Project: Research project

Project Details


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.
Effective start/end date3/1/922/28/96


  • Medicine(all)