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In situ demonstration of angiotensin-dependent and independent pathways for hyperaldosteronism during chronic extracellular fluid volume depletion.

Research Project

Project/Area Number 13670850
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionKansai Medical University

Principal Investigator

TAKAYA Junji  Kansai Medical University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (80247923)

Co-Investigator(Kenkyū-buntansha) NODA-ISGIHAR Neiko  Kansai Medical University, Faculty of Medicine, Instructor, 医学部, 助手 (80333194)
MATSUSAKA Taiji  Tokai University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (50317749)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsaldosteron / Angiotensin II / Potassium / Knockout mouse / Chimeric mouse / losartan / 高血圧 / 腎糸球体
Research Abstract

In wild-type mice, a 2-wk administration of losartan, an angiotensin (Ang) II type 1 (AT1) receptor antagonist, along with dietary sodium restriction, resulted in an elevation of piasma aldosterone greater than that seen with sodium restriction alone (2.75±0.35 vs. 1.38±0.16 ng/ml, P<0.01). Plasma potassium increased in sodium-restricted, losartan-treated mice (6.0 ±0.2 Eqm/liter), while potassium remained unchanged in mice with sodium restriction alone. To study the effect of Ang II on glomerulosa cells that may operate independently of plasma potassium in situ, we used chimeric mice made of cells with or without the intact AT1A gene (Agtrla). When animals were fed a normal diet or chrontcally infused with Ang II, the aldosterone synthase mRNA was detectable only in Agtr1a+/+ but not Agtr1a-/- zona glomerulosa cells. After 2 wk of sodium restriction, plasma aldosterone increased (1.51 ±0.27 ng/ml) and potassium remained on average at 4.5±0.2 mEq/liter, with aldosterone synthase mRNA expressed intensively in Agtr1a+/+, but not detectable in Agtr1a-/- cells. Simultaneous sodium restriction and losartan treatment caused increases in plasma potassium (5.5±0.1 mEq/liter) and aldosterone (1.84±0.38 ng/ml), with both Agtr1a-/- and Agtr1a+/+ cells intensively expressing aldosterone synthase mRNA. Thus, aldosterone production is regulated by Ang II in the adrenal gland during chronic alterations in extracellular fluid volume when plasma potassium is maintained within the normal range. In the light of a previous observation that dietary potassium restriction superimposed on sodium restriction abolished secondary hyperaldosteronism in angiotensinogen null-mutant mice, the present findings demonstrate that when the renin-Ang system is compromised, plasma potassium acts as an effective alternative mechanism for the volume homeostasis through its capacity to induce hyperaldosteronism.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] J Takaya, T Matsusaka, H Katori et al.: "In situ demonstration of angiotensin-dependent and independent pathways for hyperaldosteronism during chronic extracellular fluid volume depletion"Molecular Endocrinology. 15. 2229-2235 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] J Takaya, H Higashino, F Kotera, Y Kobayashi: "Intracellular magnesium of platelets in children with diabetes and obesity"Metabolism. 52. 468-471 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 高屋淳二, 松阪泰二, 香取秀行, 藤中秀彦, 市川家國: "2次性高アルドステロン血症におけるアンジオテンシンIIとカリウムの役割:AT1Aノックアウトキメラマウスによる解析"発達腎研究会誌. 9. 16-19 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takaya J, Matsusaka T, Katori H et al.: "In situ demonstration of angiotensin-dependent and independent pathways for hyperaldosteronism during chronic extracellylar fluid volume depletion."Molecular Endocrinology. 15. 2220-2235 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takaya J, Higashino H, Kotera F, Kobayashi Y.: "Intracellular magnesium of platelets in children with diabetes and obesity."Metabolism. 52. 468-471 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takaya J, Hihashino H, Kotera F, Kobayashi Y: "Intracellular magnesium of platelets in children with diabetes and obesity"Metabolism. 48(In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takaya J, Matsusaka T, Katori H, et al.: "IN situ demonstration of angiotensin-dependent and independent pathways for hyperaldosteronism during chronic extracellular fluid volume depletion"Molecular Endocrinology. 15・12. 2229-2235 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 高屋淳二, 松阪泰二, 香取秀行, 藤中秀彦, 市川家國: "2次性アルドステロン血症におけるアンジオテンシンIIとカリウムの役割:AT1Aノックアウトキメラマウスによる解析"発達腎研究会誌. 9・1. 16-19 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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