Elucidation of peripheral mechanism of heat dissipation aimed at preventing heat stroke

• Project/Area Number: 17H04753
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Sports science
• Research Institution: University of Tsukuba
• Principal Investigator: FUJII NAOTO 筑波大学, 体育系, 助教 (00796451)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥25,610,000 (Direct Cost: ¥19,700,000、Indirect Cost: ¥5,910,000); Fiscal Year 2019: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000); Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
• Keywords: 神経ペプチド / マイクロダイアリシス / 熱中症 / 体温 / 地球温暖化 / シグナル伝達 / 熱放散 / トレーニング / 薬理学 / 循環調節

Outline of Final Research Achievements

It remains unknown how heat dissipation (sweating and skin vasodilation) is regulated. In this study, we focused on factors related to ion exchange (nicotine receptor, TRPV4 channel, KATP channel, calcium-dependent chloride ion channel and protease activated receptor), and how these contribute to heat dissipation. From this study, the receptors and ion channels that contribute to the heat dissipation reaction were clarified.

Academic Significance and Societal Importance of the Research Achievements

本研究において，熱放散反応のメカニズムがさらに明らかとなった．これらのデータは，熱中症を防ぐ，具体的方策を構築する上で，極めて重要な知見となる．実際の活用例としては，同定された受容体やイオンチャネルを選択的に活性させ，運動時の熱放散反応を向上させるサプリメント，処方箋，食事法の開発が挙げられる．さらには，同定された受容体やイオンチャネルをトレーニング中に選択的に刺激してそれらの適応を促す，新たなトレーニング方法の開発も挙げられる．これらの新しい熱中症予防方法の確立・普及により，暑熱下での学校体育やスポーツ活動の現場での熱中症の発生件数を大幅に低下させることができると期待される．

