The long term goal of our research team is to determine the mechanism(s) of salt sensitive hypertension in blacks in order to design and test preventive strategies. For this project we will first measure salt sensitivity in African American (AA) twins to determine if salt sensitivity (SS) is inherited in AA. Those twin pairs that both have a high degree of salt sensitivity will be used to identify families at high fisk for SS. These families will then be tested to see if they also have salt sensitivity and hypertension. Molecular genetic studies will be used to identify the chromosomal subunit(s) responsible for salt sensitive blood pressure. The specific goal of this project is to test for major gene effects for salt sensitivity (SS) in African Americans(AA) using the 3 day Saline-Lasix protocol developed by Grim and Weinberger. AA will be defined by ethnicity, by family pedigree and by selected genetic markers, including mitochondrial DNA. We will accomplish eight specific aims. 1.) To estimate the population distribution of salt sensitivity (SS). This will be done by performing the Saline-Lasix protocol in 100 sets of AA twins. 2.) To use the power of the study of twins to determine if salt sensitivity in AAs is inherited. This will be done by analysis of the SS data collected in 50 MZ and 50 DZ AA twins. 3.) To determine heritability of key potential physiological mediators of SS in AA. The biochemical markers to be examined will include the major systems involved in blood pressure control, in sodium homeostasis and in volume regulation. 4.) To test the mechanism of salt sensitivity by using pharmacological probes to block the renin-angiotensin system, the """"""""calcium channel"""""""" system and the renal reabsorption of sodium. 5.) To analyze candidate genetic markers for their effect on SS. 6.) To use twins classified as salt sensitive to identify families in which major genes may be segregating for salt sensitivity. 7.) To perform segregation analysis in these families for salt sensitive blood pressure and/or markers for salt sensitivity. 8.) To use molecular biological techniques to identify the chromosome subunits that hold the marker(s) for SS. These studies will lead to new ways to determine salt sensitivity in hypertensive patients.
