Enlargement of adipocytes in obesity leads to alteration in adipokine production and these changes are linked to the development of obesity-related cardiovascular diseases. Adipokines specifically associated with obesity-related hypertension include angiotensinogen and adiponectin. Conjugated linoleic acid (CLA) has been reported to reduce blood pressure in obese insulin-resistant rats, but its mechanism of action has not been identified. The objective of this study was to determine whether CLA’s ability to improve obesity-related hypertension involves reducing adipocyte size and altering adipokine production. Fa/fa Zucker rats (6 or 16 week old) were fed diets containing CLA isomers for 8 weeks. The trans(t)10,cis(c)12-CLA isomer reduced adipocyte size in both younger and older rats. Despite beneficial changes in cell size of rats fed the t10,c12-CLA isomer, there were no changes in the renin-angiotensin system or pro-inflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 or the anti-inflammatory cytokine IL-10. In contrast, the t10,c12-CLA isomer increased adiponectin levels both in the circulation and in adipose tissue. This was associated with increased phosphorylation of endothelial nitric oxide synthase (eNOS) in adipose tissue and aorta. Direct treatment of CLA isomers in cultured endothelial cells did not increase eNOS phosphorylation but increases were observed with adiponectin treatment. In vivo, infusion with adiponectin increased eNOS phosphorylation in adipose of fa/fa Zucker rats in parallel with improvements in blood pressure. Similarly, when circulating levels of adiponectin increased in rats fed the t10,c12-CLA isomer diet, blood pressure was also attenuated. In younger rats, both the t10-c12 and c9,t11-CLA isomers were significantly different from the control group at week 8, however, only the t10,c12-CLA isomer was comparable to the commonly used anti-hypertensive medication captopril. In conclusion, the beneficial effects of the t10,c12-CLA isomer on blood pressure may in part be due to its ability to reduce the number of large adipocytes in vivo, thus increasing the production of adiponectin which subsequently activates vascular eNOS.

The thesis offers the following contributions to the epidemiology of hypertension in Canada: 1.The first manuscript uses cross-sectional data from the 2007-2009 Canadian Health Measures Survey (CHMS) to compare the prevalence of controlled hypertension between people with and without diabetes. Of the 74% of Canadians with diabetes who had hypertension, 56% (95% CI: 45%-66%) had controlled blood pressure compared to 64% (95% CI: 58%-69%) of Canadians without diabetes. Among people taking medication, individuals with diabetes were less likely to have controlled hypertension (ORadjusted: 0.3; 95% CI: 0.2-0.6). 2.The objective of the second manuscript was to determine, among Canadians with hypertension, whether individuals with diabetes were less likely than those without to recall health professional advice for healthy behaviours and whether receipt of such advice influences behaviour, using cross-sectional data from the 2009 Survey on Living with Chronic Diseases in Canada (SLCDC). Canadians with diabetes were more likely than those without to recall advice to control/lose weight (81% vs. 66%), exercise (79% vs. 68%), limit alcohol (78% vs. 55%) and modify diet (70% vs. 61%) but not limit salt (65% vs. 64%). Both groups were equally likely to report following advice, with receipt of advice positively associated with engagement in healthy behaviours. 3. The third manuscript describes knowledge of blood pressure targets in Canadians with hypertension using cross-sectional data from the 2009 SLCDC. Knowledge of blood pressure targets was low, with 28% and 32% of Canadians with and without diabetes reporting having discussed a blood pressure target and reporting a target in line with clinical practice guidelines. 4.The fourth manuscript validates an existing self-reported blood pressure control question in a sample of 161 patients with hypertension in Kingston. In people with and without diabetes, the question had sensitivities of 83% ± 11% and 78% ± 10% and specificities of 30% ±19% and 58% ± 21%, respectively. 5.The final manuscript tests a method designed to account for misclassification in epidemiologic studies, using data from the CHMS. The method was found to perform inconsistently in multivariate contexts and introduced bias when minor differential misclassification was ignored. / Thesis (Ph.D, Community Health & Epidemiology) -- Queen's University, 2013-11-14 09:55:12.161

