Passive leg movement enhances interstitial VEGF protein, endothelial cell proliferation, and eNOS mRNA content in human skeletal muscle

Abstract

The present study used passive limb movement as an experimental model to study the effect of increased blood flow and passive stretch, without enhanced metabolic demand, in young healthy male subjects. The model used was 90 min of passive movement of the leg leading to a 2.8-fold increase ( P < 0.05) in blood flow without a significant enhancement in oxygen uptake. Muscle interstitial fluid was sampled with microdialysis technique and analyzed for vascular endothelial growth factor (VEGF) protein and for the effect on endothelial cell proliferation. Biopsies obtained from the musculus vastus lateralis were analyzed for mRNA content of VEGF, endothelial nitric oxide synthase (eNOS), and matrix metalloproteinase-2 (MMP-2). The passive leg movement caused an increase ( P < 0.05) in interstitial VEGF protein concentration above rest (73 ± 21 vs. 344 ± 83 pg/ml). Addition of muscle dialysate to cultured endothelial cells revealed that dialysate obtained during leg movement induced a 3.2-fold higher proliferation rate ( P < 0.05) than dialysate obtained at rest. Passive movement also enhanced ( P < 0.05) the eNOS mRNA level fourfold above resting levels. VEGF mRNA and MMP-2 mRNA levels were unaffected. The results show that a session of passive leg movement, elevating blood flow and causing passive stretch, augments the interstitial concentrations of VEGF, the proliferative effect of interstitial fluid, and eNOS mRNA content in muscle tissue. We propose that enhanced blood flow and passive stretch are positive physiological stimulators of factors associated with capillary growth in human muscle.

Limb movement-induced hyperemia has a central hemodynamic component: evidence from a neural blockade study

“…Under both CON and BLK conditions, the increase in pulmonary V O 2 due to passive movement was only 0.04 l/min compared with 0.49 l/min when knee extension was actively performed at 15 W. Similarly, leg V O 2 increased by only 0.02 l/min during passive limb movement compared with 0.32 l/min from baseline to active exercise at 15 W. Therefore, the increases in pulmonary V O 2 and leg V O 2 were only 8 and 6%, respectively, of the total increase compared with active exercise. Previous work using a similar passive exercise protocol reported nearly identical and apparently unavoidable increases in both pulmonary and leg V O 2 (12,13). Thus, while passive movement appears to result in a minor increase in metabolism, the contribution of work performed by the subject was Ͻ6% of the actual V O 2 required to perform active knee extension at 15 W. The increase in pulmonary and leg V O 2 may be due to joint and limb stabilization during passive movement.…”

Impact of body position on central and peripheral hemodynamic contributions to movement-induced hyperemia: implications for rehabilitative medicine

“…However, discrepancies exist regarding the magnitude and duration of movement-induced hyperemia during passive exercise. Alterations in body position may be responsible for these discrepancies since we have reported a transient increase in LBF during supine passive movement (14,22,23), whereas others have reported that the elevated LBF was sustained for the duration of passive movement when performed in the upright seated position (15,16). This concept is supported by central and peripheral hemodynamic differences due to manipulation in body position as rest and during exercise (2,7,10,20,25).…”

“…hemodynamics; blood flow; perfusion pressure PASSIVE MOVEMENT, unlike voluntary exercise, occurs without a marked increase in skeletal muscle metabolism (15,36). By the removal of the increase in metabolism associated with exercise, the independent effect of movement on central and peripheral hemodynamic mechanisms governing exercise hyperemia can be identified and studied.…”

“…This concept is supported by central and peripheral hemodynamic differences due to manipulation in body position as rest and during exercise (2,7,10,20,25). Identifying the potentially body position-dependent mechanisms that maximize the increase in LBF may be of utmost importance for the aforementioned individuals, since passive movement performed for an extended period of time or repeatedly performed over the course of weeks appears to be an angiogenic stimulus (15,16). This adaptation, characterized by enhanced vascular endothelial growth factor, endothelial cell proliferation, and capillary growth (15,16), is likely highly dependent on the magnitude and duration of the stimulus (i.e., LBF).…”

Effect of intensified training on muscle ion kinetics, fatigue development, and repeated short-term performance in endurance-trained cyclists

“…After 30 min of rest in the supine position local anesthesia (1 ml of lidocaine, 20 mg/ml without epinephrine) was administered to the skin and subcutaneous tissue. Three microdialysis probes were inserted in the m. vastus lateralis of each leg in a direction parallel with the muscle fiber orientation (17). Membrane length, outer diameter, and molecular cut-off of the probes (custom made) were 40 mm, 0.22 mm, and 6,000 Da, respectively.…”