones that had education of teaching high school and junior high school more controlled that the illiterates (64.0% vs. 47.1%) and they never drank (70.4% vs. 28.6%). The ones that possessed income <3 wages came less controlled (73.5% vs. 26.5%) and the ones that didn\'t practice physical activities regularly (75.0 vs. 25.0%). The analysis of regression logistics indicated association of the control of the pressure for (OR Odds ratio, CI confidence interval to 95%): 1) ethnic, (p=0.030, OR=1.939, CI 1.064-3.533), 2) family income (p=0.020, OR=0.447, CI 0.227-0.881) and 3) ingestion of alcoholic drink (p=0.001, OR=3.206, CI 1.573-6.536). Conclusion: The educational process influenced in the largest control of the patients\' pressure and it improved the professionals\' of the nursing team knowledge

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Secreted by adipose tissue, leptin acts as a signal of energy reserve status, and acts in the brain as a negative feedback mechanism to suppress food intake and increase energy expenditure, the net effect of which is maintenance of energy homeostasis. In addition to its role as a satiety factor, leptin has widespread autonomic effects, increasing sympathetic tone to a variety of tissues, including those involved in arterial pressure regulation. Thus, leptin has been implicated as a critical link between obesity and hypertension. However, the specific mechanisms whereby leptin elicits its diverse effects are not fully understood. This is further complicated by the many sites of leptin action within the brain, as well as its diverse intracellular effects. Here, we investigate the possibility that distinct aspects of leptin function are controlled by different neuronal populations and/or molecular signaling cascades. Specifically, we identify unique roles for leptin action on POMC and AgRP neurons in differentially mediating the regional sympathetic effects of leptin. Furthermore, we show that leptin action via mTORC1 is required for the cardiovascular sympathetic but not the metabolic effects. Together, these findings point to complex neuroanatomical and molecular differences in the mechanisms underlying leptin’s effects on different physiological processes, with important implications for future research into obesity-associated hypertension.

Hypertension is a complex multifactorial pathology that is a major risk factor for the development of cardiovascular disease, stroke, and end stage renal disease. In the United States, hypertension affects over 1 in 3 adults and comprises an annual cost of over $58 billion in the healthcare industry. While remarkable strides in the diagnosis and treatment of hypertension have been made since the pathology was first treated in the 1960s, a remarkable 13% of patients with elevated blood pressures are classified as resistant hypertensive, where blood pressure remains uncontrolled while on three or more classes of anti-hypertensive drugs. This treatment gap suggests that researchers need to develop and utilize translational models that recapitulate the pathologies seen in patient populations. Non-human primates (NHP) are highly similar to humans in terms of physiology, circadian rhythmicity, behavior, and gene sequence and structure. Development of NHP models that spontaneously develop pathologies, like spontaneous hypertension, provide novel and vital tools to studying disease. Overall, this dissertation is a comparative analysis of the mechanisms that drive the development of spontaneous hypertension in Chlorocebus aethiops sabaeus, an Old World non-human primate, and known mediators of essential hypertension in human populations. Chapter 2 presents how hypertensive (HT) African Green Monkeys (AGMs) are older, with elevated heart rates, increased renal vascular wall/lumen ratios, and altered glomerular morphologies compared to normotensive (NT) controls. Chapter 3 describes metabolic studies performed in a large cohort of animals that identified elevated proteinuria and ion excretion in HT AGMs compared to NT animals. Chapter 4 focuses on the contribution of sympathetic nervous system to the development of hypertension in this animal model and describes the significant left ventricular hypertrophy and elevation of adrenergic receptor mRNA in HT AGMs. Chapter 5 examines how age affects hypertension and renal function in the NT and HT AGMs. Together these data provide a foundational basis for the development of spontaneous hypertension in the AGM and provide a novel translational model for the study of cardiovascular disease.

