Effect of low-voltage electrical stimulation on angiogenic growth factors in ischaemic rat skeletal muscle

Makoto Nagasaka, Masahiro Kohzuki, Toru Fujii, Shinichi Kanno, Takayuki Kawamura, Hiroshi Onodera, Yasuto Itoyama, Masayoshi Ichie, Yasufumi Sato

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


1. Low-voltage electrical stimulation (LVES) in skeletal muscle at a level far below the threshold of muscle contraction has been reported to promote local angiogenesis. However, the mechanism underlying the promotion of local angiogenesis by LVES has not been fully elucidated. In the present study, we evaluated whether angiogenic factors, such as vascular endotherial growth factor (VEGF), hepatocyte growth factor (HGF) and fibroblast growth factor (FGF), as well as other disadvantageous factors, such as inflammation (interleukin (IL)-6) and hypoxia (hypoxia-inducible factor (HIF)-1α), contribute to the local angiogenesis produced by LVES. 2. We completely excised bilateral femoral arteries of male Sprague-Dawley rats. After the operation, electrodes were implanted onto the centre of the fascia of the bilateral tibialis anterior (TA) muscles, tunnelled subcutaneously and exteriorized at the level of the scapulae. The right TA muscles of rats were stimulated continuously at a stimulus frequency of 50 Hz, with a 0.1 V stimulus strength and no interval, for 5 days. The left TA muscles served as controls. 3. We found that both VEGF and HGF protein were significantly increased by LVES in stimulated muscles compared with control. The VEGF level of the LVES group was 89.10 ± 17.19 ng/g, whereas that of the control group was 65.07 ± 12.88 ng/g, as determined by ELISA (P < 0.05). The HGF level of the LVES and control groups was 8.52 ± 1.96 and 5.80 ± 2.14 ng/g, respectively (P < 0.05). In contrast, there was no difference in FGF, IL-6 and HIF-1α between the LVES and control groups. 4. These results suggest that LVES in a hindlimb ischaemia model of rats increases not only VEGF, but also HGF, production, which may be the main mechanism responsible for the angiogenesis produced by LVES.

Original languageEnglish
Pages (from-to)623-627
Number of pages5
JournalClinical and Experimental Pharmacology and Physiology
Issue number7
Publication statusPublished - 2006 Jul


  • Angiogenic factors
  • Electrical stimulation
  • Ischaemia
  • Skeletal muscle

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)


Dive into the research topics of 'Effect of low-voltage electrical stimulation on angiogenic growth factors in ischaemic rat skeletal muscle'. Together they form a unique fingerprint.

Cite this