Research Products

• [Int'l Joint Research] オタワ大学(カナダ)
• [Journal Article] Nicotinic receptors modulate skin perfusion during normothermia, and have a limited role in skin vasodilatation and sweating during hyperthermia (2019)
  • Author(s): Fujii Naoto、Amano Tatsuro、Kenny Glen P.、Honda Yasushi、Kondo Narihiko、Nishiyasu Takeshi
  • Journal Title: Experimental Physiology Volume: 104 Issue: 12 Pages: 1808-1818
  • DOI: 10.1113/ep088072
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Evidence for TRPV4 channel induced skin vasodilatation through NOS, COX, and KCa channel mechanisms with no effect on sweat rate in humans (2019)
  • Author(s): Fujii Naoto、Kenny Glen P.、Amano Tatsuro、Honda Yasushi、Kondo Narihiko、Nishiyasu Takeshi
  • Journal Title: European Journal of Pharmacology Volume: 858 Pages: 172462-172462
  • DOI: 10.1016/j.ejphar.2019.172462
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Aging attenuates adenosine triphosphate-induced, but not muscarinic and nicotinic, cutaneous vasodilation in men (2018)
  • Author(s): Fujii Naoto、Nishiyasu Takeshi、Sigal Ronald J.、Boulay Pierre、McGarr Gregory W.、Kenny Glen P.
  • Journal Title: Microcirculation Volume: 25 Issue: 5
  • DOI: 10.1111/micc.12462
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The effect of exogenous activation of protease-activated receptor 2 on cutaneous vasodilatation and sweating in young males during rest and exercise in the heat (2018)
  • Author(s): Fujii Naoto、Danquah Mercy O.、Meade Robert D.、Nishiyasu Takeshi、Kenny Glen P.
  • Journal Title: Temperature Volume: 5 Issue: 3 Pages: 257-266
  • DOI: 10.1080/23328940.2018.1506563
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Cyclooxygenase-1 and -2 modulate sweating but not cutaneous vasodilation during exercise in the heat in young men (2018)
  • Author(s): Fujii Naoto、Pastore Olivia L.、McGarr Gregory W.、Meade Robert D.、McNeely Brendan D.、Nishiyasu Takeshi、Kenny Glen P.
  • Journal Title: Physiological Reports Volume: 6 Issue: 17 Pages: e13844-e13844
  • DOI: 10.14814/phy2.13844
  • NAID: 120007133764
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Voltage-gated potassium channels and NOS contribute to a sustained cutaneous vasodilation elicited by local heating in an interactive manner in young adults (2018)
  • Author(s): Fujii Naoto、Halili Lyra、Nishiyasu Takeshi、Kenny Glen P.
  • Journal Title: Microvascular Research Volume: 117 Pages: 22-27
  • DOI: 10.1016/j.mvr.2017.12.001
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Effect of P2 receptor blockade on cutaneous vasodilation during rest and exercise in the heat in young men (2018)
  • Author(s): Fujii Naoto、Meade Robert D.、Louie Jeffrey C.、Akbari Pegah、Boulay Pierre、Sigal Ronald J.、Kenny Glen P.
  • Journal Title: Applied Physiology, Nutrition, and Metabolism Volume: 43 Issue: 3 Pages: 312-315
  • DOI: 10.1139/apnm-2017-0700
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Type 2 diabetes specifically attenuates purinergic skin vasodilatation without affecting muscarinic and nicotinic skin vasodilatation and sweating (2018)
  • Author(s): Fujii Naoto、Meade Robert D.、Brendan McNelly D.、Takeshi Nishiyasu.、Sigal Ronald J.、Kenny Glen P.
  • Journal Title: Experimental Physiology Volume: 103 Issue: 2 Pages: 212-212
  • DOI: 10.1113/ep086694
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Reply to Carter and Green: HSP90: an unappreciated mediator of cutaneous vascular adaptation? (2018)
  • Author(s): Fujii Naoto、Nishiyasu Takeshi、Kenny Glen P.
  • Journal Title: Journal of Applied Physiology Volume: 124 Issue: 2 Pages: 522-522
  • DOI: 10.1152/japplphysiol.01041.2017
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Intradermal administration of atrial natriuretic peptide has no effect on sweating and cutaneous vasodilator responses in young male adults (2017)
  • Author(s): Fujii Naoto、Brendan McNelly D.、Takeshi Nishiyasu.、Kenny Glen P.
  • Journal Title: Temperature Volume: 9 Pages: 406-413
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Heat shock protein 90 contributes to cutaneous vasodilation through activating nitric oxide synthase in young male adults exercising in the heat (2017)
  • Author(s): Fujii Naoto、Zhang Sarah Y.、McNeely Brendan D.、Nishiyasu Takeshi、Kenny Glen P.
  • Journal Title: Journal of Applied Physiology Volume: 123 Issue: 4 Pages: 844-850
  • DOI: 10.1152/japplphysiol.00446.2017
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Na＋/K＋-ATPaseは局所加温による皮膚血管拡張に貢献する (2019)
  • Author(s): ・藤井 直人，天野 達郎，本田 靖，近藤 徳彦，西保 岳
  • Organizer: 第74回日本体力医学会大会
• [Presentation] 発汗調節の末梢メカニズム (2018)
  • Author(s): 藤井 直人
  • Organizer: 第２６回日本発汗学会総会
  • Invited
• [Presentation] ニコチン受容体阻害が安静加温時の 熱放散反応に及ぼす影響 (2018)
  • Author(s): 藤井 直人
  • Organizer: 第73回日本体力医学会大会
• [Presentation] ヒトにおけるin vivoの発汗調節のメカニズム研究 (2017)
  • Author(s): 藤井 直人
  • Organizer: 第31回運動と体温の研究会
  • Invited
• [Presentation] 皮膚血管からみた微小血管機能評価：オレゴン大学とオタワ大学での研究 (2017)
  • Author(s): 藤井 直人
  • Organizer: 日本女子体育大学附属基礎体力研究所セミナー
  • Invited
• [Presentation] Mechanisms underpinning cutaneous vasodilation during exercising in the heat (2017)
  • Author(s): Fujii N
  • Organizer: The 17th International Conference On Environmental Ergonomics
  • Int'l Joint Research / Invited
• [Presentation] KV, KATP, and KCa channels are involved in cutaneous reactive hyperemia but not venous occlusion in-duced cutaneous vasoconstriction in young adults (2017)
  • Author(s): 11.Fujii N, Ichinose M, Nishiyasu T, McNeely BD, Halili L, Kenny GP
  • Organizer: The 17th International Conference On Environmental Ergonomics
  • Int'l Joint Research
• [Presentation] Administration of Prostacyclin Mediates Cutaneous Vasodilation but not Sweating in Young and Older Females: Roles for Nitric oxide and KCa channels. (2017)
  • Author(s): Fujii N, Brendan MD, Kenny GP
  • Organizer: Experimental Biology
  • Int'l Joint Research
• [Presentation] Age-Related Alterations in Cutaneous Vascular and Sweating Responses Depend on Sex and Types of Receptor Agonist (2017)
  • Author(s): 20.Fujii N, Brendan MD, Halili L, Zhang SY, Danquah MO, Kenny GP
  • Organizer: Experimental Biology
  • Int'l Joint Research