Hypertension is a serious medical condition. Although men and women of all racial groups in the US suffer from high blood pressure, black women have the highest rates of hypertension. For instance, the age-adjusted prevalence of hypertension among black women ages 20 and over is 44.3, compared to 28.1 among white women, 40.5 among black men, and 31.1 among white men. Past research has focused on SES and behavioral factors as potential explanations for blood pressure disparities between black and white women. But, even after controlling for such factors, considerable disparities remain. The goal of this research is to examine cultural and social factors that have been shown to increase blood pressure. Specifically, I examine social support, psychosocial characteristics, and contextual factors associated with race/ethnicity and hypertension, in hopes of explaining some of the disparities in high blood pressure between black and white women. iii Using data from Waves I, III, and IV of the National Longitudinal Study of Adolescent Health (Add Health), I estimated a sequence of multinomial logistic regression models predicting prehypertension and hypertension in young adulthood. Cross-sectional models show that racial disparities in hypertension remain after controlling for social support, psychosocial characteristics, and contextual factors. In fact, the only covariate that substantially reduced the racial disparity in hypertension was body mass index (BMI), a fairly reliable measure of body fatness for most people. I also estimated a set of multinomial logistic regression models predicting odds of prehypertension and hypertension by adolescent and cumulative social support, as well as psychosocial, contextual, and behavioral factors. These models were included to determine if early life and/or cumulative factors and conditions would help explain racial blood pressure disparities not explained by adulthood factors. Findings show that none of the early life or cumulative social support, psychosocial, contextual, or behavioral factors helped to explain racial differences in prehypertension or hypertension. Even after controlling for these factors, black women are still 1.18 times more likely than white women to have prehypertension and over two times more likely to suffer hypertension. Indeed, my findings indicate that, of the factors included in all these models, only race, age, and BMI were significant predictors of blood pressure. Also, BMI was the only factor to explain some of the disparities between black and white women. These results are similar to other studies that have examined racial health disparities, suggesting that simply being a black woman in US society may be unhealthy. The health effects of racism, discrimination, and other sources of stress faced disproportionately by black women are not easily measured by social science research, which is possibly why racial disparities in blood pressure have yet to be explained. Future research should also explore possible epigenetic effects introduced by the health conditions experienced by previous generations, as well as the influence of prenatal and early life environments.

In the present study, we investigated the pathophysiological mechanisms of the hemodynamic alteration in diabetes. Glomerular hyperfiltration occurs in the early stage of diabetes mellitus and has been recognized to promote the pathogenesis of diabetic nephropathy. We determine the role of TGF response and the vascular tone of Af-Art in diabetic hyperfiltration and we found that 1) tubular high glucose directly activates NOS1 and increases NO generation in the macula densa, which inhibits TGF response and increases GFR; 2) high glucose dilates renal Af-Art through GLUT1 and mediated by NOS3-derived NO generation; 3) in diabetes, blunted TGF mediated by NOS1 in the macula densa promotes glomerular hyperfiltration. The prevalence of hypertension is much higher in diabetic subjects than non-diabetic population. We studied the potential mechanisms of blood pressure regulation in diabetes, including TGF response and renal afferent arteriolar response to vasoconstrictors, and we found that 1) inadequate NOS1 in the macula densa enhances TGF, which restricts glomerular hyperfiltration and induces hypertension in diabetes; 2) hemodynamic responses to ANG II is increased in diabetes, which is associated with increased expression and activity of AT1 receptors in the Af-Art; 3) Ang II upregulates the expression and activity of Nox2 and Nox4 in the macula densa, which enhances TGF response.

No description available.

