This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose a study for the purpose of generating phenotypes for genetic studies of sodium retention, a condition that predisposes to high blood pressure. We focus on three nephron regions, the thick ascending limb where the sodium, potassium, 2 chloride cotransporter operates, the sodium-chloride cotransporter in distal convoluted tubule, and the epithelial sodium channel in the collecting duct. Two hundred unrelated subjects, equal numbers of blacks and whites, males and females, ages 18-35 years, will participate. Subjects will be admitted to the General Clinical Research Center the afternoon before study where they will receive a diet high in sodium. The following morning, one liter of normal saline will be infused over 3 hours. We will assess how subjects excrete (or hold onto) the sodium load (observations will be made over 4 hours). Then subjects will be given a 'loop-diuretic,' furosemide, 10 mg intravenously over 30 minutes, and then observed over a period of 4 hours. One or both parents will give a blood sample for DNA to allow for performing the additional genetic testing of transmission disequilibrium. THis will be an important protocol for developing the phenotypes of sodium retention, and sensitivity of the blood pressure to sodium.
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