Background: In the context of transitional Vietnam, hypertension has been shown to be one of the ten leading causes of morbidity and mortality in hospitals. However, population-based data on hypertension are to a large extent lacking. This thesis aims to characterise the current epidemiology of hypertension in the adult Vietnamese population and provide preliminary evidence for developing effective community-based hypertension management programmes nationwide. Methods: The study was conducted during 2002-2010. It includes two national surveys of the adult population aged 25 years and older, randomly selected in eight provinces in different regions of Vietnam, as well as a community-based programme on hypertension management in two communes of Bavi district. The survey on hypertension and associated risk factors, which included 9,832 adults, applied the WHO STEP-wise approach. The survey on hypertension-related knowledge and health seeking behaviour included 31,720 adults, using a structured questionnaire. For the community-based study, three-year follow-up data on 860 hypertensives was used to assess the effectiveness of the hypertension control model. Main findings: Hypertension prevalence was high (overall 25.1%, 28.3% in men and 23.1% in women). The proportions of hypertensives aware, treated and controlled were unacceptably low (48.4%, 29.6% and 10.7% respectively). Most Vietnamese adults (82.4%) had good knowledge about high blood pressure. People received their information on hypertension from mass media (newspapers, radio, and especially television). Most people would choose a commune health station (75%) if seeking health care for hypertension. The programme on hypertension control was able to run independently at the commune health station. Severity of hypertension and effectiveness of treatment were the main factors influencing people’s adherence to the programme. The hypertension control programme successfully reduced blood pressure (systolic blood pressure: -2.2 mmHg in men and -7.8 mmHg in women; diastolic blood pressure: -4.3 mmHg in men and -6.8 mmHg in women), the estimated CVD 10-year risk (-2.5% in women), and increased the proportions of treatment (22% in men and 13.6% in women) and control (11% in men and 17.3% in women) among hypertensive people. Suggestions for hypertension control: (1) Address the general population by developing community interventions, particularly salt reduction; (2) Provide interventions to individuals at high risk of a CVD event, including multi-drug treatment within patient-centred primary health care. (3) Set up a hypertension care network based in the existing health care system; (4) Improve and strengthen capacity and skills of medical staff in cardiac care, particularly staff at primary care level.

No description available.

The physiological responses of hypertensive subjects to a single bout of exercise in a hot environment have been investigated. It was the purpose of this study to compare the effect of successive days of exercise in the heat on borderline hypertensive and normotensive individuals, with particular interest being paid to the positive relationship that exists between plasma volume and blood pressure. Eight hypertensive subjects (HT) and 8 normotensive controls (NT) performed a standardized work task, (walking for 60 minutes at 3.5 mph on a 5% grade), in dry heat, (40C, 257. RH), on 7 successive days. Working capacity and acclimatization were compared during two, 90 minute heat tolerance tests (HTT), one prior to, and the other following the acclimation period.Both groups demonstrated a similar degree of heat acclimation, as reflected in significantly lower HTT2 core temperatures, (P< 0.05), and heart rates, (p< 0.01). Plasma volume expansion over the 9 days was also equal for both groups (+77.), but appeared to have no effect on their resting or exercising blood pressures. No differences were observed in the ability of either group to complete the work task, although the HT group exercised at a significantly higher percentage of their maximal oxygen uptake, (p< 0.05), than the NTs.These results indicate that no abbreviation in working capacity is experienced by borderline HT'% during exercise in the heat as a consequence of their high blood pressure. The anticipated elevation in blood pressure as a result of an expansion i n plasma volume did not occur. Consequently, these individuals show the same positive acclimation to exercise in the heat as their NT counterparts. / School of Physical Education

