Thesis (M.S.)--University of Michigan, 1997. / Includes bibliographical references.

Thesis (M.S.)--University of Michigan, 1999. / Running title: Cognitive representations of hypertension. Includes bibliographical references.

Thesis (M.S.)--University of Michigan, 1983.

Thesis (Ph.D.)--Memorial University of Newfoundland, 2004. / Bibliography: leaves 152-185.

Thesis (Ph.D.)--University of California, San Francisco, 2004. / Includes bibliographical references. Also available online.

FundaÃÃo de Amparo à Pesquisa do Estado do Cearà / The identification of patients with arterial hypertension, and the attitudes and practices related to individual cases of the condition, are fundamental to its control and to the prevention of associated complications. The dyslipidemia and hypertension are common and powerful risk factors for cardiovascular disease (CVD) and often coexist in the same individual. The diuretics and beta blockers affect the lipid profile and they can act synergistically, with dyslipidemia and hypertension, in terms of increased risk for CVD. We investigated the influence of hypertension and its treatment on circulating lipids. One hundred and sixty-nine individuals with aged between 32-87 years were studied. According to the results the population was predominantly women (72,6%), and the subjects had a mean blood pressure of 144,23  14,86 (mean  SD) for systolic pressure, and 90,45  9,91 for diastolic pressure. Hydrochlorothiazide (HCTZ), captopril (CPT) and propranolol (PPL) were the most prescribed drugs. Monotherapy was used in 33,53% of the patients, and CPT was the most prescribed drug. In association therapy (66,47%) the most used drug was HCTZ, specially in prescriptions associated to CPT. Propranolol was used proportionally more by women (p=0,01) and verapamil more by men (p=0,009), and the control of hypertension was significantly (p=0,04) more frequent in individuals being treated with monotherapy than in the subjects being treated with combination therapy. Patients taking HCTZ had significant effects in theirs lipid serum concentrations while that ones taking CPT and/or PPL have no expressive effects. The main associations which lead to lipid serum alterations were HCTZ+CPT and HCTZ+PPL. Theses results suggest that any therapy with includes HCTZ as an hypertensive drug, must be associated to a lipid monitoring process / A identificaÃÃo de pacientes com hipertensÃo arterial, as atitudes e as prÃticas face aos casos individuais sÃo determinantes para o controle da doenÃa e prevenÃÃo e para prevenÃÃo das complicaÃÃes associadas. Dislipidemia e hipertensÃo sÃo comuns e poderosos fatores de risco para doenÃas cardiovasculares e freqÃentemente coexistem num mesmo indivÃduo. Os diurÃticos e beta bloqueadores elevam o perfil lipÃdico e podem agir sinergicamente, com dislipidemia e hipertensÃo, na elevaÃÃo dos riscos para doenÃas cardÃacas. NÃs investigamos a influÃncia da hipertensÃo e seu tratamento sobre os lipÃdios circulantes. Foram estudados 169 indivÃduos, com idades entre 32 â 87 anos. De acordo com os resultados obtidos, a maioria da populaÃÃo foi composta por mulheres (72,6%), e a mÃdia de pressÃo era 144,23  14,86 (mÃdia  DP) para pressÃo sistÃlica e 90,45  9,91 para pressÃo diastÃlica. Hidroclorotiazida (HCTZ), captopril (CPT) e propranolol (PPL) foram as drogas mais prescritas. Monoterapia foi utilizada por 33,53% dos pacientes, e captopril foi a droga mais prescrita. Em associaÃÃo (66,47%) a droga mais prescrita foi HCTZ, principalmente associada com CPT. Propranolol foi predominantemente utilizada no sexo feminino (p= 0,01) e verapamil no sexo masculino (p=0,009), sendo que o controle da hipertensÃo foi significativamente (p=0,04) mais freqÃente nos indivÃduos tratados com monoterapia do que naqueles em uso de associaÃÃo. Pacientes em uso de hidroclorotiazida tiveram efeitos significantes sobre as concentraÃÃes sÃricas de lipÃdios, enquanto aqueles em uso de CPT e/ou PPL nÃo apresentaram efeitos expressivos. As principais associaÃÃes que elevaram lipÃdeos sÃricos foram HCTZ+CPT e HCTZ+PPL. Estes resultados sugerem que quando a terapÃutica antihipertensiva envolver o uso de HCTZ, a monitorizaÃÃo do perfil lipÃdico se faz necessÃria.

