Beneficial effects on skeletal muscle of the angiotensin II type 1 receptor blocker irbesartan in experimental heart...

Area of Science:

• Cardiovascular Research
• Skeletal Muscle Physiology
• Cellular Biology

Background:

• Congestive heart failure (CHF) is associated with skeletal muscle atrophy, increased fatigability, and apoptosis.
• Tumor necrosis factor-alpha (TNFalpha) is implicated in myocyte apoptosis in CHF.
• Angiotensin II receptors are potential regulators of apoptosis in CHF-related muscle wasting.

Purpose of the Study:

• To investigate whether angiotensin II receptor blockade can prevent skeletal muscle apoptosis in rats with CHF.
• To evaluate the effects of irbesartan on myocyte apoptosis, muscle atrophy, and related molecular markers.

Main Methods:

• Congestive heart failure (CHF) was induced in rats using monocrotaline.
• Rats with CHF were treated with irbesartan (angiotensin II receptor blocker) or nifedipine.
• Skeletal muscle analysis included myocyte apoptosis, myosin heavy chains (MHC), Bcl-2, caspases, and cross-sectional area.

Main Results:

• Irbesartan treatment significantly reduced myocyte apoptosis and muscle atrophy compared to untreated CHF rats.
• Irbesartan increased Bcl-2 levels and muscle fiber cross-sectional area, restoring MHC patterns towards control levels.
• Nifedipine treatment did not prevent apoptosis or atrophy; angiotensin II levels were elevated in all CHF rats, while TNFalpha decreased only with irbesartan.

Conclusions:

• Angiotensin II receptor blockade protects against apoptosis-dependent skeletal muscle atrophy in CHF.
• The observed protective effects may be mediated, in part, by a reduction in TNFalpha levels.