Angiotensin II Type 1-Receptor Antagonist Candesartan Cilexitil Prevents Left Ventricular Dysfunction in Myocardial Infarcted Rats

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• The purpose of this study was to analyze the effect of the angiotensin II type 1-receptor antagonist candesartan cilexitil on left ventricular systolic and diastolic function and mRNA expression of contractile proteins, collagen, and Ca2+ handling protein in myocardial-infarcted rats. After myocardial infarction, the animals were randomly assigned to candesartan cilexitil-treated or untreated groups (MI). We performed Doppler-echocardiographic examination and measured the hemodynamics at four and twelve weeks after myocardial infarction. Following these measurements, their cardiac mRNA was analyzed. At four weeks in MI, left ventricular end-diastolic dimension increased (Control, 6.2±0.6 mm; MI, 8.7±0.6 mm; P<0.01), fractional shortening decreased (Control, 41±5%; MI, 16±3%; P<0.01) and E wave deceleration rate increased (Control, 14.3±2.0 m/sec2; MI, 23.3±2.3 m/sec2; P<0.01). Candesartan cilexitil significantly prevented these changes. The mRNA expressions of β-myosin heavy chain, α-skeletal actin, atrial natriuretic peptide, and collagens I and III in the non-infarcted left ventricle and right ventricle were increased at four weeks and were significantly suppressed by treatment with candesartan cilexitil. At four weeks, Na+-Ca2+ exchanger mRNA expression was increased, and candesartan cilexitil suppressed this increase. At twelve weeks, sarcoplasmic reticulum Ca2+-ATPase mRNA expression in the infarcted region including the adjacent non-infarcted left ventricle and right ventricle were decreased and candesartan cilexitil restored it to the control level. Candesartan cilexitil prevented the systolic and diastolic dysfunction and abnormal cardiac mRNA expression in myocardial-infarcted rats.

• 社団法人 日本薬理学会の論文

著者

• Iwao H

  Department Of Pharmacology Osaka City University Medical School

• Yamaguchi Junichi

  Division Of Cardiology Saitama Prefecture Cardiovascular And Respiratory Center

• IWAO Hiroshi

  Department of Pharmacology, Osaka City University School of Medicine

• Shimada Kenei

  大阪掖済会病院 循環器科

• Shimada Kenei

  ベルランド総合病院 循環器内科

• Kim-mitsuyama Shokei

  熊本大学 医学教育部生体機能薬理学

• Kim-mitsuyama Shokei

  大阪市立大学 医学研究科薬理学

• Shimada Kenei

  Department Of Cardivascular Medicine Osaka Ekisaikai Hospital

• Nakanishi Koji

  Department Of Cardiovascular Surgery Tsukazaki Memorial Hospital

• Ozaki Takeshi

  Bell land general hospital

• Yoshiyama Minoru

  First Department of Internal Medicine Osaka City University Medical School

• Takeuchi Kazuhide

  First Department of Internal Medicine Osaka City University Medical School

• Yoshikawa Junichi

  First Department of Internal Medicine Osaka City University Medical School

• Sato Hiroshi

  Department Of Pharmacology Osaka City University Medical School

• Sato Hiroshi

  大阪大学 医学系研究科循環器内科学

• Iwao Hiroshi

  大阪市立大学 医分子生体医学

• Takeuchi Kazuhide

  大阪市立大学 医学研究科循環器病態内科学

• Takeuchi Kazuhide

  The First Department Of Internal Medicine Osaka City University Medical School

• Muro Takashi

  Actmce1

• Muro Takashi

  大阪市立大学 医学部循環器病態内科学

• Muro Takashi

  大阪市立大学 医研究 循環器病態内科

• Hirasawa Akira

  京都大学 薬学研究科ゲノム創薬科学

• Sakata Konomi

  Actmce1

• Hanatai Akihisa

  First Department Of Internal Medicine Osaka City Unitersity Medical School

• HANATANI Akihisa

  First Department of Internal Medicine, Osaka City Unitersity Medical School

• KIM Shokei

  Department of Pharmacology, Osaka City Unitersity Medical School

• NAKAYAMA Koji

  First Department of Internal Medicine, Osaka City Unitersity Medical School

• OMURA Takashi

  First Department of Internal Medicine, Osaka City Unitersity Medical School

• Kim Shokei

  大阪市立大学 医学部循環器病態内科学

• Katsuma Susumu

  Department Of Genomic Drug Discovery Science Kyoto University Graduate School Of Pharmaceutical Scie

• Iwao Hiroshi

  Department Of Pharmacology Graduate School Of Medicine Osaka City University

• Kim Shokei

  Department Of Pharmacolgy Osaka City Unversity Medical School

• Hanatani Akihisa

  Department Of Internal Medicine And Cardiology Osaka City University Graduate School Of Medicine

• Iwao Hiroshi

  Department Of Cardiovascular Medicine Akita University Graduate School Of Medicine

• Kim Shokei

  Department Of Internal Medicine And Cardiology Osaka City University Medical School

• HANATANI Akihisa

  First Department of Internal Medicine Osaka City University Medical School

• OMURA Takashi

  First Department of Internal Medicine Osaka City University Medical School

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