Application of transcutaneous carbon dioxide improves capillary regression of skeletal muscle in hyperglycemia
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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.
KeywordsCO2 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.
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.
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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