The Journal of Physiological Sciences

, Volume 69, Issue 2, pp 317–326 | Cite as

Application of transcutaneous carbon dioxide improves capillary regression of skeletal muscle in hyperglycemia

  • Tomohiro Matsumoto
  • Masayuki Tanaka
  • Takuya Ikeji
  • Noriaki Maeshige
  • Yoshitada Sakai
  • Toshihiro Akisue
  • Hiroyo Kondo
  • Akihiko Ishihara
  • Hidemi FujinoEmail author
Original Paper


The purpose of the present study was to determine the effects of transcutaneous CO2 application on the blood flow and capillary architecture of the soleus muscle in rats with streptozotocin (STZ)-induced hyperglycemia. Wistar rats were randomly divided into four groups: control, control + CO2-treated, STZ-induced hyperglycemia, and STZ-induced hyperglycemia + CO2-treated groups. Blood flow in soleus muscle increased during the transcutaneous CO2 exposure, and continued to increase for 30 min after the treatment. In addition, the transcutaneous CO2 attenuated a decrease in capillary and the expression level of eNOS and VEGF protein, and an increase in the expression level of MDM-2 and TSP-1 protein of soleus muscle due to STZ-induced hyperglycemia. These results indicate that the application of transcutaneous CO2 could improve capillary regression via the change of pro- and anti-angiogenesis factors, which might be induced by an increase in blood flow.


CO2 therapy Diabetes Muscle capillary Blood flow Pro-angiogenesis factors Anti-angiogenesis factors 



The study was supported by Grants-in-Aid for Scientific Research (No. 16H03208) from the Japanese Ministry of Education, Culture, Sports, Science and Technology.

Author contribution

TM, MT, TI, and HF conceived and designed the experiments. TM, MT and TI performed the experiments. MT, TI and HF analyzed the data. MT, NM, YS, TA, HK, AI and HF contributed by providing regents, materials and analysis tools. TM, MT, TI, HK, AI and HF interpreted the data and wrote the paper. All authors approved the final version of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.


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Copyright information

© The Physiological Society of Japan and Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  • Tomohiro Matsumoto
    • 1
  • Masayuki Tanaka
    • 2
  • Takuya Ikeji
    • 1
  • Noriaki Maeshige
    • 1
  • Yoshitada Sakai
    • 3
  • Toshihiro Akisue
    • 1
  • Hiroyo Kondo
    • 4
  • Akihiko Ishihara
    • 5
  • Hidemi Fujino
    • 1
    Email author
  1. 1.Department of Rehabilitation ScienceKobe University Graduate School of Health SciencesKobeJapan
  2. 2.Department of Physical Therapy, Faculty of Human SciencesOsaka University of Human SciencesSettsuJapan
  3. 3.Division of Rehabilitation MedicineKobe University Graduate School of MedicineKobeJapan
  4. 4.Department of Food Science and NutritionNagoya Women’s UniversityNagoyaJapan
  5. 5.Laboratory of Cell Biology and Life Science, Graduate School of Human and Environmental StudiesKyoto UniversityKyoto-shiJapan

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