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Obesity is associated with sympathetic neural activation and elevated blood pressure(1,2). However, it is unclear whether modest elevations in body weight are sufficient to induce increases sympathetic activity (3). Furthermore, there is a large amount of individual variability in the blood pressure response to weight change (4). The reason(s) for this inter-individual variability are still uncertain, but body fat distribution and cardiorespiratory fitness may play a role (5,6). To address these and other issues regarding the relation between adiposity, sympathetic neural activity and blood pressure, we first examined the effects of modest, diet-induced weight gain on muscle sympathetic nervous system activity (MSNA) in healthy, lean, normotensive individuals. We hypothesized that modest weight gain would increase MSNA in these individuals, and that this neural activation would be accompanied by increases in blood pressure. Concordant with this hypothesis, MSNA and resting blood pressure were significantly elevated following weight gain. The increase in MSNA was correlated with the magnitude of body weight and fat gain, but was not obviously related to increases in visceral fat. We next examined the ability of cardiorespiratory fitness (CRF) to modulate the weight gain-induced increase in blood pressure in the same cohort of young, nonobese and normotensive individuals. We hypothesized that the increase in blood pressure would be attenuated in individuals with higher- compared with lower CRF (HCRF and LCRF, respectively). Indeed, we found that HCRF experienced significantly smaller increases in resting and ambulatory blood pressure compared to LCRF. In the pooled sample, baseline fitness was inversely related to the changes in resting systolic and diastolic pressure, and this relation was not diminished after statistically controlling for changes in abdominal visceral fat. The results of the present investigation suggest that even modest weight gain increases sympathetic activity and blood pressure, which, if left untreated, may contribute to the development of hypertension and other cardiovascular disorders. Maintenance of higher levels of CRF during periods of weight gain may reduce cardiovascular disease risk by mitigating the increases in blood pressure. Collectively, these findings may have important implications for understanding the link between obesity and hypertension. References 1. Davy KP. The global epidemic of obesity: are we becoming more sympathetic? Curr Hypertens Rep. 2004;6:241-6. 2. Grassi G, Seravalle G, Cattaneo BM, et al. Sympathetic activation in obese normotensive subjects. Hypertension. 1995;25:560-3. 3. Huggett RJ, Scott EM, Gilbey SG, Bannister J, Mackintosh AF, Mary DA. Disparity of autonomic control in type 2 diabetes mellitus. Diabetologia. 2005;48:172-9. 4. Masuo K, Mikami H, Ogihara T, Tuck ML. Weight gain-induced blood pressure elevation. Hypertension. 2000;35:1135-40. 5. Hayashi T, Boyko EJ, Leonetti DL, et al. Visceral adiposity is an independent predictor of incident hypertension in Japanese Americans. Ann Intern Med. 2004;140:992-1000. 6. Barlow CE, LaMonte MJ, Fitzgerald SJ, Kampert JB, Perrin JL, Blair SN. Cardiorespiratory fitness is an independent predictor of hypertension incidence among initially normotensive healthy women. Am J Epidemiol. 2006;163:142-50. / Ph. D.

