Differential expression of nitric oxide synthases (NOS 1‐3) in human skeletal muscle following exercise countermeasure during 12 weeks of bed rest

Abstract

Adaptive changes of major body systems in astronauts during spaceflight can be simulated by strict anti-orthostatic head-down tilt (HDT) bed rest (BR), a ground-based microgravity (microG) model that provides a meaningful opportunity to study atrophy mechanisms and possible countermeasures under controlled experimental conditions. As nitric oxide (NO) signaling is linked to muscle activity, we investigated altered expression of the three major isoforms of nitric oxide synthase (NOS 1-3) at cellular compartments during prolonged HDT BR without (control group) and with resistance exercise interventions (exercise group) using a flywheel ergometer (FWE). Atrophy detected in mixed (fast-slow) m. vastus lateralis (VL) and slow-type m. soleus (SOL) myofiber Types I and II (minus 35-40% of myofiber cross-sectional area) was prevented by FWE training. Concomitant to muscle atrophy, reduced NOS 1 protein and immunostaining was found in VL not in SOL biopsies. In trained VL, NOS 1 protein and immunostaining at myofibers II were significantly increased at the end of BR. Exercise altered NOS 2/caveolin 3 co-immunostaining patterns of subsarcolemmal focal accumulations in VL or SOL myofibers, which suggests reorganization of sarcolemmal microdomains. In trained VL, increased capillary-to-fiber (C/F) ratio and NOS 3 protein content were documented. Activity-linked NO signaling may be widespread in skeletal muscle cellular compartments that may be directly or indirectly impacted by adequate exercise countermeasure protocols to offset the negative effects induced by disuse, immobilization, or extended exposure to microgravity.

Effects of local vibrations on skeletal muscle trophism in elderly people: mechanical, cellular, and molecular events

“…The downregulated constitutive NO synthase (NOS) could be responsible for lowered nitric oxide production and may disrupt nitric oxide signaling in skeletal muscle arterioles, thus impairing vasodilatation in old age (45). Also, in a study of atrophy induction by horizontal bed rest in young males, it was observed that sarcolemmal NOS1 immunofluorescence in the vastus lateralis muscle increased (52). These opposite effects may be explained by age-related variations in muscle conditioning.…”

nNOS regulation of skeletal muscle fatigue and exercise performance

“…Human subjects confined to bed for 90 days were found to experience atrophy of the vastus lateralis (thigh) and soleus (calf) muscles. This atrophy was accompanied by reduced nNOSμ expression and sarcolemmal localization in the vastus lateralis only, suggesting that atrophic regulation of nNOSμ occurs by unidentified muscle-specific mechanisms (Rudnick et al 2004). Thigh muscle size and nNOSμ localization are preserved if bed rest is accompanied by ergometer exercise, which also increases nNOSμ expression above pre-bed rest levels.…”

“…Most human studies suggest that endurance-type exercise leads to increased nNOSμ expression (Frandsen et al 2000;Rudnick et al 2004;McConell et al 2007). For example, endurance-trained athletes have significantly higher (approx.…”

PGC-1α Mediated Muscle Aerobic Adaptations to Exercise, Heat and Cold Exposure

“…NO is synthesised enzymatically by three recognised NO synthase (NOS) isoforms termed; neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS), with nNOS being the primary isoform in the skeletal muscle (Frandsen et al, 1996;Rudnick et al, 2004). nNOS and eNOS are primarily localised in the sarcolemma and vascular endothelium, respectively (Frandsen et al, 1996), although both isoforms also exist in the mitochondria (Frandsen et al, 1996;Kobzik et al, 1994).…”