Effect of heart failure on the regulation of skeletal muscle protein synthesis, breakdown, and apoptosis.
Heart failure is often characterized by skeletal muscle atrophy. The mechanisms underlying muscle wasting, however, are not fully understood. We studied 30 Dahl salt-sensitive rats (10 male, 20 female) fed either a high-salt (HS; n = 15) or a low-salt (LS; n = 15) diet. This strain develops cardiac hypertrophy and failure when fed a HS diet. LS controls were matched to HS rats for gender and duration of diet. Body mass, food intake, and muscle mass and composition were measured. Skeletal muscle protein synthesis was measured by isotope dilution. An additional group of 27 rats (HS, n = 16; LS; n = 11) were assessed for expression of genes regulating protein breakdown and apoptosis. Gastrocnemius and plantaris muscles weighed less (16 and 22%, respectively) in HS than in LS rats (P < 0.01). No differences in soleus or tibialis anterior weights were found. Differences in muscle mass were abolished after data were expressed relative to body size, because HS rats tended (P = 0.094) to weigh less. Lower body mass in HS rats was related to a 16% reduction (P < 0.01) in food intake. No differences in muscle protein or DNA content, the protein-to-DNA ratio, or muscle protein synthesis were found. Finally, no differences in skeletal muscle gene expression were found to suggest increased protein breakdown or apoptosis in HS rats. Our results suggest that muscle wasting in this model of heart failure is not associated with alterations in skeletal muscle metabolism. Instead, muscle atrophy was related to reduced body weight secondary to decreased food intake. These findings argue against the notion that heart failure is characterized by a skeletal muscle myopathy that predisposes to atrophy.
Persinger
Rebecca
R
Department of Medicine, University of Vermont, Burlington, VT 05405, USA.
Janssen-Heininger
Yvonne
Y
Wing
Simon S
SS
Matthews
Dwight E
DE
LeWinter
Martin M
MM
Toth
Michael J
MJ
D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D002303:Cardiac Output, Low / Q000473:pathology / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004435:Eating; D005260:Female; D006614:Hindlimb; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D051381:Rats; D020303:Rats, Inbred Dahl; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage
D009124:Muscle Proteins; D017673:Sodium Chloride, Dietary