The primary goal of this project was to develop, implement, and evaluate a lifestyle modification intervention that did not require extensive, ongoing personal contact to improve lifestyle behaviors shown to lower blood pressure (BP) in adults with prehypertension (N=23, mean age=54, mean BP=126.7/75.1). Incorporating clinical practices and psychological approaches to behavior change, this intervention used primarily the DASH Eating Plan, coupled with a low-sodium diet and a walking program; it applied social cognitive theory to health behavior change, specifically self-regulation for self-monitoring and management of BP, diet, exericse, and weight. The study compared two conditions, the DASH 2 Wellness Only standard of care condition to the DASH 2 Wellness Plus treatment condition on the primary outcome measures of fruit and vegetable (servings/day), sodium consumption (milligrams/day), physical activity (steps/day), weight (kgs), and blood pressure (primarily systolic BP). Consistent with hypotheses, MANOVAs detected significant differences between the conditions with D2W Plus evidencing a larger increase in change of total daily steps (M= 2900.14, SD= 1903.83) than D2W Only, (M= 636.39, SD= 1653.26), a larger decrease in systolic BP change (MMHG) (M= 15.14, SD= 4.33) than D2W Only, (M= 4.61, SD= 8.28), and a larger decrease in weight change (kg) (M= 4.78, SD= 3.81) than D2W Only, (M= 1.47, SD= 2.57). While conditions did not significantly differ on daily sodium reduction or fruit and vegetable increase, D2W Plus evidenced a larger decrease in sodium (mg) (M= 932.22, SD= 1019.22) than D2W Only, (M= 423.64, SD= 749.15) and larger increase in fruit and vegetable increase, (M= 2.10, SD= 1.73) than D2W Only, (M= 1.02, SD= 2.24). It was also hypothesized that the D2W Plus condition would show greater improvements in nutrition-specific and PA-specific health beliefs of self-regulation, social support, self-efficacy, social support, and outcome-expectancy compared to those in the D2W Only condition. A MANOVA revealed significant group differences in PA-specific health beliefs primarily attributable to increased PA self-regulation in D2W Plus compared to D2W Only, (M= 1.78, SD= 0.75) and (M= 0.55, SD= 0.57), respectively. While no overall significant group differences were found for nutrition-specific health beliefs, analyses showed meaningful differences in nutrition-specific health beliefs attributable to increased nutrition self-regulation strategies in D2W Plus compared to D2W Only. Results provide preliminary support for the efficacy of an electronic delivery of an intervention aimed at improving lifestyle behaviors and lowering BP in middle-aged individuals with prehypertension. / Ph. D.

Data were collected from the initial symptom-limited maximal exercise tests of 161 patients without. diagnosed coronary heart disease (CHD). Subjects were grouped according to their systolic (SBP) and diastolic (DBP) blood pressure changes between the final two stages of exercise. / Master of Science

Twelve obese normotensive females were studied to determine the effects of either a 71% carbohydrate (HC) hypocaloric diet or a 33% carbohydrate (LC) hypocaloric diet concommitant with an aerobic exercise program on sodium (Na) balance and blood pressure changes. Subjects participated three times a week in a submaximal periodic exercise session and were placed on one of the diets for 28 days. Posttreatment, each participant consumed a 1000 kcal mixed diet while remaining in the exercise program. Daily Na losses were measured by 24 hr urine collection, and blood pressure measurements were made weekly. Both treatment groups significantly decreased in weight with LC losing more than HC (8.0 kg by LC group; 6.7 kg by HC group). Although urine Na balance was negative for the first 2 days of both VLCD's, Na excretion fell over time to result in net Na retention over the experimental period. Though the LC group lost more Na during the first week than EC during subsequent weeks, the differences between groups were nonsignificant. There were no significant differences between groups in serum Na or urine Na balance. However, Na urinary loss significantly decreased across time. Both systolic and diastolic blood pressure decreased non-significantly an average of 4% from baseline values throughout the treatment (5.2/4.0 mmHg in the HC group and 4.3/2.3 mmHg in the LC group). Carbohydrate inclusion in both diets was found to be effective in retaining Na after 4 days on a VLCD. Changes on different postural positions did not reveal evidence of hypotension. Overweight normotensive individuals did not reduce blood pressure values below normal levels. / M.S.

Thirteen male college students volunteered to participate in this study. All subjects were students at Virginia Tech University and were between the ages of 18 and 34. The subjects were studies to determine their blood pressure responses to two weight lifting movements. Statistical significance was found for all conditions of systolic blood pressure and for peak diastolic blood pressure. It was concluded by the investigator that systolic blood pressure response is positively affected by both the mode of exercise and the loading of the exercise. / M.S.

