Angiotensin II Blockade and Inflammation in Obesity
Condition: Overweight; Obese; Prehypertension; Hypertension
MeSH terms: Prehypertension; Obesity; Overweight; Inflammation
Intervention: Olmesartan medoxomil
Intervention description: Crossover intervention comparing antihypertensive medication to no drug intervention.
Intervention MeSH terms: Olmesartan; Olmesartan Medoxomil
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: angiotensin II; obesity; diabetes

Summary:

      Overweight and obesity, which afflicts ~65% of the U.S. population and more than 1 billion
      people worldwide, increases the risk of developing hypertension. Activation of the renin
      angiotensin system (RAS) is an important mechanism by which obesity leads to hypertension. In
      addition to its vasoconstricting and sodium retaining actions, angiotensin II also has potent
      pro-inflammatory actions including macrophage infiltration and expression of proinflammatory
      cytokines in target tissues. Adipose tissue and skeletal muscle appear to be a key sites for
      the generation of proinflammatory cytokines. Although angiotensin II receptor blockade
      reduces inflammation in many tissues, the effects on adipose tissue and skeletal muscle in
      humans are not clear. Importantly, the chronic low grade inflammatory state that accompanies
      obesity complicates hypertension by contributing to insulin resistance and accelerating
      cardiovascular disease. Therefore, the general aim of the present proposal will be to
      determine the influence of angiotensin II receptor blockade on adipose tissue and skeletal
      muscle inflammation and its relation to improvements in insulin sensitivity, if observed, in
      obese hypertensive humans. To address these aims, 44 obese (BMI>30 kg/m2) hypertensive
      (BP>140 systolic and/or 90 diastolic) individuals (age=50-65 years) will be randomized to
      receive 8 weeks of either the angiotensin II receptor antagonist, olmesartan medoxomil, or no
      treatment in a crossover manner. Subcutaneous adipose tissue and skeletal muscle biopsies
      will be obtained and insulin sensitivity (intravenous glucose tolerance tests) will be
      assessed at baseline and following 8 weeks of each intervention. A two week washout period
      will separate the interventions.
    

Eligibility criteria:

        Inclusion Criteria:

          -  18-75 years of age

          -  Weight stable for previous 6 months (+2.0kg)

          -  Sedentary to recreationally active

          -  Willing to be randomized to treatment or placebo

          -  Verbal and written informed consent

          -  Approved for participation by Medical Director (Jose Rivero, M.D.)

        Exclusion Criteria:

          -  Blood pressure outside stated range

          -  Diabetes or taking diabetes medications

          -  Total cholesterol >6.2 mmol/L; triglycerides >4.5 mmol/L

          -  Past or current ischemic heart disease, stroke, respiratory disease, endocrine or
             metabolic disease, neurological disease, or hematological-oncological disease

          -  Evidence of renal insufficiency; GFR< 60 ml/min*

          -  Medications (including but not limited to antihypertensives, statins or other with
             anti-inflammatory actions) or antioxidant vitamins or supplements

          -  Known allergy or hypersensitivity to olmesartan or any of its components

          -  Pregnant or planning to become pregnant