Involvement of oxidative stress on detrusor overactivity

• Project/Area Number: 26861271
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Kochi University
• Principal Investigator: SHIMIZU Shogo 高知大学, 教育研究部医療学系基礎医学部門, 助教 (90721853)
• Research Collaborator: SAITO Motoaki 高知大学, 教育研究部医療学系基礎医学部門, 教授 (60273893) ; SHIMIZU Takahiro 高知大学, 教育研究部医療学系基礎医学部門, 准教授 (00363276) ; HIGASHI Youichirou 高知大学, 教育研究部医療学系基礎医学部門, 助教 (80380062) ; NAKAMURA Kumiko 高知大学, 教育研究部医療学系基礎医学部門, 技術専門職員 (30398052)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: アンジオテンシンⅡ / 排尿 / 排尿筋過活動 / 過活動膀胱 / 活性酸素 / 排尿反射 / 頻尿 / 中枢性 / 脳内活性物質

Outline of Final Research Achievements

We examined the effects of centrally administered angiotensin II (Ang II) on the micturition reflex in urethane anesthetized (1.0 g/kg, intraperitoneally) male rats. In the continuous cystometry, central administration of Ang II but not vehicle dose-dependently shortened the urinary bladder intercontraction interval, without altering the bladder detrusor pressure and blood pressure. Central administration of antagonists of Ang II type 1 (AT1) but not type 2 receptors inhibited the Ang II induced micturition reflex. These data suggest that central administration of Ang II increases urinary frequency by acting on brain AT1 receptors. Moreover, centrally administered NADPH oxidase (Nox) inhibitor apocynin changed interctonraction interval in the rat. These data suggest that central Ang II/AT1 receptor/Nox pathways are involved in the activation of micturition reflex.

Research Products

• [Journal Article] Protective effects of the selective alpha1A-adrenoceptor antagonist silodosin against cyclophosphamide-induced cystitis in rats (2016)
  • Author(s): Liu N, Shimizu S, Shimizu T, Nakamura K, Yamamoto M, Higashi Y, Saito M
  • Journal Title: J Pharmacol Sci Volume: 132 Issue: 1 Pages: 71-77
  • DOI: 10.1016/j.jphs.2016.08.007
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Angiotensin II centrally induces frequent urination by acting on brain angiotensin II type 1 receptors in rats. (2016)
  • Author(s): Kawamoto B, Shimizu S, Shimizu T, Higashi Y, Honda M, Sejima T, Saito M, Takenaka A.
  • Journal Title: Sci. Rep. Volume: 6 Issue: 1 Pages: 22213-22213
  • DOI: 10.1038/srep22213
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A stress-related peptide bombesin centrally induces frequent urination through brain bombesin receptor types 1 and 2 in the rat. (2016)
  • Author(s): Shimizu T, Shimizu S, Higashi Y, Nakamura K, Yoshimura N, Saito M.
  • Journal Title: J. Pharmacol. Exp. Ther. Volume: 356 Issue: 3 Pages: 693-701
  • DOI: 10.1124/jpet.115.230334
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Olmesartan ameliorates urinary dysfUnction in the spontaneously hypertensive rat via recovering bladder blood flow and decreasing oxidative stress (2014)
  • Author(s): Shimizu S, Saito M, Oiwa H, Ohmasa F, Tsounapi P, Oikawa R, Dimitriadis F, Martin TD, Satoh I, Kinoshita Y, Tomita S
  • Journal Title: Neurourology and Urodynamics Volume: 33 Issue: 3 Pages: 350-7
  • DOI: 10.1002/nau.22405
  • Peer Reviewed
• [Journal Article] Central bombesin possibly induces S-nitrosylation of cyclooxygenase-1 in pre-sympathetic neurons of rat hypothalamic paraventricular nucleus (2014)
  • Author(s): Tanaka K, Shimizu T, Higashi Y, Nakamura K, Taniuchi K, Dimitriadis F, Shimizu S, Yokotani K, Saito M.
  • Journal Title: Life Sci. Volume: 100 Issue: 2 Pages: 85-96
  • DOI: 10.1016/j.lfs.2014.01.079
  • Peer Reviewed
• [Journal Article] Possible involvement of brain prostaglandin E2 and prostanoid EP3 receptors in prostaglandin E2 glycerol ester-induced activation of central sympathetic outflow in the rat (2014)
  • Author(s): Shimizu T, Tanaka K, Nakamura K, Taniuchi K, Yawata T, Higashi Y, Ueba T, Dimitriadis F, Shimizu S, Yokotani K, Saito M.
  • Journal Title: Neuropharmacology Volume: 82 Pages: 19-27
  • DOI: 10.1016/j.neuropharm.2014.03.005
  • Peer Reviewed / Open Access
• [Journal Article] Effect of an angiotensin II receptor blocker and a calcium channel blocker on hypertension associated penile dysfunction in a rat model (2014)
  • Author(s): Shimizu S, Tsounapi P, Honda M, Dimitriadis F, Taniuchi K, Shimizu T, Inoue K, Saito M
  • Journal Title: Biomed Res Volume: 35 Pages: 215-221
  • NAID: 130004470870
  • Peer Reviewed / Open Access
• [Journal Article] Angiotensin II acting on brain AT1 receptors induces adrenaline secretion and pressor responses in the rat. (2014)
  • Author(s): Nakamura K, Shimizu T, Yanagita T, Nemoto T, Taniuchi K, Shimizu S, Dimitriadis F, Yawata T, Higashi Y, Ueba T, Saito, M
  • Journal Title: Sci Rep Volume: 4 Issue: 1 Pages: 7248-7248
  • DOI: 10.1038/srep07248
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Effect of alpha1 adrenoceptor antagonist naftopidil on the arginine-vasopressin secretion and urine volume in centrally noradrenaline-administered rats (2016)
  • Author(s): Shimizu S, Shimizu T, Yamamoto M, Higashi Y, Nakamura K, Tsounapi P, Liu N, Honda M, Takenaka A, Saito M
  • Organizer: International Continence Society 2016
  • Place of Presentation: Tokyo International Forum, Tokyo Japan
  • Year and Date: 2016-09-13
  • Int'l Joint Research
• [Presentation] 脳内アンジオテンシンIIは中枢性AT1受容体を介して排尿反射を惹起する (2015)
  • Author(s): 清水翔吾, 川本文弥, 清水孝洋, 東洋一郎, 中村久美子, 新武享朗, 齊藤源顕
  • Organizer: 第68回日本薬理学会西南部会
  • Place of Presentation: 海峡メッセ下関 (山口)
  • Year and Date: 2015-11-21
• [Presentation] Central angiotensin II increased urinary frequency acting on brain AT1 receptors in the rat. (2015)
  • Author(s): Kawamoto B, Shimizu S, Honda M, Higashi Y, Shimizu T, Saito M, Takenaka A
  • Organizer: International Continence Society 45th Annual Meeting
  • Place of Presentation: Palais des Congres, Montreal
  • Year and Date: 2015-10-06
  • Int'l Joint Research