Yes / There is an increased evidence for treating hypertension by a combination of two or more drugs. Increasing the number of daily intake of tablets has been reported to negatively affect the compliance of patients. Therefore, numerous fixed dose combinations (FDCs) have been introduced to the market. However, the inherent rigid nature of FDCs does not allow the titration of the dose of each single component for an individual patient's needs. In this work, flexible dose combinations of two anti-hypertensive drugs in a single bilayer tablet with a range of doses were fabricated using dual fused deposition modelling (FDM) 3D printer. Enalapril maleate (EM) and hydrochlorothiazide (HCT) loaded filaments were produced via hot-melt extrusion (HME). Computer software was utilised to design sets of oval bi-layer tablets of individualised doses. Thermal analysis and x-ray diffractometer (XRD) indicated that HCT remained crystalline in the polymeric matrix whilst EM appeared to be in an amorphous form. The interaction between anionic EM and cationic methacrylate polymer may have contributed to a drop in the glass transition temperature (Tg) of the filament and obviated the need for a plasticiser. Across all tablet sets, the methacrylate polymeric matrix provided immediate drug release profiles. This dynamic dosing system maintained the advantages of FDCs while providing a superior flexibility of dosing range, hence offering an optimal clinical solution to hypertension therapy in a patient-centric healthcare service.

Yes / Ambulatory and/or home monitoring are recommended in the UK and North America for the diagnosis of hypertension but little is known about acceptability. To determine the acceptability of different methods of measuring blood pressure to people from different ethnic minority groups. Design and setting : Cross sectional study with focus groups in primary care. Methods: People with and without hypertension of different ethnicities were assessed for acceptability of clinic, home and ambulatory blood pressure measurement using completion rate, questionnaire and focus groups. Results: 770 participants were included comprising white British (n=300), South Asian (n=241) and African Caribbean (n=229). White British participants had significantly higher successful completion rates across all monitoring modalities compared to the other ethnic groups, especially for ambulatory monitoring: white British (277 completed, 92%[89-95%]) vs South Asian (171, 71%[65-76%], p<0.001 and African Caribbean (188, 82%[77-87%], p<0.001) respectively. There were significantly lower acceptability scores for minority ethnic participants across all monitoring methods compared to white British. Focus group results highlighted self-monitoring as most acceptable and ambulatory monitoring least without consistent differences by ethnicity. Clinic monitoring was seen as inconvenient and anxiety provoking but with the advantage of immediate professional input. Conclusions: Reduced acceptability and completion rates amongst minority ethnic groups raise important questions for the implementation and interpretation of blood pressure monitoring in general and ambulatory monitoring in particular. Selection of method for blood pressure monitoring should take into account clinical need and patient preference as well as consideration of potential cultural barriers to monitoring. / NIHR

Prolonged exposure to microgravity is known to invoke physiological changes which predispose individuals to orthostatic intolerance upon readaptation to the earth's gravitational field. Attenuated baroreflex responsiveness has been implicated in contributing to this inability to withstand orthostatic stress. To test this hypothesis, eight individuals were exposed to 15 days of simulated microgravity exposure using the 6° head-down bed rest model. Prior to, and after the simulated microgravity exposure, the following were assessed: a) aortic baroreflex function; b) carotid baroreflex function; c) cardiopulmonary baroreflex function; and d) the degree of interaction between the cardiopulmonary and carotid baroreflexes.

Baroreflex function and cardiovascular responses to lower body negative pressure during selective autonomic blockade were evaluated in endurance exercise trained (ET) and untrained (UT) men. Baroreflex function was evaluated using a progressive intravenous infusion of phenylephrine HCL (PE) to a maximum of 0.12 mg/min. Heart rate, arterial blood pressure, cardiac output and forearm blood flow were measured at each infusion rate of PE. The reduction in forearm blood flow and concomitant rise in forearm vascular resistance was the same for each subject group. However, the heart rate decreases per unit increase of systolic or mean blood pressure were significantly (P<.05) less in the ET subjects (0.91 ± 0.30 versus 1.62 ± 0.28 for UT). During progressive lower body negative pressure with no drug intervention, the ET subjects had a significantly (P<.05) greater fall in systolic blood pressure (33.8 ± 4.8 torr versus 16.7 ± 3.9 torr). However, the change in forearm blood flow or resistance was not significantly different between groups. Blockade of parasympathetic receptors with atropine (0.04 mg/kg) eliminated the differences in response to lower body negative pressure. Blockade of cardiac sympathetic receptors with metoprolol (0.02 mg/kg) did not affect the differences observed during the control test. It was concluded that the ET subjects were less effective in regulating blood pressure than the UT subjects, because of 1) an attenuated baroreflex sensitivity, and 2) parasympathetic-mediated depression of cardiac and vasoconstrictive responses to the hypotensive stress.