2011 Fiscal Year Final Research Report
The therapeutic potentials of ghrelin in cardiovascular diseases-roles of the autonomic nervous system
| Project/Area Number |
21390252
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
KISHIMOTO Ichiro 独立行政法人国立循環器病研究センター, 糖尿病・代謝内科, 医長 (80312221)
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| Co-Investigator(Kenkyū-buntansha) |
TOKUDOME Takeshi 独立行政法人国立循環器病研究センター, 生化学部, 室長 (00443474)
KANGAWA Kenji 独立行政法人国立循環器病研究センター, 研究所, 所長 (00112417)
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| Project Period (FY) |
2009 – 2011
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| Keywords | グレリン / 心臓保護 / 自律神経 |
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| Research Abstract |
Ghrelin is an endogenous ligand for the growth-hormone secretagogues receptor(GHS-R). In addition to its role in the regulation of growth hormone(GH) release, the 28-amino acid peptide also stimulates food intake and induces adiposity. Since GHS-R is detected in the heart and blood vessels, the role of this peptide in the regulation of cardiovascular function has been suggested. Recently, we investigated the effect of daily peripheral ghrelin administration for 2 weeks in a rat model of myocardial infarction and found that ghrelin significantly attenuated cardiac dysfunction and remodeling induced by infarction. Interestingly, chronic administration of ghrelin dramatically suppressed the increase in heart rate and plasma noradrenaline concentration after infarction to the levels similar to sham-operated controls. The effects of ghrelin were accompanied by a decrease in the ratio of the low-to-high frequency spectra of heart rate variability. Moreover, we have also shown that one-shot subcutaneous administration of ghrelin in the very acute phase following infarction effectively rescues cardiac dysfunction/remodeling, prevents arrhythmias and significantly improves mortality. By the direct recoding of cardiac sympathetic nerve activity, it is demonstrated that early ghrelin administration suppresses cardiac sympathetic nerve activity excessively activated after infarction. Surprisingly, one-shot ghrelin administration in the acute phase of myocardial infarction improved cardiac dysfunction and sympathetic hyperactivity in the chronic phase. It is, therefore, suggested that ghrelin is potentially useful as a novel therapy for heart failure, arrhythmia and death in myocardial infarction, with its unique mechanism of action.
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Research Products
(30 results)
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[Journal Article] SPring-8高輝度放射光を用いた小動物の心臓・血管機能の画像解析2010
Author(s)
白井幹康, James Pearson, Daryl Schwenke,曽野部崇,藤井豊,吉本光佐,徳留健,清水壽一郎,寒川賢治,梅谷啓二,八木直人
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Journal Title
循環器研究の進歩
Volume: 30(1)
Pages: 70-82
URL
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[Journal Article] Guanylyl cyclase-A inhibits angiotensin II type 2 receptor-mediated pro-hypertro phic signaling in the heart2009
Author(s)
Li Y, Saito Y, Kuwahara K, Rong X, Kishimoto I, Harada M, Adachi Y, Nakanishi M, Kinoshita H, Horiuchi M, Murray M, Nakao K
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Journal Title
Endocrino logy
Volume: 150(8)
Pages: 3759-3765
DOI
Peer Reviewed
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[Journal Article] Natriuretic peptides enhance the production of adiponectin in human adipo cytes and in patients with chronic heart failure2009
Author(s)
Tsukamoto O, Fujita M, Kato M, Yamazaki S, Asano Y, Ogai A, Okazaki H, Asai M, Nagamachi Y, Maeda N, Shintani Y, Minamino T, Asakura M, Kishimoto I, Funahashi T, Tomoike H, Kitakaze M
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Journal Title
J Am Coll Cardiol
Volume: 53(22)
Pages: 2070-2077
DOI
Peer Reviewed
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[Journal Article] Impaired Recovery of Blood Flow After Hind-Limb Ischemia in Mice Lacking Guanylyl Cyclase-A, a Receptor for Atrial and Brain Natriuretic Peptides2009
Author(s)
Tokudome T, Kishimoto I, Yamahara K, Osaki T, Minamino N, Horio T, Sawai K, Kawano Y, Miyazato M, Sata M, Kohno M, Nakao K, Kangawa K
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Journal Title
Arterioscler Thromb Vasc Biol
Volume: 29(10)
Pages: 1516-1521
DOI
Peer Reviewed
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