The objective of Project 1 is to ascertain how chronic environmental stress and unfavorable genotypes, separately or in combination, affect BP reactivity to acute stress and subsequent increases in measures of preclinical essential hypertension (EH) and eventual development of EH. The roles of 3 vasoactive pathways will be examined (Sympathetic Nervous System [SNS], Renin- Angiotensin-Aldosterone System [RAAS], Endothelial System [ES]). The Project will study a cohort of 283 African American (AA) and 302 European American (EA) youth with positive family histories of EH who have been evaluated annually over a 12-year period. The continued follow-up of this cohort will allow us to examine the cumulative effects of environmental stress, genotypes and their interaction on the time course of the development of preclinical measures of EH over a period of 17 years. Subjects will have hemodynamic and vasoactive measures assessed during baseline, acute laboratory challenges and subsequent 30-minute recovery periods. Subjects will also have measures of preclinical EH evaluated including resting blood pressure (BP), left ventricular mass (LVM), endothelium dependent arterial dilation to reactive hyperemia (EDAD), arterial stiffness, micro albumin (micronALB) and 24-hour ambulatory BP. Four candidate genes affecting BP through the three vasoactive systems (SNS, RAAS, ES) will be studied.
The specific aims of Project 1 are to test the hypotheses that individuals from chronically stressful environments (e.g., lower SES, high personal life stress), or with unfavorable genotypes will exhibit greater increases over time in BP reactivity, measures of preclinical EH and vasoactive measures of RAAS, SNS and ES. Individuals combining stressful environments with unfavorable genotypes will exhibit even greater increases over time in these measures. Possible moderating influences of sex, ethnicity and lifestyle factors will also be examined. The long term objectives of Project 1 are to improve the understanding of the way stress contributes to the development of EH. Findings may contribute to development of pharmacogenetic approaches to the prevention and treatment of EH and will lead to more effective primary prevention programs involving lifestyle interventions in which the role of stress, both acute and chronic, will be taken into account, particularly for individuals at increased genetic risk of EH.
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