title: Systemic administration of L-arginine benefits mdx skeletal muscle function.
abstract: A major consequence of muscular dystrophy is that increased membrane fragility leads to high calcium influx and results in muscle degeneration and myonecrosis. Prior reports have demonstrated that increased nitric oxide production via L-arginine treatment of normal and mdx mice resulted in increased expression of utrophin and increased activation of muscle satellite cells, which could ameliorate the dystrophic pathology. We delivered L-arginine to normal and mdx mice, and examined muscles for any functional changes associated with its administration. Treated mdx muscles were less susceptible to contraction-induced damage and exhibited a rightward shift of the force-frequency relationship. Immunoblotting revealed increases in utrophin and gamma-sarcoglycan in the treated muscles. There was also a decrease in Evans blue dye uptake, indicating a reduction in myonecrosis. However, there was no decrease in serum creatine kinase or the proportion of central nuclei, nor any improvement in specific force. Together, these results show that L-arginine treatment can be beneficial to mdx muscle function, perhaps through a combination of enhanced calcium handling and increased utrophin, thereby decreasing muscle degeneration.
authors.affiliation: Department of Anatomy and Cell Biology, School of Dental Medicine, 441 Levy Building, 240 South 40th Street, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. erbarton@biochem.dental.upenn.edu
authors.forename: Elisabeth R
authors.initials: ER
authors.lastname: Barton
authors.forename: Linda
authors.initials: L
authors.lastname: Morris
authors.forename: Masataka
authors.initials: M
authors.lastname: Kawana
authors.forename: Lawrence T
authors.initials: LT
authors.lastname: Bish
authors.forename: Thierry
authors.initials: T
authors.lastname: Toursel
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000008:administration & dosage*; D015153:Blotting, Western / Q000379:methods; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood; D016189:Dystrophin / Q000378:metabolism; D005070:Evans Blue / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D007150:Immunohistochemistry / Q000379:methods; D007211:Indoles; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D049031:Sarcoglycans / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D049411:Utrophin / Q000378:metabolism; D016596:Vinculin / Q000378:metabolism
chemical_list: D016189:Dystrophin; D007211:Indoles; D009566:Nitrates; D009573:Nitrites; D049031:Sarcoglycans; D049411:Utrophin; D016596:Vinculin; D005070:Evans Blue; C007293:DAPI; D001120:Arginine; D003402:Creatine Kinase; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases