Angiotensin 1-7 in Obesity Hypertension

Obesity is a major public health concern that greatly increases risk for developing
cardiovascular disease. Importantly, obesity is associated with endothelial dysfunction and
elevated sympathetic tone, vascular and autonomic derangements known to elevate blood
pressure and increase cardiovascular risk. The renin-angiotensin system may explain
cardiovascular complications in obesity. Angiotensin-(1-7) is a beneficial hormone that is
reduced in obesity and restoration of this hormone improves endothelial function and reduces
sympathetic activity in animal models, which may contribute to its blood pressure-lowering
effects. The investigators will test the hypothesis that angiotensin-(1-7) improves
cardiovascular function in humans with obesity hypertension. This hypothesis will be tested
in a randomized, double blind, placebo-controlled crossover study. The investigators will
measure the effects of acute intravenous angiotensin-(1-7) infusion on endothelial-mediated
vasodilation in the brachial and coronary arteries and on blood pressure and muscle
sympathetic nerve activity with direct microneurography recordings in obese hypertensive
humans.

Inclusion Criteria:

- Men and women of all races

- Capable of giving informed consent

- Age 18-60 years

- Body mass index (BMI) between 30-40 kg/m2

- Hypertension defined as two or more seated blood pressure readings >130/80 mmHg or use
of anti-hypertensive medications

- Satisfactory history and physical exam

Exclusion Criteria:

- Age ≤ 17 or ≥ 61 years

- Pregnant or nursing women

- Decisional impairment

- Prisoners

- Alcohol or drug abuse

- Current smokers

- Highly trained athletes

- Subjects with >5% weight change in the past 3 months

- Evidence of type I or type II diabetes (fasting glucose > 126 mg/dL or use of
anti-diabetic medications)

- History of serious cardiovascular disease (e.g. myocardial infarction within 6 months,
symptomatic coronary artery disease, presence of angina pectoris, significant
arrhythmia, congestive heart failure, deep vein thrombosis, pulmonary embolism, second
or third degree heart block, mitral valve stenosis, aortic stenosis, hypertrophic
cardiomyopathy) or cerebrovascular disease (e.g. cerebral hemorrhage, stroke,
transient Ischemic attack).

- History or presence of immunological or hematological disorders

- Impaired hepatic function (AST or ALT levels >2 times upper limit of normal range)

- Impaired renal function (serum creatinine >2.0 mg/dl)

- Anemia

- Treatment with serotonin-norepinephrine reuptake inhibitors (SNRIs) or norepinephrine
transporter (NET) inhibitors

- Treatment with phosphodiesterase-5 inhibitors

- Treatment with anticoagulants (e.g. warfarin)

- Treatment with chronic systemic glucocorticoid therapy (>7 consecutive days in 1
month)

- Treatment with any investigational drug in the 1-month preceding the study

- Inability to give, or withdraw, informed consent