Pulmonary arterial hypertension (PAH) is a lethal disease characterized by excessive proliferation of pulmonary vascular cells, such as endothelial cells (ECs). Hereditary (H) PAH is mainly caused by ―loss-of-function‖ mutations in the gene coding for the bone morphogenetic protein type II receptor (BMPR2). However, the mechanisms by which these mutations cause PAH remain unclear. The hypothesis of this thesis was that BMPR2 mutations produce an imbalance in EC protein expression and/or activity that is integrally related to the development of abnormalities in lung vascular function and structure in HPAH. Patient-specific blood-outgrowth endothelial cells (BOECs) expanded ex vivo from peripheral blood mononuclear cells from patients with HPAH and healthy subjects were used to examine the consequences of BMPR2 mutations on the BOEC protein expression profile as well as on their functionality. Functional analyses of the BOECs revealed that HPAH-derived BOECs are more susceptible to apoptosis and more proliferative compared with healthy controls. Protein isolates of BOECs from patients with HPAH and from healthy subjects were subjected to 2-D gel electrophoresis and stained for total proteins and phosphoproteins, and to a quantitative computerassisted analysis. Differentially regulated proteins were identified by mass spectrometry (LC-MS/MS). Of the 416 total proteins detected under basal conditions, 11 were significantly downregulated in HPAH-derived BOECs and 11, including the translationally controlled tumor protein (TCTP), were upregulated. TCTP has previously been shown to be involved in systemic arteriolar remodeling, inflammation and growth. Therefore, the potential role of TCTP in PAH was studied in vivo in the SU5416 rat model of severe angioproliferative PAH. Immunofluorescence staining revealed high expression of TCTP in arteriolar ECs of PAH lungs tightly localized to proliferating cells within occlusive intimal lesions; whereas, only minimal TCTP expression was seen in vascular ECs of normal lungs. Similarly, abundant TCTP immunostaining was also seen in human PAH lung sections, again associated with complex vascular lesions. In BOECs, TCTP was found to participate in cell growth and survival. These data suggest that TCTP could play an important role in PAH by mediating pro-survival and growth signaling in vascular cells, contributing to occlusive pulmonary vascular remodeling triggered by EC apoptosis.

Enlargement of adipocytes in obesity leads to alteration in adipokine production and these changes are linked to the development of obesity-related cardiovascular diseases. Adipokines specifically associated with obesity-related hypertension include angiotensinogen and adiponectin. Conjugated linoleic acid (CLA) has been reported to reduce blood pressure in obese insulin-resistant rats, but its mechanism of action has not been identified. The objective of this study was to determine whether CLA’s ability to improve obesity-related hypertension involves reducing adipocyte size and altering adipokine production. Fa/fa Zucker rats (6 or 16 week old) were fed diets containing CLA isomers for 8 weeks. The trans(t)10,cis(c)12-CLA isomer reduced adipocyte size in both younger and older rats. Despite beneficial changes in cell size of rats fed the t10,c12-CLA isomer, there were no changes in the renin-angiotensin system or pro-inflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 or the anti-inflammatory cytokine IL-10. In contrast, the t10,c12-CLA isomer increased adiponectin levels both in the circulation and in adipose tissue. This was associated with increased phosphorylation of endothelial nitric oxide synthase (eNOS) in adipose tissue and aorta. Direct treatment of CLA isomers in cultured endothelial cells did not increase eNOS phosphorylation but increases were observed with adiponectin treatment. In vivo, infusion with adiponectin increased eNOS phosphorylation in adipose of fa/fa Zucker rats in parallel with improvements in blood pressure. Similarly, when circulating levels of adiponectin increased in rats fed the t10,c12-CLA isomer diet, blood pressure was also attenuated. In younger rats, both the t10-c12 and c9,t11-CLA isomers were significantly different from the control group at week 8, however, only the t10,c12-CLA isomer was comparable to the commonly used anti-hypertensive medication captopril. In conclusion, the beneficial effects of the t10,c12-CLA isomer on blood pressure may in part be due to its ability to reduce the number of large adipocytes in vivo, thus increasing the production of adiponectin which subsequently activates vascular eNOS.

