Study of Cardiovascular Disease and Obstructive Sleep Apnea

The specific aims of this research project are: 1) Determine if treatment with losartan, an
angiotensin type I receptor (AT1R) antagonist, or allopurinol, a XO inhibitor, normalize
chemoreflex control of sympathetic outflow and ventilation and improve local vascular
regulation and stiffness; and 2) Determine if these interventions reduce the severity of
sleep disordered breathing and lower diurnal blood pressure.

Inclusion Criteria:

- Males and females between ages of 21 and 65 years

- Apnea hypopnea index or respiratory disturbance index greater than or equal to 25
events per hour

- Subjects eligible for CPAP or BiPAP therapy

- Hypertension by clinical history/diagnosis (may be controlled with non- exclusionary
medications) or average blood pressure > 140/90 mm Hg (using last two measurements in
prior 12 months - or 1 prior blood pressure and 1 blood pressure at screening)

Exclusion Criteria:

- If subject not using CPAP, having AHI > 60 events/hour or oxygen saturation ≤ 65%
during sleep

- Presence of clinical CV disease (coronary artery disease, angina, arrhythmias
(subjects with sinus arrhythmias will be reviewed by PI for enrollment), stroke, TIA,
cor pulmonale, etc.), heart failure, bruits, or diabetes mellitus by clinical
diagnosis/history

- Presence of pulmonary disease that results in significant hypoxemia (resting SaO2 <
88%)

- Hypertriglyceridemia (triglycerides >300 mg/dL), diabetes or impaired glucose
tolerance (fasting plasma glucose > 125 mg/dL)

- Patients taking angiotensin converting enzyme inhibitors, angiotensin receptor
antagonists, potassium-sparing diuretics (without accompanying loop/thiazide
diuretic), allopurinol, oxypurinol, febuxostat, amoxicillin, ampicillin, azathioprine
or mercaptopurine.

- Patients with chronic kidney disease (Serum creatinine >1.5 mg/dL) or history of
significant hyperkalemia (Serum potassium > 5.2 mEq/L) with ARB therapy

- Patients with history of angioedema

- Patients with bilateral,modified radical or radical mastectomies

- Patients who have a Serum potassium > 5.0 mEq/L at the screening visit

- Female patients who are pregnant (determined by urine pregnancy test) or
breastfeeding

- Patients with active MRSA or VRE (vancomycin resistant enterococcus) infection

- History of adverse reaction to allopurinol,losartan, or zolpidem**

- Patients who cannot swallow oral capsules

- Patients who are hospitalized or who have been recently hospitalized (last 2 weeks)

- Inability to comply with or complete the protocol or other reasons at the discretion
of the investigators