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Relationship between blood lipid and endothelin-1 in the diabetic rats

Research Project

Project/Area Number 11670107
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionHoshi University

Principal Investigator

KAMATA Katsuo  Hoshi University, Inst. Med. Chem., Assistant Professor, 医薬品化学研究所, 助教授 (40121496)

Co-Investigator(Kenkyū-buntansha) SUENAGA Hiroshi  Hoshi University, Inst. Med. Chem., Research Assistant, 医薬品化学研究所, 助手 (70277698)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsdiabetes mellitus / streptozotocin / endothelium / endothelin-1 / LDL cholesterol / nitric oxide / EDHF / superoxide anion / インスリン / α受容体 / フルクトース / 血圧
Research Abstract

1) Streptozotocin increases plasma glucose levels. Relationships between the plasma ET-1 level and the levels of other plasma constituents (glucose, cholesterol, and triglyceride) were found in 10-week streptozotocin (STZ)-induced diabetic rats. In contrast, at one week after the STZ injection only plasma ET-1 and glucose levels were elevated, suggesting that the hyperglycemia but not cholesterol might trigger the excess production of ET-1.
2) We investigated the effects of chronic pravastatin treatment on the impaired endothelium-dependent relaxation seen in aortae from established STZ-induced diabetic rats. The enhanced level of malondialdehyde (MDA)-modified LDL seen in STZ-induced diabetic rats was normalized by pravastatin treatment. LDL isolated from diabetic rats, but not those from pravastatin-treated diabetics, showed enhanced the susceptibility to oxidation, but incubation in vitro with pravastatin had no effect on LDL oxidation. Following incubation of control aortae for 6 hr … More with LDL (0.1mg protein mL-1) isolated from diabetic rats, the endothelium-dependent relaxation to acetylcholine was impaired, but LDL isolated from control or pravastatin-treated rats had no such effect. This inhibitory effect of diabetic LDL was prevented by superoxide dismutase (SOD), a superoxide scavenger. These results suggest that pravastatin preserves endothelial function in aortae from STZ-induced diabetic rats without lowering plasma cholesterol, and its effect may be due to decreased LDL oxidation.
3) Aortae from diabetic rats, but not those from high-insulin-treated diabetic rats, showed an impaired endothelium-dependent in response to acetylcholine (ACh) by comparison with untreated controls.In the combined presence of the nitric oxide inhibitor NG-nitro-L-arginine and the cyclo-oxygenase inhibitor indomethacin, NA-induced contractility was significantly greater in aortae from high-insulin-treated diabetic rats than in those from controls or untreated diabetic rats. An increased expression of the mRNA for the α_<1D> and α_<1B> adrenergic receptors was found in aortae from high-insulin-treated diabetic rats. These results demonstrate that in rats with established STZ-induced diabetes, high-insulin treatment prevents the development of an impaired endothelium-dependent relaxation in the aorta, and that such treatment enhances NA-induced contractility. This enhancement may be related to an upregulation in the expression of the mRNA for the α_<1B> or α_<1D> adrenergic receptor that is secondary to the hyperinsulinaemia. Less