Resetting of baroreceptor afferent firing in hypertensive animals, and the reduction in baroreflex regulation of the heart rate seen in man, are thought to be secondary to changes in vascular distensibility in hypertension. Diminished baroreflex sensitivity should be reflected in a withdrawal of inhibition of sympathetic nervous function. This hypothesis was investigated in 62 hypertensive subjects using three indirect indices of sympathetic nervous activity: (1) the haemodynamic responses to mental and physical exercise, (2) plasma noradrenaline concentrations at rest, and on exercise, and (3) the beat-to-beat variability of waking ambulatory blood pressure. Subjects with diminished baroreflex sensitivity (1) achieved higher maximum mean arterial blood pressures during four different exercises, and greater absolute increases in blood pressure when bicycling, (2) tended (P<O.O6) to have higher plasma noradrenaline concentrations when bicycling, and (3) exhibited greater variability of their waking mean arterial pressure. It was concluded that subjects with reduced baroreflex sensitivity were less able to buffer acute changes in blood pressure, and inhibit sympathetic efferent activity, particularly when somatic afferents were also activated, as in physical exercise. The time course and extent of changes in baroreflex sensitivity, in relation to changes in the heart and (by inference from previous work) the peripheral vasculature, during the development and reversal of 2-kidney 1-clip Goldblatt hypertension was investigated in rats. A reduction in baroreflex sensitivity occurred within three days of renovascular hypertension, before the occurrence of cardiovascular changes and resetting of the threshold for carotid sinus activation. Baroreflex sensitivity returned to normal one day after the reversal of renovascular hypertension, at a time when these structural changes were still present. It was concluded that 'non-structural', rather than 'structural' factors were responsible for the reduction in baroreflex sensitivity during the initial stages of renovascular hypertension.

Background: Hypertension is a pathological increase in blood pressure that affects nearly 30% of the U.S. population and is a primary modifiable risk factor for cardiovascular disease. Despite advancements in prevention and treatment, hypertension is still one of the most common conditions around the world, and for a majority of cases the causal mechanisms remain to be fully elucidated. A growing body of literature suggests that oxidative stress status may play an etiological role in many chronic conditions, including hypertension. Specifically, a systemic overabundance of reactive oxygen species may give rise to endothelial dysfunction, increased sodium and H2O retention, and alterations in sympathetic outflow, leading to an increase in blood pressure. Purpose: The main objective of this study is to investigate the prospective association between F2-isoprostanes, a validated biomarker of oxidative status, and development of hypertension in a large, multi-centered, multi-ethnic cohort of adults aged 40-69 at baseline. Methods: This is a secondary data analysis that utilized previously collected data from the Insulin Resistance Atherosclerosis Study. 844 participants were included in the analysis. Briefly, four urinary F2-isoprostane isomers (F2-IsoP1, F2-IsoP2, F2-IsoP3, and F2-IsoP4) were quantified using liquid chromatography/ tandem mass spectrometry and adjusted for urinary creatinine levels. Hypertension was assessed at baseline and follow-up visits and defined as systolic blood pressure > 140 mm Hg and/or diastolic blood pressure > 90 mm Hg and/or currently taking antihypertensive medications. Crude associations between study population characteristics and hypertensive status were analyzed with the chi-square and Wilcoxon-rank sum tests. Crude associations between study population characteristics and F2-isoprostane levels were analyzed with Wilcoxon-rank sum, Kruskal-Wallis, and Spearman’s rank correlation measures. Finally, the adjusted prospective associations between hypertensive status and F2-isoprostane concentrations were modeled using logistic regression. Results: Of the 844 participants who were included in the study, 258 (31%) were classified as hypertensive at baseline. Among the 586 participants who were normotensive at baseline, 123 (21%) developed hypertension over the five-year study period. Importantly, none of four F2-isoprostane isomers predicted a significant increase in the odds of developing hypertension, as indicated by their odds ratio 95% confidence intervals; F2-IsoP1: (0.85, 1.31), F2-IsoP2: (0.62, 1.13), F2-IsoP3: (0.80, 1.27), and F2-IsoP4: (0.84, 1.29). Conclusion: Previous studies have investigated the association between oxidative status and hypertension prevalence, however the cross sectional nature of the study designs have made it difficult to establish temporality between exposure and outcome. To our knowledge, this is the first study to model the odds of developing hypertension as a function of F2-isoprostane levels. The results of this study suggest that oxidative status is not involved in the development of hypertension.

No description available.