Nitric oxide and voluntary exercise together promote quadriceps hypertrophy and increase vascular density in female 18-mo-old mice

Abstract

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.

Age-related alterations in the sarcolemmal environment are attenuated by lifelong caloric restriction and voluntary exercise

“…As indicated by previous studies (Leiter and others 2012; Rice and others 2006) and suggested by our DGC findings, sarcolemmal damage occurs with sedentary, ad libitum aging. To examine this further, we investigated how aging as well as lifelong diet and exercise interventions, on membrane-repair machinery in aged muscle fibers.…”

“…Lieter et al (2012) found that cytoplasmic localization of nNOS is greater in quadriceps of 19.5 month old mice vs. young mice, which could exacerbate proteolysis and atrophy (Suzuki and others 2007). However, 6 weeks of administration of an NO-donor drug and 3 weeks of exercise in 18 month old mice prevented mislocalization of nNOS, concomitant with muscle hypertrophy (Leiter and others 2012). Consistently, loss of sarcolemmal nNOS was causal in skeletal muscle fiber cross-sectional area during disuse (Lawler and others 2014; Suzuki and others 2007).…”

Satellite cell activation and populations on single muscle-fiber cultures from adult zebrafish (Danio rerio)

“…This is seen as particularly important in determining the potential role of SC behavior in defining the capacity for fiber growth by hyperplasia and hypertrophy in zebrafish versus its restriction to fiber hypertrophy in other taxa such as the mouse. In mouse muscle, such interplay affects development and disease progression, the scope of SC heterogeneity, and growth and regenerative capacity (Janke et al, 2013;Leiter and Anderson, 2010;Leiter et al, 2012). Fiber-type specific differences in the NO-HGF-c-met signaling pathway may also be revealed by future studies on fibers, as muscle growth and power are so highly dependent on fast-twitch fibers in fish.…”

Endothelial nitric oxide synthase g894t (rs1799983) gene polymorphism in polish athletes

“…On the other hand, NO exerts several distinct effects on various aspects of skeletal muscle structure and function that could possibly be favourable in strength/power sports, such as excitation-contraction coupling [9], skeletal muscle fiber type conversion (faster-to-slower fiber type) [10], modulation of mitochondrial energy production [11] and glucose metabolism [12]. Further, animal studies provided evidence that nitric oxide may promote exercise-induced muscle hypertrophy [14,[46][47][48], stretch-induced proliferation of myoblasts [49] and prevent muscle atrophy [50]. Indeed, Gomez-Gallego et al [31] proposed that the association of T-786C polymorphism with elite power status may be attributed, at least in part, to the role that NO plays on muscle hypertrophy.…”