Mechanical loading regulates NOS expression and activity in developing and adult skeletal muscle.
The hypothesis that changes in muscle activation and loading regulate the expression and activity of neuronal nitric oxide (NO) synthase (nNOS) was tested using in vitro and in vivo approaches. Removal of weight bearing from rat hindlimb muscles for 10 days resulted in a significant decrease in nNOS protein and mRNA concentration in soleus muscles, which returned to control concentrations after return to weight bearing. Similarly, the concentration of nNOS in cultured myotubes increased by application of cyclic loading for 2 days. NO release from excised soleus muscles was increased significantly by a single passive stretch of 20% or by submaximal activation at 2 Hz, although the increases were not additive when both stimuli were applied simultaneously. Increased NO release resulting from passive stretch or activation was dependent on the presence of extracellular calcium. Cyclic loading of cultured myotubes also resulted in a significant increase in NO release. Together, these findings show that activity of muscle influences NO production in the short term, by regulating NOS activity, and in the long term, by regulating nNOS expression.
Department of Physiological Science, University of California, Los Angeles, Los Angeles, California 90095, USA.
J G
JG
Tidball
E
E
Lavergne
K S
KS
Lau
M J
MJ
Spencer
J T
JT
Stull
M
M
Wehling
D000375:Aging / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D004558:Electric Stimulation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D019417:Hindlimb Suspension / Q000502:physiology*; D009043:Motor Activity; D009068:Movement; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000201:enzymology / Q000254:growth & development / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical; D013997:Time Factors; D014158:Transcription, Genetic
D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D018995:Myosin Heavy Chains