Anabolic steroids in part reverse glucocorticoid-induced alterations in rat diaphragm.
Animal and clinical studies have shown respiratory muscle dysfunction caused by treatment with glucocorticoids. The present study was designed to investigate whether anabolic steroids are able to antagonize the loss of diaphragm force induced by long-term low-dose methylprednisolone (MP) administration. Male adult rats were randomized to receive saline or MP (0.2 mg . kg-1 .day-1 sc) during 9 mo, with or without nandrolone decanoate (ND; 1 mg . kg-1 . wm -1 im) during the last 3 mo. The approximately 10% reduction in force generation of isolated diaphragm bundles induced by MP was completely abolished by addition of ND. The MP-induced decrease in number of fibers expressing type IIb myosin heavy chains was not reversed by ND. MP slightly reduced type I, IIa, and IIx fiber cross-sectional areas (CSA), but not type IIb fiber CSA. Addition of ND abolished the reduction in IIa and IIx fiber CSA. The MP-induced alterations in glycogenolytic activity and fatty acid oxidation capacity were not reversed by ND. In conclusion, the marked reduction in diaphragm force caused by long-term low-dose MP was completely abolished by addition of ND. ND in part also antagonized the effects of MP on diaphragm morphology but showed no beneficial effects on biochemical changes.
Van Balkom
R H
RH
Department of Pulmonary Diseases, University Hospital Nijmegen, University of Nijmegen, The Netherlands.
Dekhuijzen
P N
PN
Folgering
H T
HT
Veerkamp
J H
JH
Van Moerkerk
H T
HT
Fransen
J A
JA
Van Herwaarden
C L
CL
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000032:analysis; D045930:Anabolic Agents / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002950:Citrate (si)-Synthase / Q000032:analysis; D003964:Diaphragm / Q000187:drug effects* / Q000201:enzymology; D005227:Fatty Acids / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D006003:Glycogen / Q000378:metabolism; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000145:classification / Q000187:drug effects; D018995:Myosin Heavy Chains / Q000145:classification; D009277:Nandrolone / Q000031:analogs & derivatives / Q000494:pharmacology; D000077603:Nandrolone Decanoate; D006005:Phosphorylases / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects
D045930:Anabolic Agents; D005227:Fatty Acids; D005938:Glucocorticoids; D009277:Nandrolone; D006003:Glycogen; D015094:3-Hydroxyacyl CoA Dehydrogenases; D002950:Citrate (si)-Synthase; D006005:Phosphorylases; D018995:Myosin Heavy Chains; D000077603:Nandrolone Decanoate; D008775:Methylprednisolone