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Angiotensin II induces apoptosis in vivo in skeletal, as well as cardiac, muscle of the rat
Author(s) -
Burniston Jatin G.,
Saini Amarjit,
Tan LipBun,
Goldspink David F.
Publication year - 2005
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2005.030908
Subject(s) - angiotensin ii , endocrinology , myocyte , medicine , skeletal muscle , soleus muscle , apoptosis , renin–angiotensin system , chemistry , receptor , blood pressure , biochemistry
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 10 4 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.