The renewal application for this project will follow-up the findings of the parent grant and previous studieswhich suggest: 1) African-Americans have an impaired natriuretic response to stress; 2) this pattern isrelated to the functioning of the renin-angiotensin-aldosterone system; and 3) is associated with the earlydevelopment of target organ damage. In addition, these studies 4) indicate increased adiposity contributesto the pattern.
Specific Aims 1 and 2 will examine the effects of an angiotensin receptor blocker on thepressure natriuresis response to stress in African-Americans with impaired stress-induced pressurenatriuresis, confirming the role of angiotensin II in the response pattern. Furthermore, this effect will becompared in normal weight versus overweight individuals, with a hypothesized greater effect in overweightsubjects.
Aim 3 will compare the effects of an angiotensin receptor blocker between carriers and noncarriersof a functional polymorphism of the angiotensin II receptor type 1 gene. These results will provideadditional evidence for the mechanistic role of angiotensin II and continue our gene/environmental approachto the study of mechanisms underlying the development of hypertension. Our fourth and final aim is to testthe hypothesis that individuals who displayed impaired stress-induced pressure natriuresis on initial testingwill display greater increases in blood pressure and related target organ damage than those who displayednormal stress-induced pressure natriuresis. This follow-up study will provide more direct evidence of theclinical significance of impaired stress-induced pressure natriuresis.Relevance to public health: High blood pressure, or hypertension, remains a significant health problem inindustrialized nations. The problem is particularly significant in the African-American population in whom'impaired' sodium regulation plays an important role. The results of this study will help further define theinteractive effects of genetic predisposition and environmental stress on sodium handling in the developmentof hypertension, particularly in overweight African-Americans. The pharmacologic interventions will alsoprovide evidence for effective management of this potentially clinically significant response pattern.
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