Angiotensin II Blockade and Inflammation in Obesity
Status:
Completed
Trial end date:
2011-08-01
Target enrollment:
Participant gender:
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
Details
Lead Sponsor:
Virginia Polytechnic Institute and State University
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Treatments:
Angiotensin II Angiotensinogen Olmesartan Olmesartan Medoxomil