Angiotensin II Blockade and Inflammation in Obesity

• Status: Completed
• Trial end date: 2011-08-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Virginia Polytechnic Institute and State University
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Angiotensin II; Angiotensinogen; Olmesartan; Olmesartan Medoxomil

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