Dietary Salt in Postural Tachycardia Syndrome

Patients with POTS may not adequately expand their plasma volume in response to a high-sodium (Na+) diet. Mechanisms involved in the regulation of plasma volume, such as the renin-angiotensin-aldosterone system and renal dopamine, may be impaired in POTS and may respond inappropriately to changes in dietary sodium.The purpose of this study is to determine (1) whether a high dietary sodium level appropriately expands plasma volume in POTS; (2) whether plasma renin activity and aldosterone are modified appropriately by changes in dietary sodium in POTS; and (3) whether patients with POTS have improvements in their orthostatic tachycardia and symptoms as a result of a high dietary sodium level.

Study Day 1

* Start 150 milliequivalents (mEq) Na+/day diet (POTS patients as inpatients; healthy control subjects with clinical research center (CRC)- provided outpatient diet)
* Start a 24h urine collection (for Na+, K+, Cr, fractionated catecholamines)
* Blood work
* Blood volume - carbon monoxide rebreathing

Study Day 2

* Complete 24h urine
* Start STUDY DIET (10 mEq Na+/day or 300 mEq Na+/day in a random order) after 3 meals of 150 mEq Na+/day are complete; water ad lib

Study Day 3 - 5

* Continue STUDY DIET; water ad lib
* On Day 5, a 24 hr holter combined ECG monitor will be placed on the subjects.

Study Day 6

* Continue STUDY DIET; water ad lib
* Remove 24h Holter combined ECG monitor and BP monitor from subject
* Start a 24h urine collection (for Na+, K+, Cr, fractionated catecholamines)
* Complete questionnaires
* Nothing by mouth (NPO) after midnight for study next day

Study Day 7 (BIG DAY)

* Awaken early (\~6am) to void (still collecting 24h urine)
* Patient returns to bed, IV catheter inserted
* Posture Study (in morning; between 7-8am ideally)
* Blood pressure and heart rate will be measured while supine and then while standing for up to 30 minutes
* We will draw 3 tablespoons of blood in each body position to measure hormones that regulate blood pressure and blood volume
* Hormones to verify the subject's phase of menstrual cycle
* Serum/plasma aliquots for future analysis
* Subjects will rate symptoms during supine period and at end of stand using Vanderbilt Orthostatic Symptoms Score (VOSS)
* Total Blood Volume (DAXOR)- using injection of iodinated I-131 tagged human serum albumin nominally 25 micro-Ci of radiation blood samples drawn through IV catheter before injection and for \~30 minutes post-injection (total - 25 ml)
* This will be done after supine assessment, but before standing the subject up
* Autonomic Function Test with Cardiac Output and Brief Tilt
* The subject will be tilted up to 60-75 degrees head-up tilt for up to 10 minutes to measure the changes in heart rate and blood pressure and symptoms with upright challenge.
* Blood volume - carbon monoxide rebreathing
* Exercise Capacity Test (in the afternoon) Will estimate maximal oxygen consumption (VO2 max) This test will be conducted on a stationary bicycle. Effort will be gradually increase while expired air is measured during exhaustive physical work.

All procedures are repeated at least a month later with the 2nd level of dietary salt. (Randomized to high or low salt to the first phase, the second phase is the remaining level)

Eligibility Criteria:
Inclusion Criteria:

* Diagnosed with postural tachycardia syndrome by the Vanderbilt Autonomic Dysfunction Center
* Increase in heart rate ≥30 beats/min with position change from supine to standing (10 minutes)
* Chronic symptoms consistent with POTS that are worse when upright and get better with recumbence
* Age between 18-50 years old
* Non-smokers
* Premenopausal patients with POTS and healthy volunteers
* Only female participants are eligible.
* Since 80-90% of POTS patients are female, and there can be differences in measures with the menstrual cycle, including a small number of males might introduce a significant amount of noise.
* Able and willing to provide informed consent

Exclusion Criteria:

* Smokers
* Overt cause for postural tachycardia, i.e., acute dehydration
* Significant cardiovascular, pulmonary, hepatic, or hematological disease by history or screening results
* Pregnant (positive pregnancy test) or breastfeeding
* Hypertension defined as supine resting BP\>145/95 mmHg off medications or needing antihypertensive medication
* Other factors which in the investigator's opinion would prevent the participant from completing the protocol, including poor compliance during previous studies or an unpredictable schedule
* Unable to give informed consent