It is well-recognized that a high salt diet contributes to the hypertension of hypertension of a significant number of individuals, particularly in the African-American (AA) population. What is not well-recognized is that mental stress can be a contributing factor to the sodium load in a significant percentage of the AAs. Our research indicates environmental stress has a greater impact than previously recognized on the sodium load and corresponding blood pressure load for African-Americans who increase reabsorption {i.e. retain) sodium during mental stress. Findings from our recently completed study in adults suggests that repeated episodes of mental stress throughout the day can increase the salt intake in these individuals by as much as a third over and above their already high salt diet. This study also showed the effect of stress on sodium retention and consequent increases in blood pressure could be mitigated by treatment with an angiotensin receptor antagonist. The proposed application will examine two additional pathways through which alone or in concert with angiotensin II promote sodium retention during mental stress in these individuals. The proposed studies will for the first time in this population: a) determine if this response is due to an increase in renal sympathetic nerve activity;b) determine if activation of the immune system contributes to the response pattern;and c), translate our previous findings on the effectiveness of an angiotensin II antagonist for an angiotensin 11-induced salt sensitive patient population into clinical practice. Synergy: Projects 1 and 2 will work in concert to better understand the role of the immune system in the development of stress-related hypertension. Projects 1 and 3 will continue their joint efforts to identify the mechanisms through which adiposity leads to impaired sodium handling, particularly during mental stress. Project 1 will also utilize all three cores for purposes of subject recruitment and testing {Core A), assays {Core B), and data analyses (Core C).

Public Health Relevance

effect of a high salt diet in African-Americans is well established. Our research provides evidence that stress contributes to this effect by inducing a significant additional sodium load over the course of a day. The overall goal of this proposal is to identify the mechanisms through which this occurs to help provide more effective prevention and treatment strategies for these individuals.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Heart, Lung, and Blood Program Project Review Committee (HLBP)
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Georgia Regents University
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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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