Angiotensin II induces apoptosis in vivo in skeletal, as well as cardiac, muscle of the rat

• DOI: 10.1113/expphysiol.2005.030908
• Publication Date: 2005-06-30T00:14:26Z
• Authors: Jatin G. Burniston; Amarjit Saini; Lip‐Bun Tan; David F. Goldspink
• Keywords: Male; 03 medical and health sciences; 0302 clinical medicine; Angiotensin II; Muscle Fibers, Skeletal; Animals; Apoptosis; Myocytes, Cardiac; Rats, Wistar; 3. Good health; Rats

Our previous work has established that angiotensin II is cardiotoxic. Here we sought to investigate whether skeletal muscle is similarly susceptible to damage. Male Wistar rats were either given a single subcutaneous injection of angiotensin II (range 1 μg kg−1 to 10 mg kg−1) or only the vehicle and killed 7 h later, or implanted with preconditioned osmotic pumps dispensing 1 mg kg−1 day−1 angiotensin II and killed 9 or 18 h later. Apoptotic (caspase 3 positive) myocytes were counted on cryosections of the heart, soleus, tibialis anterior and diaphragm muscle. Single injections of 100 μg kg−1 to 10 mg kg−1 angiotensin II induced significant (P < 0.05) myocyte apoptosis (per 104 viable myocytes) in the heart and this was heterogeneously distributed, peaking (5.7 ± 0.6; P < 0.05) at a point 6 mm from the apex, i.e. approximately three‐quarters of the way towards the base. The slow‐twitch soleus muscle was also damaged significantly (peak = 2.6 ± 0.4; P < 0.05), while only the administration of 1 mg kg−1 induced significant (P < 0.05) apoptosis in the fast‐twitch tibialis anterior muscle (peak = 1.2 ± 0.3). Infusion of 1 mg kg−1 day−1 angiotensin II induced more myocyte apoptosis than a single bolus administration of the same dose, and in general there was a higher incidence of apoptosis in muscles harvested after 18 than after 9 h. Infusion of 1 mg kg−1 day−1 angiotensin II over 18 h induced significant (P < 0.05) myocyte apoptosis in the heart (3.3 ± 0.4), soleus (3.9 ± 1), tibialis anterior (5.9 ± 0.4) and diaphragm (19.8 ± 5.6) muscle. Depending on the muscle type, angiotensin II induces myocyte apoptosis in skeletal muscle to a similar or greater extent as in cardiac muscle, supporting the hypothesis that angiotensin II is generally toxic to all striated muscles.