Impaired stress-induced pressure natriuresis is approximately twice as prevalent in black as in white youth. Salt, stress and genetics are three of the factors hypothesized to account for the difference. The proposed project will extend previous investigations in this area that focused on hormonal responses by identifying genetic predispositions responsible for impaired stress-induced pressure natriuresis. The overall goal is to determine the role of genes involved in the sodium-handling cascade in the renal tubules on dynamic regulation of sodium homeostasis and blood pressure under stress in blacks. These include five genes encoding the epithelial sodium channel (alpha ENaC, beta ENaC and gamma ENaC) and its accessory regulatory proteins such as serum glucocorticoid-inducible kinase (SGK-1) and neural precursor cell-expressed developmentally down-regulated 4 (Nedd4-2). The concerted Nedd4-SGK-ENaC interaction plays an important role in ENaC activity and tubular sodium handling. Environmental stress may promote sodium retention via intrinsic ENaC activity. Therefore, the primary aims are to test the following hypotheses in black youth; individuals with unfavorable genotypes or haplotypes compared to those without will show 1) a reduced stress-induced increase in urinary sodium excretion; 2) delayed systolic blood pressure recovery following stress; and 3) greater plasma renin activity suppression (low-renin hypertension) during recovery following stress. The secondary aim is to explore gene-gene interactions among the five genes consisting of the ENaC pathway in relation to the three primary outcome variables. A total of 300 black youth will be studied which will include an equal number of boys and girls aged 15-19 yrs. All subjects will be tested with an extended stress protocol including a recovery period. Single nucleotide polymorphisms (SNPs) in the five genes will be systematically examined in these subjects using both direct (i.e., functional SNPs) and indirect (i.e., haplotype tagging SNPs) association approaches. Buccal cell DNA from the parents of these youth will be collected to facilitate (1) haplotype reconstruction and analyses and (2) transmission disequilibrium tests (TDTs). Classification and Regression Trees techniques will be used to explore possible gene-gene interactions. This proposed research will provide novel insight into the interactions between genetics, salt and environmental stress, and their contribution to the pathogenesis of essential hypertension. The project aims to investigate the influence of salt, stress and genes on the body's ability to release sodium. Understanding the connections between salt, stress and genetics will provide a fresh approach into evaluating risk factors for high blood pressure. ? ? ?

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Kaufmann, Peter G
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Georgia Regents University
Schools of Medicine
United States
Zip Code
Stewart, Deborah; Dong, Yanbin; Zhu, Haidong et al. (2017) Angiotensin II-Mediated Increases in Damage-Associated Molecular Patterns During Acute Mental Stress. Psychosom Med 79:112-114
Bhagatwala, Jigar; Zhu, Haidong; Parikh, Samip J et al. (2015) Dose and time responses of vitamin D biomarkers to monthly vitamin D3 supplementation in overweight/obese African Americans with suboptimal vitamin d status: a placebo controlled randomized clinical trial. BMC Obes 2:27
Guo, De-huang; Parikh, Samip J; Chao, Julie et al. (2013) Urinary prostasin excretion is associated with adiposity in nonhypertensive African-American adolescents. Pediatr Res 74:206-10
Pierce, Gary L; Zhu, Haidong; Darracott, Katherine et al. (2013) Arterial stiffness and pulse-pressure amplification in overweight/obese African-American adolescents: relation with higher systolic and pulse pressure. Am J Hypertens 26:20-6
Lucas, Rudolf; Parikh, Samip J; Sridhar, Supriya et al. (2013) Cytokine profiling of young overweight and obese female African American adults with prediabetes. Cytokine 64:310-5
Wang, Xiaoling; Falkner, Bonita; Zhu, Haidong et al. (2013) A genome-wide methylation study on essential hypertension in young African American males. PLoS One 8:e53938
Zhu, Haidong; Wang, Xiaoling; Shi, Huidong et al. (2013) A genome-wide methylation study of severe vitamin D deficiency in African American adolescents. J Pediatr 162:1004-9.e1
Parikh, Samip; Guo, De-Huang; Pollock, Norman K et al. (2012) Circulating 25-hydroxyvitamin D concentrations are correlated with cardiometabolic risk among American black and white adolescents living in a year-round sunny climate. Diabetes Care 35:1133-8
Pollock, Norman K; Bundy, Vanessa; Kanto, William et al. (2012) Greater fructose consumption is associated with cardiometabolic risk markers and visceral adiposity in adolescents. J Nutr 142:251-7
Zhu, H; Guo, D; Li, K et al. (2012) Increased telomerase activity and vitamin D supplementation in overweight African Americans. Int J Obes (Lond) 36:805-9

Showing the most recent 10 out of 23 publications