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

Ylva Hellsten, Nora Rufener, Jens Nielsen, Birgitte Høier, Peter Krustrup, Jens Bangsbo

Research output: Contribution to journalJournal articleResearchpeer-review


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.

Original languageEnglish
JournalAmerican Journal of Physiology: Regulatory, Integrative and Comparative Physiology
Issue number3
Pages (from-to)R975-82
Publication statusPublished - 2008
Externally publishedYes



  • Adult
  • Cell Proliferation
  • Endothelial Cells
  • Extracellular Fluid
  • Humans
  • Lactates
  • Leg
  • Male
  • Matrix Metalloproteinase 2
  • Microdialysis
  • Movement
  • Muscle, Skeletal
  • Nitric Oxide Synthase Type III
  • Oxygen Consumption
  • Potassium
  • RNA, Messenger
  • Regional Blood Flow
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vascular Endothelial Growth Factor A
  • Journal Article
  • Research Support, Non-U.S. Gov't

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