Male (8) and female (22) Essential Hypertensives (130/85 mm Hg or above) were randomized into a nonspecific treatment or an experimental treatment utilizing eight relaxation strategies. Both groups had eight training sessions which consisted of baseline blood pressures (BP), 15 minute relaxation tapes, and post-relaxation BP's. Subjects were instructed to use their tapes three times between sessions. Five BP readings were taken at the one and two month follow-ups. It was hypothesized that the experimentals would have greater within and across session decreases in BP, and that the differences would be maintained during a no treatment follow-up. Eleven experimentals and 8 controls were on medication. Mean medication compliance percentages were 99.9 and 99.6 while mean relaxation compliance percentages were 95.2 and 115.2 for experimentals and controls respectively. Efficacy was checked at each training session on a seven-point scale and group means were 6.5 and 5.4 for experimentals verses controls. Within session decreases in BP were compared with t tests and no significant differences (p < .05) were present for the eight training sessions with systolic (SBP) or diastolic (DBP). Across session changes were compared with ANCOVA and no significant differences (p < .05) were present for the eight training or two follow-up sessions for SBP or DBP. In summary, the experimentals showed within and across session decreases in BP consistent with prior research, but the effect was not significantly better than "sitting quietly". It was concluded that nonspecific treatments must be included in BP research on effectiveness of treatments. A final conclusion was that both groups did show clinically useful decreases in BP which were maintained at follow-up and the effectiveness of noninvasive treatments for Essential Hypertension was demonstrated.

The isolated perfused working heart was used to study hypertensive- diabetes induced alterations in cardiac function at 6 and 12 weeks after the induction of diabetes. There was no difference in cardiac function between normotensive Wistar and spontaneously hypertensive (SHR) diabetic rats at 6 weeks after diabetes induction. Wistar-Kyoto (WKY) rats were also included as normotensive controls in our 12-week study. Successful induction of diabetes was confirmed by the presence of hyperglycemia, hypoinsulinemia, glycosuria and increased haemoglobin glycosylation in all three diabetic groups. However, quantitation of various parameters of heart function revealed highly significant differences between SHR diabetic animals and all other groups, associated with an increased mortality. Serum lipids were elevated in SHR and Wistar and unaffected in WKY diabetic rats. Furthermore, thyroid hormone levels were not depressed in WKY diabetic rats and could explain the lack of cardiac dysfunction in these animals. The data provide further evidence that the combination of hypertension and diabetes mellitus produces greater myocardial dysfunction than is seen with either disease alone and is associated with a significant mortality. The effects of hydralazine on blood lipids, systolic pressure and cardiac performance were assessed in male Wistar rats, 6 weeks after they were made diabetic with streptozotocin (STZ). When hydralazine was administered for a 6-week period to the diabetic rats, their blood lipids were not significantly different from that of non-diabetic rats despite a low serum insulin. In contrast, blood lipids were elevated in the diabetic rats that were not treated with hydralazine; these animals also had low insulin levels. Cardiac performance was depressed in the untreated diabetic animals, but the cardiac performance of the hydralazine-treated diabetic animals showed a definite improvement which could be partly explained by their normal thyroid status in contrast to the untreated diabetic animals which were slightly hypothyroid. Blood pressure was elevated only in the untreated diabetic animals. Thus hydralazine controlled the high serum lipids and blood pressure and improved cardiac performance in STZ diabetic rats. To examine the influence of sex differences in the STZ model of diabetes, we studied left ventricular function in hearts from 6 week male and female rats. Significantly lower values for +dP/dt occurred in male diabetic rats compared with their own controls or female diabetics at most left atrial filling pressures. Decreases in this value for female diabetic rats compared to their own controls occurred only at high left atrial pressures. It appears that diabetes mellitus produces greater myocardial dysfunction in male diabetic rats. / Pharmaceutical Sciences, Faculty of / Graduate

