This study aims to learn about the effects of continuous positive airway pressure (CPAP) on people with autonomic failure and high blood pressure when lying down (supine hypertension) to determine if it can be used to treat their high blood pressure during the night. CPAP (a widely used treatment for sleep apnea) involves using a machine that blows air into a tube connected to a mask covering the nose, or nose and mouth, to apply a low air pressure in the airways.

The study includes 3-5 days spent in the Vanderbilt Clinical Research Center (CRC): at least one day of screening tests, followed by up to 3 study days. Subjects may be able to participate in daytime and/or overnight studies. The Daytime study consists of 2 study days: one with active CPAP and one with sham CPAP applied for up to 2 hours. The Overnight study consists of 3 study nights: one with active CPAP, one with sham CPAP, both applied for up to 9 hours and one night sleeping with the bed tilted head-up.

The study includes up to 5 days spent in the Vanderbilt University Medical Center, at least one day of screening tests, followed by 2 study days and/or 2 study nights.

Screening tests include a physical examination and history, routine safety laboratory assessments, and autonomic nervous system testing. Medications for high blood pressure will be held for at least 5 half-lives before studies. Subjects may be able to participate in the daytime and/or the overnight studies.

Daytime Study:

Eligible participants will be studied on two separate days in random order: one day with a high CPAP level and one day with a low CPAP level. The active CPAP level will be determined during a CPAP titration trial

On each study day, participants will be instrumented to measure blood pressure, heart rate, hemodynamic parameters, segmental impedance, and markers of cardiovascular risk. A saline lock or IV catheter will be inserted in one of the arm's veins for blood sample collection. Urine will also be collected during studies.

After baseline measurements, active or sham CPAP will then be applied for up to 2 hours. Outcome measurements will be repeated after 1 and 2 hours of CPAP.

Overnight Studies:

Eligible participants will be studied on three separate nights in random order with a active CPAP, sham CPAP, and sleeping in a head-up tilt position. The active CPAP level will be determined during a CPAP titration trial.

On each study night, the intervention (active CPAP, sham CPAP, or head-up tilt position) will be applied for up to 9 hours. Blood pressure, heart rate, hemodynamic parameters, and markers of cardiovascular risk will be assessed throughout the night. Urine will also be collected during this period. On the following morning, participants will have a tilt table test.

Inclusion Criteria:

• Male and female subjects, age 40-80 years, with autonomic failure including pure autonomic failure, multiple system atrophy and Parkinson disease.
• Neurogenic orthostatic hypotension, defined as a ≥20-mmHg decrease in systolic blood pressure within 3 minutes of standing associated with impaired autonomic reflexes determined by autonomic testing in the absence of other identifiable causes.
• Nocturnal supine hypertension (nighttime systolic blood pressure ≥140 mmHg) during the overnight screening for supine hypertension.
• Patients who are willing and able to provide informed consent

Exclusion Criteria:

• Patients with history of recent facial trauma or surgery or intolerance to CPAP or to the CPAP mask.
• Patients who cannot tolerate the medication withdrawal, defined as those who are unable to stand for at least one minute or those with sustained supine blood pressure ≥180/110 mmHg after the medication withdrawal period.
• Bedridden patients or those who are unable to stand due to motor impairment or severe orthostatic hypotension.
• Smokers, patients who are pregnant, or have clinically unstable coronary artery disease, or major cardiovascular or neurological event in the past 6 months; heart failure; and other factors which in the investigator's opinion would prevent the subject from completing the protocol including clinically significant abnormalities in clinical or laboratory testing.

A sham CPAP will be used.