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Basic research for the development of the new treatment using endothelin receptor antagonists in cardiovascular diseases

Research Project

Project/Area Number 07557053
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Circulatory organs internal medicine
Research InstitutionUniversity of Tsukuba

Principal Investigator

SUGISHITA Yasuro  University of Tsukuba Institute of Clinical Medicine Professor, 臨床医学系, 教授 (90010131)

Co-Investigator(Kenkyū-buntansha) GOTO Katsutoshi  University of Tsukuba Institute of Basic Medical Sciences Associate Professor, 基礎医学系, 教授 (30012660)
SAKAI Satoshi  University of Tsukuba Institute of Clinical Medicine Research, 臨床医学系, 助手 (30282362)
MIYAUCHI Takashi  University of Tsukuba Institute of Clinical Medicine Assistant Professor, 臨床医学系, 講師 (60222329)
粕谷 善俊  筑波大学, 基礎医学系, 講師 (70221877)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥9,400,000 (Direct Cost: ¥9,400,000)
Fiscal Year 1997: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1996: ¥6,800,000 (Direct Cost: ¥6,800,000)
Keywordscardiovascular diseases / endothelin / endothelin antagonist / heart failure / pulmonary hypertension / pharmacology / エンドセリレ拮抗薬 / 新治療法 / エンドセリン受容体遮断薬
Research Abstract

