Nitric oxide and voluntary exercise together promote quadriceps hypertrophy and increase vascular density in female 18-mo-old mice.
Age-related sarcopenia reduces the size, strength, and function of muscle, and the diameter of muscle fibers. It also disrupts the dystrophin-glycoprotein complex, dislocating nitric oxide synthase 1 (NOS-1) and reducing sarcolemmal integrity. This study of quadriceps muscle in 18-mo-old mice showed that NO-donor treatment with isosorbide dinitrate (I) for 6 wk, in combination with voluntary exercise for 3 wk, increased muscle mass by 25% and stimulated cell proliferation. The resulting fiber hypertrophy was accompanied by a lower ratio of protein:DNA, consistent with myogenic-cell hyperplasia. Treatment enhanced the ratio of NOS-1:β-dystroglycan in correlation with fiber diameter, improved sarcolemmal integrity, and increased vascular density after an increase in vascular endothelial growth factor protein at 3 wk. Results demonstrate that age-related muscle refractoriness to exercise can be overcome with NO-donor treatment. Since activation of muscle stem cells and vascular perfusion are limiting factors in the maintenance, regeneration, and growth of aged muscle, results suggest the feasibility of using NO-donor drugs to combat atrophy and muscle ischemia. Improved function and quality of life from the NO-amplified effects of exercise may be useful in aging and other conditions such as disuse, insulin resistance, or microgravity.
Department of Surgery, University of Manitoba, Winnipeg, Manitoba, Canada.
Jeff R S
JR
Leiter
Ritika
R
Upadhaya
Judy E
JE
Anderson
D000375:Aging / Q000187:drug effects / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D005260:Female; D006984:Hypertrophy / Q000378:metabolism; D007150:Immunohistochemistry; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009133:Muscular Atrophy / Q000503:physiopathology / Q000517:prevention & control; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D052097:Quadriceps Muscle / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology*
D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D007548:Isosorbide Dinitrate