The overall goal of our PPG is to better understand the synergy between environmental stress, adiposity, and impaired sodium regulation in the development of hypertension in high risk populations. Three projects are proposed supported by three Cores (Administrative, Bioassay, Biostatistics). Each of the three projects we propose has a unique focus, but they also have commonalities across the projects. The high synergy and integration allows us to apply information gained from one project to the understanding of the results of another. All three projects hypothesize a central role for SNS-induced changes in Ang II as a mediator of impaired functioning. In addition, all three projects will focus on understanding the physiological mechanisms through which stress and obesity contribute to hypertension in African Americans. Projects 1 and 3 will examine different pathways in human and animal models. Specifically, Project 1 hypothesizes Ang II is one factor responsible for sodium retention during stress in African Americans which leads to the early development of hypertension. These studies are complimented by Project 3 that will focus on the ETB receptor and use in whole body sodium retention. Project 2 will examine the impact of early life stress on Ang H-related functioning of the immune system and the development of hypertension in animal models. This stimulated Project 1 to explore this relationship in our human model of hypertension in African Americans. Projects 2 and 3 will both examine factors related to endothelial function in different models of obesity-related disease. Taken together, there is strong synergy between the projects that will allow us to identify critical factors in obesity and stress-related hypertension. More importantly, they will allow us to identify the mechanisms underlying the synergistic effect of obesity on stress-related hypertension.

Public Health Relevance

to Public Health: Essential hypertension is the number 1 reason for a physician visit, with 1 in 3 people suffering from the disorder. Our studies seek to identify the mechanisms underlying for the synergy between 3 of the most important risk factors for hypertension. This knowledge will enable us to develop more effective prevention and treatment strategies.

Agency
National Institute of Health (NIH)
Type
Research Program Projects (P01)
Project #
2P01HL069999-11A1
Application #
8667155
Study Section
Heart, Lung, and Blood Program Project Review Committee (HLBP)
Program Officer
Kaufmann, Peter G
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Georgia Regents University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
City
Augusta
State
GA
Country
United States
Zip Code
30912
Pollock, David M (2014) 2013 Dahl Lecture: American Heart Association council for high blood pressure research clarifying the physiology of endothelin. Hypertension 63:e110-7
Su, Shaoyong; Zhu, Haidong; Xu, Xiaojing et al. (2014) DNA methylation of the LY86 gene is associated with obesity, insulin resistance, and inflammation. Twin Res Hum Genet 17:183-91
Riese, Harriëtte; Muñoz, Loretto M; Hartman, Catharina A et al. (2014) Identifying genetic variants for heart rate variability in the acetylcholine pathway. PLoS One 9:e112476
Hyndman, Kelly A; Ho, Dao H; Sega, Martiana F et al. (2014) Histone deacetylase 1 reduces NO production in endothelial cells via lysine deacetylation of NO synthase 3. Am J Physiol Heart Circ Physiol 307:H803-9
Su, Shaoyong; Wang, Xiaoling; Kapuku, Gaston K et al. (2014) Adverse childhood experiences are associated with detrimental hemodynamics and elevated circulating endothelin-1 in adolescents and young adults. Hypertension 64:201-7
Jin, Chunhua; Jeon, Yejoo; Kleven, Daniel T et al. (2014) Combined endothelin a blockade and chlorthalidone treatment in a rat model of metabolic syndrome. J Pharmacol Exp Ther 351:467-73
Kittikulsuth, W; Sullivan, J C; Pollock, D M (2013) ET-1 actions in the kidney: evidence for sex differences. Br J Pharmacol 168:318-26
Loria, Analia S; Brands, Michael W; Pollock, David M et al. (2013) Early life stress sensitizes the renal and systemic sympathetic system in rats. Am J Physiol Renal Physiol 305:F390-5
Spradley, F T; Kang, K-T; Pollock, J S (2013) Short-term hypercaloric diet induces blunted aortic vasoconstriction and enhanced vasorelaxation via increased nitric oxide synthase 3 activity and expression in Dahl salt-sensitive rats. Acta Physiol (Oxf) 207:358-68
Kittikulsuth, Wararat; Looney, Stephen W; Pollock, David M (2013) Endothelin ET(B) receptors contribute to sex differences in blood pressure elevation in angiotensin II hypertensive rats on a high-salt diet. Clin Exp Pharmacol Physiol 40:362-70

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