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Kobayashi,T.and Kamata,K.: "Effect of insulin treatment on smooth muscle contractility and endothelium-dependent relaxation in rat aortae from established STZ-induced diabetes."Br.J.Pharmacol.. 127. 835-842 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kamata,K.and Hayashi,T.: "Effects of chronic treatment with the spontaneous nitric oxide releaser FK409 on vascular responses in established streptozotocin-induced diabetic rat."Res.Commun.Mol.Pathol.Pharmacol.. 103. 275-294 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kamata,K.and Yamashita,K.: "Insulin resistance and impaired endothelium-dependent renal vasodilatation in fructose-fed hypertensive rats."Res.Commun.Mol.Pathol.Pharmacol.. 103. 195-210 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kamata,K.,Nakamima,M. et al.: "Effects of superoxide dismutase on the acetylcholine-induced relaxation response in cholesterol-fed and streptozotocin-induced mice."J.Smooth Muscle Res.. 35. 33-46 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suenaga,H.and Kamata,K.: "Marked dissociation between intracellular Ca2+ level and contraction on exposure of rat aorta to lysophosphatidylcholine."Eur.J.Pharmacol.. 378. 177-186 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kamata,K.and Mizutani,K.: "Change in angiotensin converting enzyme activity in the renal vascular bed of streptozotocin-induced diabetic rats."Res.Commun.Mol.Pathol.Pharmacol.. 104. 181-192 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Makino,A.and Kamata,K.: "Time-course changes in plasma endothelin-1 and its effects on the mesenteric arterial bed in streptozotocin-induced diabetic rats."Diabetes, Obesity, Metabolism. 1. 47-55 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kamata,K.,Ohychi,K. et al.: "Altered endothelium-dependent and -independent hyperpolarization and endothelium-dependent relaxation in carotid arteries isolated from streptozotocin-induced diabetic rats."Naunyn-Schmiedeberg's Arch.Pharmacol.. 362. 52-59 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Makino,A.,Ohuchi,K. et al.: "Mechanisms underlying the attenuation of endothelium-dependent vasodilatation in the mesenteric arterial bed of the streptozotocin-induced diabetic rats."Br.J.Pharmacol.. 130. 549-556 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kobayashi,T.,Matsumoto,T. et al.: "Mechanisms underlying the chronic pravastatin treatment-induced improvement in the mpaired endothelium-dependent aortic relaxation seen in streptozotocin-induced diabetic rats."Br.J.Pharmacol.. 131. 231-238 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kobayashi, T.and Kamata, K.: "Effect of insulin treatment on smooth muscle contractility and endothelium-dependent relaxation in rat aortae from established STZ-induced diabetes."Br.J.Pharmacol. 127. 835-842 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kamata, K.and Hayashi, T.: "Effects of chronic treatment with the spontaneous nitric oxide releaser FK409 on vascular responses in established streptozotocin-induced diabetic rat."Res.Commun.Mol.Pathol.Pharmacol.. 103. 275-294 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kamata, K.and Yamashita, K.: "Insulin resistance and impaired endothelium-dependent renal vasodilatation in fructose-fed hypertensive rats."Res.Commun.Mol.Pathol.Pharmacol.. 103. 195-210 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kamata, K., Nakajima, M.and Sugiura, M.: "Effects of superoxide dismutase on the acetylcholine-induced relaxation response in cholesterol-fed and streptozotocin-induced mice."J.Smooth muscle Res. 35. 33-46 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suenaga, H.and Kamata, K.: "Marked dissociation between intracellular Ca^<2+> level and contraction on exposure of rat aortato lysophosphatidylcholine."Eur.J.Pharmacol.. 378. 177-186 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kamata, K.and Mizutani, K.: "Change in angiotensin converting enzyme activity in the renal vascular bed of streptozotocin-induced diabetic rats."Res.Commun.Mol.Pathol.Pharmacol.. 104. 181-192 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Makino, A.and Kamata, K.: "Time-course changes in plasmaendothelin-1 and its effects on the mesenteric arterial bed in streptozotocin-induced diabetic rats."Diabetes, Obesity and Metabolism 1. 47-55 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kamata, K., Ohuchi, K.and Kirisawa, H.: "Altered endothelium-dependent and -independent hyperpolarization and endothelium-dependent relaxation in carotid arteries isolated from streptozotocin-induced diabetic rats."Naunyn-shimideberg's Arch.Pharmacol. 362. 52-59 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Makino, A., Ohuchi, K.and Kamata, K.: "Mechanisms underlying the attenuation of endothelium-dependent vasodilatation in the mesenteric arterial bed of the streptozotocin-induced diabetic rats."Br.J.Pharmacol.. 130. 549-556 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kobayashi, T., Matsumoto, T.and Kamata, K.: "Mechanisms underlying the chronic pravastatin treatment-induced improvement in the impaired endothelium-dependent aortic relaxation seen in streptozotocin-induced diabetic rats"Br.J.Pharmacol.. 131. 231-238 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kamata,K.,Nakamima,M. et al.: "Effects of superoxide dismutase on the acetylcholine-induced relaxation rasponse in cholesterol-fed and streptozotocin-induced mice."J.Smooth Muscle REs.. 35. 33-46 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kamata,K.,Ohuchi,K. et al.: "Altered andothelium-dependent and-independent hyperpolarization and endothelium-dependent relaxation in carotid arteries isolated from streptozotocin-induced diabetic rats."Naunyn-Schmiedeberg's Arch.Pharmacol.. 362. 52-59 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Makino,A.,Ohuchi,K. et al.: "Mechanisms underlying the attenuation of endothellum-dependent vasodilatation in the mesenteri c arterial bed of the streptozotocin-induced diabetic rats."Br.J.Pharmacol.. 130. 549-556 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kobayashi,T.,Matsumoto,T. et al.: "Mechanisms underlying the chronic pravastatin treatment-induced improvement in the impaired endothelium-dependent aortic relaxation seen in streptozotocin-induced diabetic rats."Br.J.Pharmacol.. 131. 231-238 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Kobayashi and K.Kamata: "Effect of insulin treatment on smooth muscle contractility and endothelium-dependent relaxation in rats aortae from established STZ-induced diabetes."Br.J.Pharmacol.. 127. 335-842 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Kamata and T.Hayashi: "Effects of chronic treatment with the spontaneous nitric oxide releaser FK409 on vascular responses in established streptozotocin-induced diabetic rat."Res.Commun.Mol.Pathol.Pharmacol.. 103. 275-294 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Kamata and K.Yamashita: "Insulin-resistance and impaired endothelium-dependent renal vasodilatation in fructose-fed hypertensive rats."Res.Commun.Mol.Pathol.Pharmacol.. 103. 195-210 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] A.Makino and K.Kamata: "Time-course changes in plasma endothelin-1 and its effects on the mesenteric arterial bed in streptozotocin-induced diabetic rats."Diabetes,Obesity Metabolism. 1. 1-9 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H.Suenaga and K.Kamata: "Marked dissociation between intracellular C^<a2+> level and contraction on expossure of rat aorta to lysophosphatidylcholine."Eur.J.Pharmacol.. 378. 177-186 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Kamata and K.Mizutani: "Change in angiotensin converting enzyme activity in the renal vascular bed of streptozotocin-induced diabetic rats."Res.Commun.Mol.Pathol.Pharmacol.. 104. 181-192 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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