Endothelin (ET) is an endothelium-derived potent vasoconstrictor peptide. ET is also produced by non-vascular tissues such as the heart, lungs and kidneys. ET has mitogenic activity on vascular smooth muscle cells and induces hypertrophy of cardiac myocytes. In the present work, we studied pathophysiological roles of ET in the animals with various cardiovascular diseases (pulmonary hypertension, heart failure, cardiac hypertrophy, e.t.c.) using molecular biological and biochemical methods. Furthermore, we studied the effects of ET receptor antagonists on the animals with cardiovascular diseases. The present study suggested that endogenous ET is involved in the progression of cardiovascular diseases such as pulmonary hypertension, heart failure and cardiac hypertrophy, and that an ET receptor antagonist may be a useful drug for these theses.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Satoshi, Sakai・et al.: "Inhibition of myocardial endothelin pathway improves long-term survtval in heart failure" Nature. 384. 353-355 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takashi, Miyauchi・et al.: "Vasoconstriction by endothelin-1 in resistance conduit portions of isolated human mesenteric arteries" European Journal of Pharmacology. 303. 193-196 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Satoshi, Sakai・et al.: "Pulmenary hypertension caused by longestive heart failure is markedly ameliorated by chronic application of an endothelin receptor antago" Journal of the American College of Cardilogy. 28. 1580-1588 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Satoshi, Sakai・et al.: "Endogenous endothelin-1 partilipates in the maintenance of cardiac function in rats with congestive heat failure" Circulation. 93. 1214-1222 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takashi, Miyauchi・et al.: "Cloning of hamster preproendothelin-2 cONA and its expression in the heart" Journal of Cardio vuscular Pharmacology. 31. S298-S301 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tsutomu, Kobayshi・et al.: "Down regulation of ET_B receptor,but not ET_p receptor,in congestive lung seconclary to heart failure" Life Sciences. 62. 185-193 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 宮内 卓・酒井 俊・杉下 靖郎: "心不全" 篠山,重威, 697 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 宮内 卓・杉下 靖郎・後藤 勝年: "Annual Review循環器1997" 杉本,恒明・松本,昭彦・杉下,靖郎・門間,和夫, 260 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miyauchi T,Kobayashi T,Yamauchi R,Hoshino T,Sakai S,Kikkawa K,Yabana H,Sugishita Y,Murata S,Goto K.: "Cloning of hamster preproendothelin-1 cDNA and its expression in the heart." Journal of Cardiovascular Pharmacol. 31. S298-S301 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kobayashi T,Miyauchi T,Sakai S,Maeda S,Yamaguchi I,Goto K,Sugishita Y.: "Down-regulation of ET_B receptor, but not ET_A receptor, in congestive lung secondary to heart failure : are marked increases in circulating endothelin-1 partly attributable to decreases in lung ET_B receptor-mediated clearance of endothelin-1?" Life Sciences. 62. 185-193 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sakai S,Miyauchi T,Kobayashi M,Yamaguchi I,Goto K,Sugishita Y.: "Distribution of endothelin-1 in the lung of rats with pulmonary hypertension of different etiology." International Journal of Angiology. 7. 160-164 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kobayashi T,Miyauchi T,Sakai S,Yamaguchi I,Goto K,Sugishita Y.: "Endothelin-converting enzyme and angiotensin-converting enzyme in failing hearts of rats with myocardial infarction." Journal of Cardiovascular Pharmacolog. 31. S417-S420 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sakai S,Miyauchi T,Kobayashi M,Yamaguchi I,Goto K,Sugishita Y.: "Inhibition of myocardial endothelin pathway improves long-term survival in heart failure." Nature. 384. 353-355 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sakai S,Miyauchi T,Sakurai T,Kasuya Y,Ihara M,Yamaguchi I,Goto K,and Sugishita Y.: "Endogenous endothelin-1 participates in the maintenance of cardiac function in rats with congestive heart failure ; Marked increase in endothelin-1 production in the failing heart." Circulation. 93. 1214-1222 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miyauchi T., Tomobe Y,Ishikawa T,Goto K,Sugishita Y.: "Vasoconstriction by endothelin-1 in resistance and conduit portions of isolated human mesenteric arteries." European Journal of Pharmacology. 303. 193-196 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sakai S,Miyauchi T,Sakurai T,Yamaguchi I,Kobayashi M,Goto K,and Sugishita Y.: "Pulmonary hypertension caused by congestive heart failure is markedly ameliorated by chronic application of an endothelin receptor antagonist : increased expression of endothelin-1 mRNA and endothelin-1-like-immunoreactivity in the lung in congestive heart failure in rats." Journal of the American College of Cardiolog. 28. 1580-1588 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Satoshi Sakai, et.al.: "Distribution of endothelin-2 in the lung of rats with pnlmonary hyperteusion of different etiology" International Journal of Angiology. vol.7 No.2. 160-164 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takashi Miyauchi, et.al.: "Cloning of hamster prepro endothelin-1 cDNA and its expression in the heart" Journal of Cardiovascular Pharmacdogy. vol.31. S298-S301 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsutomu Kobayashi, et.al.: "Donm-regul ation of ET_B receptor,but not ET_A receptor,in longestive lung secondary to heast forlure." Life Sciences. vol.62 No.2. 185-193 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Seiji Maeda, et.al.: "Ditference in the change in the time course of plasma andcthetin and endothelin-3 levels after exercise" Life Sciences. vol.61 No.4. 419-425 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 宮内 卓, 酒井 俊, 杉下靖郎: "心不全" 篠山重威, 697 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.Miyauchi,et al.: "Vasc constriction by evdcthelin-2 in Mesistance and condint putions of isolated human nesenterin aitcies" European Journal of Pharmacology. 303. 193-196 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Sakai,et al.: "Inhibition of myocaichal evitothelin pathway inpropes teng-term survival in leart fa-lure." Nature.384. 353-355 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Miyauchi,et al.: "Calcitonia gene-retated peptide(CGRP)in dnes wore poteht vasorelaxations in the resistance portien than in the condnit portion of minantonic as teries in humans." Peptides. 17. 877-879 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Sakai,et al.: "Pulmonary hypeitension caused by angertne heant of:lure is marbedly ameliorated by chronic application of an andsthelin reception antagunis." Journal of the American Colledy of Cardiology. 28. 1580-1588 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Fujita,et al.: "Pregnancy marhedly increares endothelin-1-indned vontraction and charges recepkod snbtuppes in aterine smooth muscle in humans." American Journal of Physiology.(in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Maeda,et al.: "Endothelin-1 production is increased in the circulation of the non-working leg hnt not in working leg in humans." Journal of Applied Physiology. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] 宮内 卓、他: "Annual Review循環器1997" 杉本恒明、他編(中外医学社が出版), 260 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 宮内卓、他: "実験医学:循環研究プロトコール" 矢崎義男 編(中外医学社が出報), 209 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sakai S et. al.: "Endogenous endothelin-1 participates in maintenance of cardiac function in rats with congestive heart failure; Marked increase in endothelin-1 production in the failing heart." Circulation. 印刷中.

    • Related Report
      1995 Annual Research Report
  • [Publications] Miyauchi T et. al.: "Increased endothelin-1 binding sites in the cardiac memranes in rats with chronic heart failure." Jornal of Cardiovascular Pharmacology. 26. S448-S451 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ishikawa S et. al.: "Elevated levels of plasma endothelin-1 in young patients with pulmonary hypertension caused by congenital heart disease are deased after successful surgical repasir." Journal of Thoracic and Cardiovascular Surgery. 110. 271-273 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ishikawa S et. al.: "Influence of pulmonary blood pressure and flow on endothelin-1 production in humans." Jornal of Cardiovascular Pharmacology. 26. S429-S433 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sakai S et. al.: "Altered production of endothelin-1 in the hypertrophied rat heart." Jornal of Cardiovascular Pharmacology. 26. S452-S455 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ishikawa S et. al.: "Plasma endothelin-1 levels after exercise in patients with congenital heart disease." Jornal of Cardiovascular Pharmacology. 26. S491-S493 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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