This program project application consists of an integrated multidisciplinary program including 4 closely related projects examining the roles of stress, lifestyle behaviors and genetic polymorphisms in the development of preclinical measures of essential hypertension (EH). The Program Project is supported by 4 cores. Three vasoactive pathways will be examined which may link exaggerated cardiovascular (CV) reactivity and delayed CV recovery from stress to development of preclinical measures of EH. These pathways are Sympathetic Nervous System (SNS), Renin-Angiotensin-Aldosterone System (RAAS) and Endothelial System (ES). Project 1 involves the continued evaluation of youth with family histories of EH over a cumulative period of 17 years. Project 1 will focus upon the role of environmental stress (e.g., lower socioeconomic status, high personal life stress) in combination with 4 polymorphisms associated with the 3 vasoactive pathways (RAAS, SNS, ES) upon CV reactivity to acute laboratory challenges and development of preclinical measures of disease (e.g., increased left ventricular mass, increased resting blood pressure (BP), increased micro albumin, decreased endothelial function and increased arterial stiffness). Project 2 will examine possible ethnic differences in delayed BP recovery to an extended laboratory challenge primarily due to dysregulation of the RAAS system and ineffective sodium handling. Relationships between these parameters, 3 polymorphisms associated with SNS and RAAS and preclinical measures of disease will also be evaluated. Project 3 will examine impact of exercise training in African American children on BP reactivity to an acute laboratory challenge and preclinical measures of disease via improvements in the ES. Project 4 will be conducted on Dahl salt-sensitive rats and will assess the impact of intermittent stress and high salt diet upon vascular and renal mechanisms in the development of EH. It is designed to identify new candidate genes related to vascular and renal dysfunction associated with stress exposure. These four projects will each be supported by Bioassay (Core B), Biomedical (Core C) and Data Management and Statistics (Core D) cores.
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