Mechanism of the Cardioprotective Effect of Inhibition of the Renin-Angiotensin System on Ischemia/Reperfusion-Induced Myocardial Injury

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著者

    • WANG Li-Xing
    • Department of Internal Medicine, Fukuoka University School of Medicine
    • YAHIRO Eiji
    • Department of Internal Medicine, Fukuoka University School of Medicine
    • URATA Hidenori
    • Department of Internal Medicine, Fukuoka University School of Medicine
    • ARAKAWA Kikuo
    • Department of Internal Medicine, Fukuoka University School of Medicine
    • SAKU Keijiro
    • Department of Internal Medicine, Fukuoka University School of Medicine

抄録

Inhibition of the renin-angiotensin system (RAS) has been shown to be beneficial in providing cardioprotective effects in humans, but the mechanism of these effects is not well understood. In this study, we examined the effects and mechanism of RAS inhibitors on ischemia/reperfusion (IR)-induced myocardial injury in rats. Rats were randomly divided into five groups and treated with vehicle c, angiotensin converting enzyme inhibitor (ACE-I), angiotensin II type 1 receptor antagonist (AT<SUB>1</SUB>-A), angiotensin II type 2 receptor antagonist (AT<SUB>2</SUB>-A) or ACE-I plus bradykinin B<SUB>2</SUB> antagonist. Ten minutes after administration, the left main coronary artery was ligated for 45 min, and then reperfused for 120 min. IR-induced cardiomyocyte apoptosis was assessed by terminal deoxyribonucleotidyl transferase-mediated Dutp nick-end labeling (TUNEL) assay and confirmed by typical DNA laddering. Mitogen-activated protein kinase, extracellular signal-regulated protein kinase (ERK) and c-<I>Jun</I> NH<SUB>2</SUB>-terminal protein kinase (JNK) activity in the ischemic zone were measured by an <I>in vitro</I> kinase assay. The duration of ventricular tachycardia (VT) during ischemia was reduced by AT<SUB>2</SUB>-A and ACE-I, and increased by AT<SUB>1</SUB>-A and ACE-I+icatibant. ACE-I and AT<SUB>2</SUB>-A reduced apoptosis (by 54% and 53%) and infarct size (by 42% and 41%), while AT<SUB>1</SUB>-A increased apoptosis (by 86%) and infarct size (by 45%). These changes were negatively correlated with the change in ERK activity. The effects of ACE-I on apoptosis and infarct size were abolished by the coadministration of icatibant. Apoptosis was correlated with the occurrence of VT (<I>r</I>=0.837, <I>p</I><0.001). These results suggest that both the accumulation of bradykinin and inhibition of AT<SUB>2</SUB> receptor are cardioprotective against IR injury through the activation of ERK, but not JNK. (Hypertens Res 2001; 24: 179-187)

収録刊行物

  • Hypertension research : clinical and experimental : official journal of the Japanese Society of Hypertension

    Hypertension research : clinical and experimental : official journal of the Japanese Society of Hypertension 24(2), 179-187, 2001-03-01

    The Japanese Society of Hypertension

参考文献:  45件中 1-45件 を表示

被引用文献:  4件中 1-4件 を表示

各種コード

  • NII論文ID(NAID)
    10008742533
  • NII書誌ID(NCID)
    AA10847079
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    09169636
  • データ提供元
    CJP書誌  CJP引用  J-STAGE 
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