Myocardial fatty acid metabolism and drug therapy in rats with heart failure.

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 13670750
• 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: Niigata university of Pharmacy and Applied Life Sciences
• Principal Investigator: WATANABE Kenichi Niigata University of Pharmacy and Applied We Sciences, Department of Clinical Pharmacology, Professor, 薬学部・臨床薬理学, 教授 (70175090)
• Co-Investigator(Kenkyū-buntansha): MA Meilei Niigata University of Pharmacy and Applied Life Sciences, Department of Clinical Pharmacology, Lecturer, 薬学部・臨床薬理学, 助手 (20333536)
• Project Period (FY): 2001 – 2002
• Keywords: Heart failure / Angiotensin converting enzyme inhibitor / β-blocker / Myocardial sympathetic denervation / Immuno-deficiency / Angiotensin-II receptor blockade / Ischemic heart disease / Fatty acid metabolism

Research Abstract

Dilated cardiomyopathy is a set of heterogeneous diseases of left ventricular dysfunction of unknown etiology, which has a variety of clinical courses and pathological findings. Long-chain fatty acids are one of the major cardiac energy substrates, so, understanding long-chain fatty acid metabolism may help in elucidating the mechanisms of various heart diseases. Angiotensin(AT)-II receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI) have been shown to reduce morbidity and mortality in patients with heart failure, but their inhibitory actions on AT-I-induced increases in blood pressure in heart failure are not clear. AT-I blocking and cardioprotective properties of the ARB candesartan and ACEI quinapril were studied in a rat model of dilated cardiomyopathy. Metaiodobenzylguanidine(MIBG) is a reliable marker for the detection of cardiac adrenergic neuronal damage in heart failure. The cardioprotective properties of carvedilol, a vasodilating β-adrenoceptor blocking agent, were studied in a rat model of dilated cardiomyopathy. Myocardial long-chain fatty acids metabolism was decreased in rats with heart failure. Although low-dose candesartan can block increases in blood pressure with circulating AT-I same to the extent as high-dose quinapril, it does not confer sufficient protection against injury from the rennin-angiotensin system in heart failure. Carvedilol has beneficial effects and protects cardiac adrenergic neurons in dilated cardiomyopathy.

