Robin W. Rockhold - US grants

It is postulated that the development of obesity exacerbates hypertensive disease in conjunction with changes in the activity of hypothalamic neurons which integrate sympatho-adrenal secretion in response to changes in plasma glucose concentrations. The opioid peptide, beta-endorphin, is a major determinant of the activity of such neurons within the paraventricular nucleus of the hypothalamus (PVH). This hypothesis will be tested in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats following selective lesioning of parvocellular PVH neurons by microinjection of the excitotoxin, N-methyl-D-aspartic acid (NMDA). Dietary obesity (DO) will be produced by feeding with a highly palatable diet. An initial series of experiments will correlate changes in hypothalamic beta-endorphin concentration (radioimmunoassay), plasma insulin levels (radioimmunoassay) and plasma catecholamine concentrations (HPLC-EC) with alterations in the rate of rise of blood pressure in sham or NMDA-lesioned SHR and WKY as DO develops. Specific hemodynamic and renal abnormalities associated with obesity-accelerated hypertension will be identified by measuring alterations in plasma volume (radio-iodinated serum albumin dilution) and baroreflex sensitivity in conscious, unrestrained rats following chronic (2 month) changes in diet. Relationships between plasma insulin levels, blood glucose regulation and reflex circulatory function will be examined during chronic DO following the challenge of insulin- induced hypoglycemia. Changes in distribution of regional blood flow (radio-labelled microspheres) and plasma catecholamine levels will be measured. The participation of renal sympathetic nerves in the observed responses to DO will be assessed in unlesioned SHR and WKY following renal denervation. Finally, comparisions will be made between the chronic circulatory changes caused by DO and the acute hemodynamic and plasma catecholamine responses triggered by discrete injection of beta- endorphin into the PVH of conscious SHR and WKY. The results will demarcate the role of a specific group of hypothalamic neurons in regulation of key metabolic and circulatory control systems using a novel experimental model of obesity-accelerated hypertension. The observed changes in hemodynamics, renal and sympatho-adrenal function may suggest more appropriate and effective therapeutic interventions.

biomedical equipment purchase;

? DESCRIPTION (provided by applicant): Science Teaching Excites Medical Interest (STEMI), a collaboration among University of Mississippi Medical Center (UMMC) biomedical research experts and graduate students, UMMC's nationally acclaimed Telehealth capacity, and K-12 Mississippi school districts, proposes a technology-enhanced, teacher- centered Community of Health Learners focused on public health topics of obesity and associated cardiovascular disease (CVD). The STEMI community will develop, evaluate the efficacy of and broadly disseminate high school learning products that address these issues. UMMC faculty in bioscience, anthropology, quantitative and qualitative data analysis, and program evaluation will guide high school science teachers from schools representative of the state's diversity of experiences and resources in new technological approaches with which to engage students in exploration of causal relationships among low health literacy, obesity, and ensuing anatomic and functional pathophysiology. STEMI will engage teachers in flipped learning/classroom (FL/C) science instruction, providing them with the tools to deliver to students' novel learning modules aligned with Next Generation Science Standards that specifically address CVD concerns directly impacted by nutrition and obesity. A UMMC anthropologist will facilitate networked approaches for creative teaching of social determinants of health, their impact on health disparities, and CVD. Summative, multisite, telecast presentations will also be created to broadly introduce school communities, peers and families to the STEMI Community of Health Learners. Four cadres of teachers will be guided through 2-year cycles of CVD-themed, didactic summer and weekend training aimed at: 1) design of FL/C explorations of obesity and health; 2) incorporation of classroom technology tools; and 3) electronic facilitation of interactive presentations on obesity, health literacy and CVD across school sites. These teachers, including 8 veterans in the first cycle and 8 early- midcareer teachers in the next 3 groups, will collaborate with UMMC graduate students in clinical anatomy (CA) to: 1) develop skills and practices that encourage entry into careers informed by biomedical sciences; 2) connect with peers and educators through projects that evaluate scientific findings; 3) learn methods for communicating public health issues; 4) gain fluency in state-of-the-art technologies; and 5) further technological collaborations that provide solutions to contemporary problems science education dilemmas. STEMI will validate a model collaborative training network, the structure and focus of which can be replicated by any academic health science center with a desire to advance Next Generation Science Standards and to promote excellence in STEM education.