Received May 14, 2005
Revised June 9, 2005
Accepted after revision June 28, 2005

¹ Liverpool John Moores University
² Liverpool John moores University
³ University of Leeds

^* To whom correspondence should be addressed. E-mail: j.burniston{at}livjm.ac.uk.

	Abstract

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 to 10 mg kg^-1) or only the vehicle and killed 7-h later, or implanted with pre-conditioned osmotic pumps dispensing 1 mg kg^-1 d^-1 angiotensin II and killed 9 h 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 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 d^-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 h than after 9 h. Infusion of 1 mg kg^-1 d^-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.

Key Words: Angiotensin, Histochemistry, Muscle

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