2002 Fiscal Year Final Research Report Summary
Research on mechanisms for vascular action of adrenomedullin
| Project/Area Number |
10218202
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | University of Tokyo |
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Principal Investigator |
HIRATA Yasunobu Univ. of Tokyo, Medicine, Associate Prof., 医学部附属病院, 講師 (70167609)
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| Co-Investigator(Kenkyū-buntansha) |
SATA Masataka Univ. of Tokyo, Medicine, Lecturer, 医学部附属病院, 助手 (80345214)
SUZUKI Etsu Univ. of Tokyo, Medicine, Lecturer, 医学部附属病院, 助手 (40313134)
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| Project Period (FY) |
1998 – 2002
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| Keywords | adrenomedullin / nitric oxide / endothelium / PI3-K / Akt / vasodilation / knockout mice / ischemia |
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| Research Abstract |
Adrenomedullin is a vasodilatory peptide and major source of circulating adrenomedullin is the vascular wall. The vascular action of adrenomedullin was at first considered to solely due elevated cAMP production, I. e., endothelium-independent vasodilation. However, we found that endothelial denudation substantially reduced the vasodilatory action of adrenomedullin in rodent aortic rings. Furthermore, this adrenomedullin-induced endothelium-dependent vasorelaxation is exerted mostly through activation of the phosphatydil inositol 3-kinase (PI3-K)/Akt pathway. It has been well established that this pathway is involved in various important actions such as anti-apoptosis and tissue protection as well as activation of endothelial nitric oxide synthase (eNOS).
Furthermore, we have reported that expression of the adrenomedullin gene is upregulated by hypoxia. Adrenomedullin abrogates ischemia/reperfusion renal injury. Studies using adrenomedullin gene knockout mice revealed that adrenomedullin plays an important role in vascular formation in embryos. Adrenomedullin transgenic mice were resistant to ischemia/reperfusion renal injury and adrenomedullin knockout mice vice versa. These findings suggest that endogenous adrenomedullin may play an important role as a tissue survival factor.
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Research Products
(14 results)
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[Publications] Hayakawa H, Hirata Y, Kakoki M, Suzuki Y, Nishimatsu H, Nagata D, Suzuki E, Kikuchi K, Nagano T, Kangawa K, Matsuo H, Sugimoto T, Omata M: "Role of nitric oxide-cGMP pathway in adrenomedullin-induced vasodilation in rat"Hypertension. 33. 689-693 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Nagata D, Hirata Y, Suzuki E, Kakoki M, Hayakawa H, Goto A., Ishimitsu I, Minamino N, Ono Y, Kangawa K, Matsuo H, Omata M: "Hypoxia-induced adrenomedullin production in the kidney"Kidney Int. 55. 1259-1267 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Sata M, Kakoki M, Nagata D, Nishimatsu H, Suzuki E, Aoyagi T, Sugiura S, Kojima H, Nagano T, Kangawa K, Matsuo H, Omata M, Nagai R, Hirata Y: "Adrenomedullin and nitric oxide inhibit human endothelial cell apoptosis via a cGMP-independent mechanism"Hypertension. 36. 83-88 (2000)
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[Publications] Shindo T, Kurihara Y, Nishimatsu H, Moriyama N, Kakoki M, Watatani S, Wang Y, Ebihara A, Kuwaki T, Ju K-H, Minamino N, Kangawa K, Ishikawa T, Fukuda M, Kudou A, Akimoto Y, Kawakami H, Imai Y, Imai T, Morita H, Yazaki Y, Nagai R, Hirata Y, Kurihara H: "Vascular abnormalities and elevated blood pressure in mice lacking adrenomedullin gene"Circulation. 104. 1964-1971 (2001)
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[Publications] Nishimatsu H, Suzuki E, Nagata D, Moriyama N, Satonaka H, Walsh K, Sata M, Kangawa K, Matsuo H, Goto A, Kitamura T, Hirata Y: "Adrenomedullin induces endothelium-dependent vasorelaxation via the phosphatidylinositol 3 kinase/akt-dependent pathway in rat aorta"Circ Res. 89. 63-70 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] Nishimatsu H, Hirata Y, Hayakawa H, Nagata D, Satonaka H, Suzuki E, Horie S, Takeuchi T, Ohta N, Homma Y, Minowada S, Nagai R, Kawabe K, Kitamura T: "Effects of intracavemous administration of adrenomedullin on erectile function in rats"Peptides. 22. 1913-1918 (2001)
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[Publications] Nishimatsu H, Hirata Y, Shindo T, Kurihara H, Kakoki M, Nagata D, Hayakawa H, Satonaka H, Sata M, Tojo A, Suzuki E, Kangawa K, Matsuo H, Kitamura T, Nagai R: "Role of endogenous adrenomedullin in the regulation of vascular tone and ischemic renal injury : studies on transgenic/knockout mice of adrenomedullin gene"Circ Res. 90. 657-663 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Nishimatsu H, Hirata Y, Shindo T, Kurihara H, Suzuki E, Sata M, Satonaka H, Takeda R, Nagata D, Kakoki M, Hayakawa H, Kangawa K, Matsuo H, Kitamura T, Nagai R: "Endothelial responses of the aorta from adrenomedullin transgenic mice and knockout mice"Hypertens Res. 26. S79-S84 (2003)
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「研究成果報告書概要(欧文)」より
