Essential hypertension (EHYT) is a common, chronic disease contributing to morbidity, mortality, and cost of health care. Established predictors of EHYT account for only a fraction of interindividual blood pressure (BP) variation and provide little insight into its genetic or environmental causes. Forty percent of Caucasian patients with EHYT reportedly fail to modulate renal plasma flow (RPF) and responsiveness of the adrenal gland and renal vasculature to angiotensin II (AII) with changes in sodium (Na+) intake. It has been hypothesized that pleiotropic effects of a single genetic factor account for the abnormalities of non-modulation and that renal effects of this factor that impair Na+ excretion make a substantial contribution to the predisposition to EHYT. The present proposal builds upon the Rochester (MN) Family Heart Study to establish whether renal hemodynamic measures of non-modulation -- i.e., basal renal plasma flow (RPF) and RPF decrease in response to AII infusion under conditions of high Na+ diet -- are intermediate traits which link genetic variation to interindividual differences in BP.
Aim 1 will characterize the distribution of these two renal hemodynamic traits in a population-based sample of 200 unrelated males and 200 unrelated females, ages 20-49.9 years.
Aim 2 will estimate the extent to which each renal hemodynamic trait is associated with established predictors of BP and traits that may modify the relationship between BP and measures of non-modulation -- e.g., age, body size, plasma lipids; erythrocyte sodium-lithium countertransport, and glomerular filtration rate.
Aim 3 will evaluate the ability of each renal hemodynamic trait to predict BP levels (determined by 24 hour ambulatory recording) relative to abilities of other established predictors of BP. Finally, Aim 4 will utilize correlations for these traits between sibling pairs and between spouse pairs to estimate the correlations for these traits between sibling pairs and between spouse pairs to estimate the contributions of shared genetic factors and shared household environmental factors to familial aggregation and interindividual variation of these traits. This will be the first study to characterize the distribution of phenotypic measures of non-modulation among individuals and families in a sample selected from the general Caucasian population. The information obtained will be essential for the design of studies required to evaluate the impact of specific genetic factors on the phenotypes of non-modulation and their contribution to determination of BP.
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