• Harshfield, Gregory A (PI)

Project: Research project

Project Details


Cardiovascular disease is the leading cause of death among older
individuals. It is clear that impaired regulation of salt plays a role
in this process in many individuals through it's effect on blood
pressure (BP). These individuals are referred to as "salt sensitive"
because their blood pressure changes with sodium intake. The primary
goal of this research is to explore possible mechanisms underlying salt
sensitivity, and how they impact on blood pressure functioning over the
course of a normal day and night. The mechanisms underlying salt
sensitivity have yet to be established, but impaired regulation of the
renin-angiotensin-system (RAS) or the sympathetic nervous system (SNS)
have been reported most often. The results of a recent study suggest
that impaired regulation of these two systems results in different forms
of salt sensitivity which carry different risk because they differ in
the length of time the blood pressure is elevated. The proposed study
will begin to test this hypothesis using the techniques of molecular
biology. The subjects for this study will be 10 African-American
families, including both parents and two children. They will take a 1
gram sodium load for 5 days. Subjects who show different "forms" of
salt sensitivity will be determined by the timing and duration of the
increase in blood pressure induced by salt loading. Groups will include
those individuals who are salt sensitive only during the day, those who
are salt sensitive only during the night, and finally those who are salt
sensitive during both the day and night. The groups will then be
compared to determine difference in the regulation of the RAS and the
SNS. These differences will be further investigated by identifying
genetic polymorphisms associated with the response pattern. Candidate
genes will include those identified in previous studies to be in the
pathway of the regulation of the SNS and RAS. This includes the beta-
adrenergic receptor gene for the SNS and the angiotensin (AGT) and
angiotensin converting enzyme (ACE) genes for the RAS. The hypotheses
are: 1) Daytime salt sensitivity is the result of impaired regulation
of the SNS on a high salt diet in response to the physical and
psychological challenges of the day. This will be associated with a
genetic polymorphism of the beta-adrenergic receptor gene. 2) Nighttime
salt sensitivity is the result of impaired regulation of the RAS on a
high salt diet leading to impairment of fluid homeostasis and BP control
in the supine position. This will be associated with genetic
polymorphisms associated with the RAS. The candidate genes will include
the AGT and ACE genes. 3) Salt sensitivity over the entire 24 hours is
the result of impaired regulation of both systems. It is the result of
genetic polymorphisms associated with both the SNS and the RAS.
Effective start/end date11/1/9810/31/00


  • Medicine(all)


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