Environmental Stress, Genes and Risk of Hypertension

The renewal application for this project will follow-up the findings of the parent grant and previous studies which suggest: 1) African-Americans have an impaired natriuretic response to stress; 2) this pattern is related to the functioning of the renin-angiotensin-aldosterone system; and 3) is associated with the early development of target organ damage. In addition, these studies 4) indicate increased adiposity contributes to the pattern. Specific Aims 1 and 2 will examine the effects of an angiotensin receptor blocker on the pressure natriuresis response to stress in African-Americans with impaired stress-induced pressure natriuresis, confirming the role of angiotensin II in the response pattern. Furthermore, this effect will be compared in normal weight versus overweight individuals, with a hypothesized greater effect in overweight subjects. Aim 3 will compare the effects of an angiotensin receptor blocker between carriers and noncarriers of a functional polymorphism of the angiotensin II receptor type 1 gene. These results will provide additional evidence for the mechanistic role of angiotensin II and continue our gene/environmental approach to the study of mechanisms underlying the development of hypertension. Our fourth and final aim is to test the hypothesis that individuals who displayed impaired stress-induced pressure natriuresis on initial testing will display greater increases in blood pressure and related target organ damage than those who displayed normal stress-induced pressure natriuresis. This follow-up study will provide more direct evidence of the clinical significance of impaired stress-induced pressure natriuresis.