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REAL TIME ANGIOTENSIN MONITOR FOR SALT SENSITIVITY

$7,003M01FY2009RRNIH

University Of Maryland Baltimore, Baltimore MD

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Abstract

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. There will be no control subjects. 35 healthy subjects, age 18-65 will undergo electrophysiologic measures using ECG, impedance cardiography, EEG, transcranial Doppler sonography, Temperature and movement measurements, heart rate and blood pressure monitoring before and after ingesting an oral salt load a total of 2500 mg of Sodium in tablet form. The low frequency band changes in response to oral salt load will analyzed and correlated with blood pressure changes in response to the oral salt load. Serum angiotensin II, norepinephrine,sodium and potassium levels will also be evaluated before and after oral salt loading. All subjects will follow the same protocol. All research procedures will be explained orally and in written form. All subjects will sign informed consent forms prior to beginning any research procedures. Screening and Evaluation, Day 1 and Day 2 of the study will be performed by Cardiology research staff. Participant will come to GCRC for the Day 3 of study for 4 hours outpatient visit only. On Day 1 subjects will come to Cardiology Clinical Research facility, UMMS for orientation and informed consent. A medical history and baseline blood pressure measurements will be obtained. Subjects will be given instructions for the low salt diet based on guidance from a registered dietician. Subjects will be provided with a log book to record consumed food and fluids, collected urine, and exercise activity. Urine collection containers will also be provided. On Day 2, subjects will follow the salt restricted diet as outlined by the registered dietician. They will maintain food and fluid logs and collect urine samples in provided containers for 12 hours prior to the beginning of the study (i.e. from 9 PM on the night prior) as per the procedure listed prior. Subjects will not come for a laboratory visit on Day 2. Day 3, GCRC visit: subjects will continue to follow the salt restricted diet as outlined by the registered dietician until they come to GCRC at 8-9 AM. Physiologic measurements as listed above will be recorded. An indwelling peripheral intravenous catheter will be placed for blood draw. Approximately 42 minutes of baseline blood pressure and heart rate/low frequency band measurements will be obtained. During the baseline period , subjects will be asked to breathe at a constant rate (0.25 Hz or a complete breath every 4 seconds) for 6 minutes to standardize respiratory variations in heart rate variability;then subjects will perform a simple cognitive task (such as pushing a button when a circle appears on a television screen) for 6 minutes, and then subjects will sit still without any prompts for 6 minutes;one minute will be allowed between each condition for instructions and transition. This cycle will be repeated twice to obtain approximately 42 minutes of baseline data. Blood samples (15 mls or approximately 3 teaspoons at each sampling time) will be drawn at minutes 28 (end of the second paced breathing) and 35 (end of the second cognitive task) for measurements of angiotensin II, norepinephrine, sodium, and potassium. The subjects will then be asked to consume a total of 2500 mg of sodium in tablet form. Approximately 126 minutes of physiological monitoring will then be obtained. Six cycles of paced breathing (6 min), cognitive tasks (6 min), and relaxation without any prompts (6 min) will be repeated to gather the approximately minutes of physiological data post oral salt loading. 15ml of blood (approximately 3 teaspoons) will be collected at minutes 98 (end of the fifth paced breathing after the salt load) and 105 (end of the fifth cognitive task after the salt load) for measurement of serum angiotensin II, norepinephrine, sodium, and potassium levels post oral salt load. Total amount of the blood drawn on day 3 will be approximately 60 mls or 12 teaspoons.

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