Research Products

• [Journal Article] Betaxolol Improves Survival and Changes Natriuretic Peptide Expression in Rats with Heart Failure. (2003)
  • Author(s): Watanabe K, Wen Juan, Narasimman G, Ma M, Inoue M, Saito Y, Wahed M, Nakazawa M, Hasegawa G, Naito M, Tachikawa H, Tanabe N, Kodama M, Aizawa Y, Yamamoto T, Yamaguchi K, Takahashi T.
  • Journal Title: J Cardiovascul Pharmacol. 41(Sup-1) Pages: S99-S103
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Comparative Effects of Angiotensin II Receptor Blockade (Candesartan) with ACE Inhibitor (Quinapril) in Rats with Dilated Cardiomyopathy (2003)
  • Author(s): Watanabe K, Wen Juan, Narasimman G, Ma M, Inoue M, Saito Y, Waked M, Nakazawa M, Hasegawa G, Naito M, Tachikawa H, Tanabe N, Kodama M, Aizawa Y, Yamamoto T, Yamaguchi K, Takahashi T.
  • Journal Title: J Cardiovascul Pharmacol. 41(Sup-1) Pages: S93-S97
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Angiotensin II type 1 receptor blocker, valsartan, prevented cardiac fibrosis in rat cardiomyopathy after autoimmune myocarditis. (2003)
  • Author(s): Tachikawa H, Kodama M, Hui L, Yoshida T, Hayashi M, Abe S, Kashimura T, Kato K, Hanawa H, Watanabe K, Nakazawa M, Aizawa Y.
  • Journal Title: J Cardiovascul Pharmacol. 41(Sup-1) Pages: S105-S110
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Improved synthesis of pure [18F] fluoro-compounds for PET studies from bromo-compounds. (2003)
  • Author(s): Takahashi T, Mizuno T, Ido T, Iwata R, Watanabe K.
  • Journal Title: Appl.Radiat.Isot. (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Different gene expression of potassium channels by thyroid hormone and an antithyroid drug between the atrium and ventricle of rats. (2003)
  • Author(s): Ma M, Watanabe K, Watanabe H, Hosokawa Y, Komura S, Aizawa Y, Yamamoto T.
  • Journal Title: Jpn Heart J. 44 Pages: 101-110
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Quinapril inhibits progression of heart failure and fibrosis in rats with dilated cardiomyopathy after myocarditis. (2003)
  • Author(s): Wen Juan, Takazawa M, Watanabe K, Ma M, Wahed M, Hasegawa G, Naito M, Yamamoto T, Fuse K, Kato K, Kodama M, Aizawa Y.
  • Journal Title: Mol Cell Biochem. (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Effects of carvedilol on cardiac function and cardiac adirenergic neuronal damage in rats with dilated cardiomyopathy. (2002)
  • Author(s): Watanabe K, Takahashi T, Nakazawa M, Wahed M, Fuse K, Tanabe N, Kodama M, Aizawa Y, Ashino H, Tazawa S.
  • Journal Title: J Nucl Med. 43(4) Pages: 531-535
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Myocardial Sympathetic Denervation, Fatty Acid Metabolism and Left Ventricular Wall Motion in Vasospastic Angina. (2002)
  • Author(s): Watanabe K, Takahashi T, Miyajima S, Hirokawa Y, Tanabe N, Kato K, Kodama M, Aizawa Y, Tazawa S, Inoue M.
  • Journal Title: J Nucl Med. 43(11) Pages: 1476-1481
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification of cryptic splice site, exon skipping and novel point mutations in type I CD36 deficiency. (2002)
  • Author(s): Hanawa H, Watanabe K, Nakamura, T, Ogawa Y, Toba K, Fuse I, Kodama M, Kato K, Fuse K, Aizawa Y.
  • Journal Title: J Med Genetics 39(4) Pages: 286-291
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Effects of pimobendan on adverse cardiac events and physical activities in patients with mild to moderate chronic heart failure. (2002)
  • Author(s): Kato K, Watenabe K et al.(EPOCH Study Group).
  • Journal Title: Circ J. 66(2) Pages: 149-157
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Difference in CD22 molecules in human B cells and basophils. (2002)
  • Author(s): Toba K, Hanawa H, Fuse I, Sakaue M, Watanabe K, Uesugi Y, Higuchi W, Takahashi M, Aizawa Y.
  • Journal Title: Exp Hematology. 30 Pages: 205-211
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Fenofibrate, a peroxisome proliferator-activated receptor α activator, suppresses experimental autoimmune myocarditis by stimulating the interleukin-10 pathway in rats. (2002)
  • Author(s): Mayuyama S, Kato K, Kodama M, Hirono S, Fuse K, Nakagawa O, Nakazawa M, Miida T, Yamamoto T, Watanabe K Aizawa Y.
  • Journal Title: J Atheroscler Thromb. 9(2) Pages: 87-92
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Protection against autoimmune myocarditis by gene transfer of interleukin-10 by electroporation. (2001)
  • Author(s): Watanabe K, Nakazawa M, Fuse K, Hanawa H, Kodama M, Aizawa Y, Ohnuki T, Gejyo F, Maruyama H, Miyazaki J.
  • Journal Title: Circulation. 104 Pages: 1098-1100
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Bisoprolol improves survival in rats with heart failure. (2001)
  • Author(s): Watanabe K, Ohta Y, Inoue M, Ma M, Wahed M, Nakazawa M, Hasegawa G, Naito M, Fuse K, Ito M, Kato K, Hanawa H, Kodama M, Aizawa Y.
  • Journal Title: J Cardidvascul Pharmacol. 38(Sup-1) Pages: S55-S58
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inhibition of progression of heart failure and expression of TGF-β1 mRNA in rats with heart failure by the ACE inhibitor quinapril. (2001)
  • Author(s): Ma M, Watanabe K, Wahed M, Inoue M, Sekiguchi T, Kouda T, Ohta Y, Nakazawa M, Yoshida Y, Yamamoto T, Hanawa H, Kodama M, Fuse K, Aizawa Y.
  • Journal Title: J Cardiovascul Pharmacol. 38(Sup-1) Pages: S51-S54
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Enhanced expression and production of monocyte chemoattractant protein-1 in myocarditis. (2001)
  • Author(s): Fuse K, Kodama, M, Hanawa H, Okura Y, Ito M, Shiono T, Maruyama S, Hirono S, Kate K, Watanabe K, Aizawa Y.
  • Journal Title: Clin Exp Immunol. 124 Pages: 346-352
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Mechanical alternans in patients with chronic heart failure. (2001)
  • Author(s): Kodama M, Kato K, Hirono S, Okura Y, Hanawa H, Ito M, Fuse K, Shiono T, Watanabe K, Aizawa Y.
  • Journal Title: J Cardiac Failure. 7(2) Pages: 138-145
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Watanabe K et al.: "Myocardial Sympathetic Denervation, Fatty Acid Metabolism and Left Ventricular Wall Motion in Vasospastic Angina"J Nucl Med. 43・11. 1476-1481 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ma M, Watanabe K et al.: "Different gene expression of potassium channels by thyroid hormone and an antithyroid drug between the atrium and ventricle of rats"Jpn Heart J.. 44. 101-110 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Watanabe K et al.: "Effects of carvedilol on cardiac function and cardiac adrenergic neuronal damage in rats with dilated cardiomyopathy"J Nucl Med.. 43(4). 531-535 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Wen Juan, Watanabe K et al.: "Quinapril inhibits progression of heart failure and fibrosis in rats with dilated cardiomyopathy after myocarditis"Mol Cell Biochem. (in press). (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Mayuyama S, Watanabe K et al.: "Fenofibrate, a peroxisome proliferator-activated receptor α activator, suppresses experimental autoimmune myocarditis by stimulating the interleukin-10 pathway in rats"J Atheroscler Thromb.. 9. 87-92 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Watanabe K et al.: "Betaxolol Improves Survival and Changes Natriuretic Peptide Expression in Rats with Heart Failure"J Cardiovascul Pharmacol. 41. S99-S103 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Watanabe K et al.: "Comparative Effects of Angiotensin II Receptor Blockade (Candesartan) with ACE Inhibitor (Quinapril) in Rats with Dilated Cardiomyopathy J Cardiovascul Pharmacol. 2003 ; 41(Sup-1) : S93-S97"J Cardiovascul Pharmacol. 41. S93-S97 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Takahashi T, Watanabe K et al.: "Improved synthesis of pure [18F] fluoro-compounds for PET studies from bromo-compounds"Appl. Radiat. Isot.. (in press). (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tachikawa H, Watanabe K et al.: "Angiotensin II type 1 receptor blocker, valsartan, prevented cardiac fibrosis in rat cardiomyopathy after autoimmune myocarditis"J Cardiovascul Pharmacol. 41. S105-S110 (2003)
  • Description: 「研究成果報告書概要(和文)」より