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)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
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
2002-07-01
Project End
2019-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
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
De Miguel, Carmen; Speed, Joshua S; Kasztan, Malgorzata et al. (2016) Endothelin-1 and the kidney: new perspectives and recent findings. Curr Opin Nephrol Hypertens 25:35-41
Heimlich, J Brett; Speed, Joshua S; O'Connor, Paul M et al. (2016) Endothelin-1 contributes to the progression of renal injury in sickle cell disease via reactive oxygen species. Br J Pharmacol 173:386-95
Davenport, Anthony P; Hyndman, Kelly A; Dhaun, Neeraj et al. (2016) Endothelin. Pharmacol Rev 68:357-418
Gohar, Eman Y; Giachini, Fernanda R; Pollock, David M et al. (2016) Role of the endothelin system in sexual dimorphism in cardiovascular and renal diseases. Life Sci 159:20-9
Spradley, Frank T; Ho, Dao H; Pollock, Jennifer S (2016) Dahl SS rats demonstrate enhanced aortic perivascular adipose tissue-mediated buffering of vasoconstriction through activation of NOS in the endothelium. Am J Physiol Regul Integr Comp Physiol 310:R286-96
Guan, Zhengrong; Singletary, Sean T; Cha, Haword et al. (2016) Pentosan polysulfate preserves renal microvascular P2X1 receptor reactivity and autoregulatory behavior in DOCA-salt hypertensive rats. Am J Physiol Renal Physiol 310:F456-65
Heimlich, J B; Speed, J S; Bloom, C J et al. (2015) ET-1 increases reactive oxygen species following hypoxia and high-salt diet in the mouse glomerulus. Acta Physiol (Oxf) 213:722-30
Su, Shaoyong; Wang, Xiaoling; Pollock, Jennifer S et al. (2015) Adverse childhood experiences and blood pressure trajectories from childhood to young adulthood: the Georgia stress and Heart study. Circulation 131:1674-81
Speed, Joshua S; Fox, Brandon M; Johnston, Jermaine G et al. (2015) Endothelin and renal ion and water transport. Semin Nephrol 35:137-44
Speed, Joshua S; Pollock, David M (2015) New clues towards solving the mystery of endothelin and blood pressure regulation. Hypertension 66:275-7

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