title: Aldosterone induces myocyte apoptosis in the heart and skeletal muscles of rats in vivo.
abstract: Over activation of the renin-angiotensin-aldosterone system is known to be cardiotoxic but the potential injurious effects on the skeletal musculature have not been investigated. Male Wistar rats were given subcutaneous injections of aldosterone (1 microg-10 mg kg-1) and killed 7 h later, or continuous infusion (1 mg kg-1 d-1) and killed 48 h later. The role of the mineralocorticoid receptor in mediating aldosterone-induced apoptosis in vivo was investigated using spironolactone (200 mg kg-1). The number of apoptotic (caspase 3 positive) myocytes was counted on cryosections of the heart, soleus and Tibialis Anterior muscles. Injections of aldosterone induced significant (P<0.05) cardiomyocyte apoptosis (peak=2.46+/-0.6 per 10(4) viable myocytes) over the range of 100 microg-10 mg kg-1, whereas only administration of 1 mg kg-1 induced significant (P<0.05) apoptosis (2.47+/-0.8 per 10(4) viable myocytes) in the soleus muscle. In contrast, no apoptosis was detected in the striated muscles after administration of only the vehicle. Infusion of aldosterone induced less apoptosis than the same dose (1 mg kg-1) given as a single injection. Prior administration of spironolactone significantly (P<0.05) protected the heart (90%) and soleus muscle (79%) against the apoptosis induced by a single injection of 1 mg kg-1 aldosterone. These data confirm a myotoxic effect of aldosterone on the heart and provide the first description of aldosterone-induced myocyte apoptosis in skeletal muscle. High circulating levels of aldosterone are clearly capable of damaging all types of striated muscle and this may lend support to the concept that heart failure is a generalised, rather than cardiac-specific, myopathy.
authors.affiliation: Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Webster Street, Liverpool L3 2ET, UK. j.burniston@livjm.ac.uk
authors.forename: Jatin G
authors.initials: JG
authors.lastname: Burniston
authors.forename: Amarjit
authors.initials: A
authors.lastname: Saini
authors.forename: Lip-Bun
authors.initials: LB
authors.lastname: Tan
authors.forename: David F
authors.initials: DF
authors.lastname: Goldspink
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000451:Mineralocorticoid Receptor Antagonists; D032342:Muscle Cells / Q000166:cytology* / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013148:Spironolactone / Q000494:pharmacology
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone