Ghrelin suppresses cardiac sympathetic activity and attenuates early left ventricular remodeling in rats with myocardial infarction

• Project/Area Number: 16590727
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: KISHIMOTO Ichiro National Cardiovascular Center Research Institute, Hypertension Research Laboratory, Chief, 病因部高血圧研究室, 室長 (80312221)
• Co-Investigator(Kenkyū-buntansha): KANGAWA Kenji National Cardiovascular Center Research Institute, Department of Biochemistry, Head, 副所長 (00112417) ; NAGAYA Noritoshi National Cardiovascular Center Research Institute, Department of Regenrative Medicine, Head, 再生医療部, 部長 (60372116)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: Myocardial Infarction / Ghrelin / Cardiac Remodeling / Fibrosis / Hypertrophy

Research Abstract

We assessed the hypothesis that the in vivo administration of Ghrelin might attenuate cardiac late remodeling and prevent heart failure after myocardial infarction (MI). When Ghrelin was administered for 2 weeks in rats with MI, the heart rate was decreased without alteration in arterial pressure. LV enlargement induced by MI was significantly attenuated by ghrelin treatment. Moreover, there was a substantial decrease in LV end-diastolic pressure, and increases in dP/dt max/min in ghrelin-treated MI rats compared to saline-treated MI rats. Ghrelin attenuated an increase in morphometrical collagen volume fraction in the non-infarct region. In conscious rats after MI, acute administration of ghrelin decreased the low-frequency/high-frequency ratio of heart rate variability obtained by a telemetry system. These data suggest the potential usefulness of ghrelin as a new anti-remodeling agent after MI.

Research Products

• [Journal Article] Role of natriuretic peptide receptor guanylyl cyclase-A in myocardial infarction evaluated using genetically engineered mice. (2005)
  • Author(s): 1.Nakanishi M, Saito Y, Kishimoto I, Harada M, Kuwahara K, Takahashi N, Kawakami R, Nakagawa Y, Tanimoto K, Yasuno S, Usami S, Li Y, Adachi Y, Fukamizu A, Garbers DL, Nakao K
  • Journal Title: Hypertension 46(2) Pages: 441-7
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Calcineurin-nuclear factor of activated T cells pathway-dependent cardiac remodeling in mice deficient in guanylyl cyclase A, a receptor for atrial and brain natriuretic peptides. (2005)
  • Author(s): 2.Tokudome T, Horio T, Kishimoto I, Soeki T, Mori K, Kawano Y, Kohno M, Garbers DL, Nakao K, Kangawa K.
  • Journal Title: Circulation 111(23) Pages: 3095-104
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] C-type natriuretic peptide, a novel antifibrotic and antihypertrophic agent, prevents cardiac remodeling after myocardial infarction. (2005)
  • Author(s): 3.Soeki T, Kishimoto J, Okumura H, Tokudome T, Horio T, Mori K, Kangawa K.
  • Journal Title: J Am Coll Cardiol 45(4) Pages: 608-16
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Production and autocrine/paracrine effects of endogenous insulin-like growth factor-1 in rat cardiac fibroblasts. (2005)
  • Author(s): 5.Horio T, Maki T, Kishimoto I, Tokudome T, Okumura H, Yoshihara F, Suga S, Takeo S, Kawano Y, Kangawa K.
  • Journal Title: Regul Pept 124(1-3) Pages: 65-72
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Role of natriuretic peptide receptor guanylyl cyclase-A in myocardial infarction evaluated using genetically engineered mice. (2005)
  • Author(s): Nakanishi M, Saito Y, Kishimoto I, Harada M, Kuwahara K, Takahashi N, Kawakami R, Nakagawa Y, Tanimoto K, Yasuno S, Usami S, Li Y, Adachi Y, Fukamizu A, Garbers DL, Nakao K.
  • Journal Title: Hypertension. Aug 46(2) Pages: 441-447
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Calcineunin-nuclear factor of activated T cells pathway-dependent cardiac remodeling in mice deficient in guanylyl cyclase A, a receptor for atrial and brain natriuretic peptides. (2005)
  • Author(s): Tokudome T, Horio T, Kishimoto I, Soeki T, Mori K, Kawano Y, Kohno M, Garbers DL, Nakao K, Kangawa K.
  • Journal Title: Circulation. Jun 14 111(23) Pages: 3095-3104
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] C-type natriuretic peptide, a novel antifibrotic and antihypertrophic agent, prevents cardiac remodeling after myocardial infarction. (2005)
  • Author(s): Soeki T, Kishimoto I, Okumura H, Tokudome T, Horio T, Mori K, Kangawa K.
  • Journal Title: J Am Coll Cardiol. Feb 15 45(4) Pages: 608-616
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Production and autocrine/paracrine effects of endogenous insulin-like growth factor-1 in rat cardiac fibroblasts. (2005)
  • Author(s): Horio T, Maki T, Kishimoto I, Tokudome T, Okumura H, Yoshihara F, Suga S, Takeo S, Kawano Y, Kangawa K.
  • Journal Title: Regul Pept. Jan 15 124(1-3) Pages: 65-72
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Role of natriuretic peptide receptor guanylyl cyclase-A in myocardial infarction evaluated using genetically engineered mice. (2005)
  • Author(s): Nakanishi et al.
  • Journal Title: Hypertension 46(2) Pages: 441-447
• [Journal Article] Calcineurin-nuclear factor of activated T cells pathway-dependent cardiac remodeling in mice deficient in guanylyl cyclase A, a receptor for atrial and brain natriuretic peptides. (2005)
  • Author(s): Tokudome et al.
  • Journal Title: Circulation 111(23) Pages: 3095-3104
• [Journal Article] C-type natriuretic peptide, a novel antifibrotic and antihypertrophic agent, prevents cardiac remodeling after myocardial infarction. (2005)
  • Author(s): Soeki T, et al.
  • Journal Title: J.Am.Coll.Cardiol. 45 Pages: 608-616
• [Journal Article] Overexpression of brain natriuretic peptide facilitates neutrophil infiltration and cardiac matrix metalloproteinase-9 expression after acute myocardial infarction. (2004)
  • Author(s): 4.Kawakami R, Saito Y, Kishimoto I, Harada M, Kuwahara K, Takahashi N, Nakagawa Y, Nakanishi M, Tanimoto K, Usami S, Yasuno S, Kinoshita H, Chusho H, Tamura N, Ogawa Y, Nakao K.
  • Journal Title: Circulation 110(21) Pages: 3306-12
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Overexpression of brain natriuretic peptide facilitates neutrophil infiltration and cardiac matrix metalloproteinase-9 expression after acute myocardial infarction. (2004)
  • Author(s): Kawakami R, Saito Y, Kishimoto I, Harada M, Kuwahara K, Takahashi N, Nakagawa Y, Nakanishi M, Tanimoto K, Usami S, Yasuno S, Kinoshita H, Chusho H, Tamura N, Ogawa Y, Nakao K.
  • Journal Title: Circulation, Nov 23 110(21) Pages: 3306-3312
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inhibitory effect of C-type natriuretic peptide (CNP) on cultured cardiac myocyte hypertrophy : interference between CNP and endothelin-1 signaling pathways. (2004)
  • Author(s): Tokudome T, et al.
  • Journal Title: Endocrinology 45 Pages: 2131-2140