Effect of exercise training on endothelium dependent microvascular function in hindlimb of diabetic rats

• Project/Area Number: 18K10882
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59020:Sports sciences-related
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: Sonobe Takashi 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (70548289)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 運動 / 糖尿病 / 微小血管 / 血管造影 / EDH / ZFDMラット / Goto-Kakizakiラット / 微小血管造影 / 超音波血流測定 / exercise hyperemia / angiography / 微小血管障害 / Exercise / Angiography / Exercise hyperemia / EDHF

Outline of Final Research Achievements

We hypothesized that downregulation of endothelium-dependent hyperpolarization (EDH) inhibits exercise-induced vasodilation in diabetic patients and causes exercise intolerance. To test this hypothesis, we evaluated peripheral vascular function and blood flow distribution in response to muscle contraction in anesthetized diabetic (ZFDM) rats using X-ray in vivo microangiography and transit-time ultrasonic blood flow measurement.
In ZFDM rats, hindlimb vascular function was impaired in the pre-capillary level arterioles and muscle contraction-induced increase in blood flow was suppressed. KCa channels, which involves in EDH-dependent vasodilation contributed to the impaired blood flow response in diabetes. Low-intensity exercise training improved muscle contraction-induced blood flow response, therefore it was suggested that contribution of KCa channels to vascular function was upregulated by exercise training in diabetic condition.

Academic Significance and Societal Importance of the Research Achievements

本研究では，血管イメージングによる“血管まるごと評価”と，超音波血流測定とを組み合わせることにより，糖尿病による下肢微小血管がどのような機能において障害されているのかを明らかにした．このとき，骨格筋収縮による血管と血流の応答は病態下において異なっており，さらには微小血管の拡張能に関与する内皮依存性過分極の寄与度も血管・血流の調節において異なっていたことから，多角的な評価法の重要性が示された．また運動トレーニングは，糖尿病で減弱する速い血流応答を改善している可能性があり，日常動作における疲労性の軽減に効果的であることが考えられた．

Research Products

• [Presentation] Evaluation of Hindlimb Arteriolar Vasodilation Evoked by Dynamic Muscle Contraction in Goto-Kakizaki Rats Using in vivo X-ray Microangiography (2020)
  • Author(s): Sonobe T, Tsuchimochi H, Pearson JT.
  • Organizer: Experimental Biology
  • Int'l Joint Research
• [Presentation] 糖尿病モデルラットにおける運動誘発性血管拡張応答に対する内皮依存性過分極の寄与 (2019)
  • Author(s): 曽野部 崇, 土持 裕胤, Pearson James.
  • Organizer: 第74回 日本体力医学会
• [Remarks] 糖尿病病態下での運動時血流再分配を調節する因子について
  • URL: http://www.ncvc.go.jp/res/divisions/cardiac_physiology/09-theme02.html