Vascular Dysfunction in Human Obesity Hypertension: Integrative Role of Sympathetic and Renin-Angiotensin Systems (VANISH study)

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