Background The incidence of hypertension is increasing in developing countries such as Thailand (Chaiteerapan et al 1997; Ministry of Public Health 2001; National Library of Thailand Cataloguing in Publication Data 2001) as a result of sociological, political and economic changes. These changes are producing enormous alterations in people�s lifestyles, following similar trends in western countries (National Economic and Social Development Board 1997). Negative changes in food consumption, alcohol consumption, level of physical activity, smoking, stress and tension have led to an increase in chronic health problems for Thai people (National Economic and Social Development Board 1997). Age, gender, ethnicity, genetic background, family health history and hyperlipidaemia are likely to influence hypertension (Kaplan, Lieberman & Neal 2002; Mancia et al 2002; Manger & Gifford 2001; National Heart Foundation of Australia 2003). It has been found that health care professionals and patients with chronic disease have increased their use of complementary therapies to help relieve uncomfortable symptoms and suffering (Long, Huntley & Ernst 2001). Foot reflexology is a well known complementary therapy which claims to help the body achieve homeostasis (Byers 2001; Dougans 2002). It is believed that pressing specific areas on the feet related to specific glands or organs of the body can help these glands and organs to function at their peak, allowing the body to heal itself (Byers 2001; Dougans 2002). The principle difference between massage or touch and foot reflexology is that foot reflexology provides not only the relaxation effect obtained from massage or touch is said to also improve body�s immunity contributing to healing process (Byers 2001;Dougans 2002). Foot reflexology has been scientifically researched in many studies to explore the claimed benefits (Bishop 2003; Kohara et al 2004; Oleson & Flocco 1993; Siev-Ner et al 2003; Yang 2005). Some studies have supported its ability to reduce anxiety and pain (Gambles, Crooke & Wilkinson 2002; Launso, Brendstrup & Arnberg 1999; Stephenson, Dalton & Carlson 2003; Stephenson, Weinrich & Tavakoli 2000). However, there has been little scientific evidence to support the claim that foot reflexology can reduce blood pressure and serum lipids, and can improve the quality of life in patients with hypertension (Hodgson 2000; Milligan et al 2002; Park & Cho 2004). The purpose of this study was to begin to fill this gap by investigating the influence of foot reflexology on blood pressure, serum lipids and quality of life. Aim The aim of this study was to investigate the effect of foot reflexology on reducing blood pressure in patients with hypertension. To this end, patients receiving reflexology were compared with patients receiving a light foot massage, thus controlling for any effects contributed by massage or touch alone. Null hypotheses 1. There is no difference in mean blood pressure level between the foot reflexology group and the light foot massage group at the end of four weeks of treatment. 2. There is no difference in mean low density lipoprotein (LDL) cholesterol and triglyceride levels between the foot reflexology group and the light foot massage group at the end of four weeks of treatment.3. There is no difference in mean quality of life scores between the foot reflexology group and the light foot massage group at the end of four weeks of treatment. Sample A sample size of 128 was required to yield a power of 80%, if the difference in mean diastolic blood pressure between the two groups was 5 mmHg. One hundred twenty eight patients with hypertension who attended the hypertensive clinic in the medical outpatients department of Phramongkutklao Hospital, Bangkok, Thailand were enrolled and participated in the study. Methods Data collection This study used a randomized controlled trial design. Participants were randomly allocated into one of two groups � 64 participants in the foot reflexology group (intervention) and 64 in the light foot massage group (control). Data collection took place over 4� months between 26 July and 9 December 2004. Ethics approval was obtained from both the university and hospital ethics committees. Prior to randomization, participants were asked to complete a demographic data questionnaire and the World Health Organization Quality of Life-BREF (WHOQOLBREF) (World Health Organization 1996) questionnaire. Blood was drawn to test LDL cholesterol and triglyceride levels. Using an intervention protocol based on previous literature (Byers 2001), participants in the foot reflexology group received their usual medical treatment and a 50-minute foot reflexology treatment twice a week for four weeks. Participants in the light foot massage group received their usualmedical treatment and a 30-minute light foot massage session without pressure on specific reflexology areas twice a week for four weeks. Blood pressure was recorded before and after each treatment. At the end of the study, participants were asked to complete the WHOQOL-BREF (World Health Organization 1996) again and blood was once more drawn to test LDL cholesterol and triglyceride levels. Data analysis An independent samples t-test followed by analysis of covariance was used to test for difference in mean diastolic blood pressure between treatment groups both unadjusted and adjusted for baseline values respectively. Descriptive statistics were used to present the demographic data. Results Demographic data Control and intervention groups were similar in gender, age, educational background, economic factors, lifestyle characteristics, co-morbidities and medical treatments. Demographic data which were substantially different between groups were marital status, the length of time experiencing hypertension and the length of time having treatment for hypertension. The study showed that fewer participants in the foot reflexology group (57.8%) were married than in the light foot massage group (70.3%). The foot reflexology group also had a higher rate (32.8%) of �divorced/separated/widowed� compared with the light foot massage group (20.3%). Participants in the light foot massage group had almost nine times the number of participants who had had hypertension for more than 15 years, and almost eight times the number of participants who had been having treatment for hypertension for more than 15 years, compared with those in the foot reflexology group. Outcome variables For both the unadjusted and adjusted analyses, there was no statistically significant difference between treatment groups post-intervention. Conclusions The results from this study did not support the claim that foot reflexology can decrease blood pressure, LDL cholesterol and triglyceride levels. Similarly, there was no evidence that it could improve the quality of life in patients with hypertension.