Vascular Dysfunction in Human Obesity Hypertension

Inclusion Criteria:

- Willing and able to provide written, signed informed consent after the nature of the
study has been explained, and prior to any research-related procedures.

- Systolic blood pressure >/= 130 mmHg and <180 mmHg

- Age is > or = 18 and < or = 79 years of age

- Weight stable (+/- 5 lbs) for the previous 3 months

- Healthy, as determined by health history questionnaire, blood chemistries, 12-lead ECG

- Blood chemistries indicative of normal renal (creatinine <2.0 mg/dl), liver (<3 times
upper limit for ALT, AST), and thyroid function (TSH between 0.4 - 5.0 mU/L)

- If currently receiving treatment with or taking any of the following supplements, be
willing and able to discontinue taking them for 2 weeks prior and throughout the
treatment period: Vitamin C, E or other multivitamins containing vitamin C or E; or
omega-3 fatty acids.

- No history of cardiovascular disease (e.g., heart attack, stroke, heart failure,
valvular heart disease, cardiomyopathy), Type 1 or Type 2 diabetes, or peripheral
arterial disease

- Non-smokers, defined as no history of smoking or no smoking for at least the past 1
year

- Normal resting 12-lead ECG (no evidence of myocardial infarction, left ventricular
hypertrophy, left-bundle branch block, 2nd or 3rd degree AV block, atrial
fibrillation/flutter)

Exclusion Criteria:

- Systolic blood pressure >/=180 mmHg or diastolic blood pressure >110 mmHg

- History of cardiovascular disease such as heart angioplasty/stent or bypass surgery,
myocardial infarction, stroke, heart failure with or without left ventricular ejection
fraction <40%, cardiomyopathy, valvular heart disease, cardiomyopathy, heart
transplantation, Type 2 and Type 1 diabetes

- Smoking or history of smoking within past one year

- History of gastric ulcers, bleeding disorders, dyspepsia, severe gastroesophageal
reflux disease (GERD), or metabolic acidosis

- History of chronic obstructive pulmonary disease (COPD)

- Abnormal resting 12-lead ECG (e.g., evidence of myocardial infarction, left
ventricular hypertrophy, left-bundle branch block, 2nd or 3rd degree AV block, atrial
fibrillation/flutter)

- Serious neurologic disorders including seizures

- History of renal failure, dialysis or kidney transplant

- Serum creatinine > 2.0 mg/dL, or hepatic enzyme (ALT/AST) concentrations > 3 times the
upper limit of normal

- History of HIV infection, hepatic cirrhosis, other preexisting liver disease, or
positive HIV, Hepatitis B or C test at screening.

- Use of any investigational product or investigational medical device within 30 days
prior to screening, or requirement for any investigational agent prior to completion
of all scheduled study assessments.

- History of recent chicken pox, shingles or influenza (ie., risk of Reye's syndrome)

- Recent flu-like symptoms within the past 2 weeks

- Pregnant or breastfeeding at screening, or planning to become pregnant (self or
partner) at any time during the study. A urinary pregnancy test will be done on all
females. If test is positive, the subject will be excluded.

- Women with history of hormone replacement therapy within the past 6 months

- History of rheumatoid arthritis, Grave's disease, systemic lupus erythematosis, and
Wegener's granulomatosis;

- Taking lipid lowering (e.g., statins, niacin), glycemic control (e.g. metformin,
insulin), anticoagulation, anti-seizure, anti-depression or antipsychotic agents

- History of co-morbid condition that would limit life expectancy to < 6 months.

- Taking chronic non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin,
indomethacin, naproxen, acetaminophen (Tylenol), ibuprofen (Advil, Motrin) and not
able or willing to go off of for 2 weeks prior and during the study

- Taking cox-2 inhibitors (Celebrex, Vioxx, etc) or allopurinol (Zyloprim, Lopurin,
Allopurin)

- Taking blood thinners such as coumadin (Warfarin), enoxaparin (Lovenox); clopidogrel
(Plavix); dipyridamole (Persantine); heparin;

- Taking diabetic medications (Metformin, glyburide, insulin, etc.), thiazolidinediones
(Avandia, Rezulin, Actos);

- Taking steroids or biologics : corticosteroids (prednisone); methotrexate, infliximab
(Remicade), etanercept (Enbrel); anakinra;

- Taking thyroid medications such as levothyroxine (Levoxyl, Synthroid, Levoxyl,
Unithroid); Levodopa;

- Taking Phosphodiesterase (PDE) 5 inhibitors (e.g., Viagra®, Cialis®, Levitra®, or
Revatio®); PDE 3 inhibitors (e.g., cilostazol, milrinone, or vesnarinone); lithium

- May participate if no use of the following medications in the 48 hours prior to
experimental visits: naproxen (Aleve), acetaminophen (Tylenol), ibuprofen (Advil,
Motrin), other any non-steroidal anti-inflammatory drugs (NSAIDS)

- Vulnerable populations (prisoners, etc.)

- Any condition that, in the view of the PI, places the subject at high risk of poor
treatment compliance or of not completing the study.

- History of alcohol abuse or >10 alcoholic units per week (1 unit= 1 beer, 1 glass of
wine, 1 mixed cocktail containing 1 oz alcohol)

- On weight loss drugs (e.g., Xenical (orlistat), Meridia (sibutramine), Acutrim
(phenylpropanol-amine), or similar over-the-counter medications) within 3 months of
screening

- Any surgery within 30 days of screening