High blood pressure or hypertension is a major public health issue that affects more than 50% of adults in the United States. Hypertension is the leading risk factor for multiple cardiovascular events including stroke and myocardial infarction. In general, hypertension is considered a disease of the aged population as 2/3rds of adults over 65 are hypertensive. Critically, a sex dependent component exists as females under age 50 are less likely to develop hypertension than males. Dietary sodium intake significantly influences blood pressure regulation and its importance is underscored by the salt-sensitivity of blood pressure, which is characterized by acute increases in blood pressure in response to dietary salt intake. The salt-sensitivity of blood pressure is prevalent in 25% of normotensive individuals and 50% of hypertensive individuals. Coupled with statistics that show Americans on average consume 2 g of sodium in excess of the recommended daily allowance, the risk for developing salt-sensitive hypertension is drastically higher in salt-sensitive individuals. Moreover with age, there is an increase in the prevalence and severity of salt-sensitivity. Taken together, these findings underscore the need for novel therapeutics to combat hypertension. The pathophysiology of the salt-sensitivity of blood pressure and age dependent hypertension has been attributed in part to excessive sympathetic outflow that can drive increases in sodium reabsorption. Excessive sympathetic outflow via the release of norepinephrine has been linked to increased activity of a key renal sodium transporter, the sodium chloride cotransporter (NCC). This thesis investigates the adrenergic signaling pathway by which excessive sympathetic outflow drives NCC activity and sodium reabsorption as well investigates the mechanisms underlying sex differences in age dependent hypertension. Our findings demonstrate that 1) norepinephrine mediates its influence on NCC activity via an α1-adrenoceptor gated pathway involving WNK/SPAK/OxSR1 kinase signaling, 2) α1-adrenoceptor antagonism can prevent and attenuate the development and maintenance of salt-sensitive hypertension, 3) β-adrencoptor antagonism has no effect on NCC activity, 4) in male rats age dependent salt-sensitivity of blood pressure and hypertension is associated with age dependent- increases in NCC activity and impairments in renal sodium handling, and 5) female rats do not develop age dependent hypertension or salt-sensitivity of blood pressure. Collectively, these results support a sympathetic model of NCC regulation that plays a key role in salt-sensitive hypertension and age dependent hypertension. / 2021-05-26T00:00:00Z

La physiopathologie des hypertensions pulmonaires (HP) reste encore imparfaitement comprise. Plusieurs mécanismes interviennent dans le développement et la progression du remodelage vasculaire pulmonaire. Les perturbations de communications intercellulaires et l’activation de certaines voies de signalisation sont des phénomènes importants contribuant à l’accumulation excessive de cellules au sein de la paroi des petites artères pulmonaires.Par ailleurs, des facteurs génétiques et environnementaux peuvent prédisposer ou faciliter la progression de ce remodelage vasculaire.L’existence de modifications des micro-vaisseaux pulmonaires pré- et post-capillaires et bronchiques dans l’hypertensionn pulmonaire post-embolique et l’hypertension artérielle pulmonaire represente un aspect nouveau de ces deux maladies et permettra d’améliorer sur le long terme la prise en charge de ces patients. Ces altérations vasculaires sont aussi présentes dans deux modèles animaux d’étude d’hypertension pulmonaire, validant la pertinence d’approfondir nos connaissances au travers de ces outils expérimentaux. / The pathophysiology of pulmonary hypertension (PH) remains unclear. Différent mechanisms are involved in the vascular remodeling in PH. The disruption of cellular interactions and the activation of specific signalling pathways contribute to the development and progression of the structural changes in small pulmonary arteries. Moreover, environmental and genetic factors may predispose to this vascular disease.The alterations of pulmonary micro-vessels and of bronchial circulation in chronic thromboembolic disease and in pulmonary arterial hypertension represent a new finding in such diseases, with potential implications in the managment of patients. Pulmonary microvascular changes and bronchial circulation remodeling are also idenfied in selected animal models of PH.