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 date||11/1/98 → 10/31/00|
- National Institutes of Health