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Heart and Vessels

, Volume 16, Issue 1, pp 12–19 | Cite as

Inhibition of nitric oxide synthesis increases apoptotic cardiomyocyte death and myocardial angiotensin-converting enzyme gene expression in ischemia/reperfusion-injured myocardium of rats

  • T.-J. Youn
  • C.-H. Kim
  • H.-J. Kang
  • D.-W. Kim
  • M.-C. Cho
  • C.-H. Kim
  • B.-H. Oh
  • M.-M. Lee
  • Y.-B. Park
ORIGINAL ARTICLE

Abstract

Cardiomyocyte apoptosis is an important pathogenic mechanism in myocardial ischemia/reperfusion (I/R) injury. It has been shown that nitric oxide (NO) and the renin–angiotensin system (RAS) are closely related, and both systems regulate apoptotic cell death. However, the effects of NO modulation on myocardial apoptotic cell death and changes in the RAS in the I/R-injured myocardium have not been studied. Female Sprague–Dawley rats were randomized into three groups: NO synthesis inhibitor, NG-nitro-l-arginine-methyl ester (l-NAME, 10 mg/kg); NO precursor, l-arginine (540 mg/kg); and vehicle. The rats were then subjected to 45 min coronary occlusion followed by 4 h reperfusion. The TdT-mediated in situ nick and labeling (TUNEL) indices were 39.9% ± 0.8% at the border and 30.9% ± 1.2% at the center of the I/R area in the vehicle group. L-NAME administration significantly increased these TUNEL-positive cells to 45.3% ± 1.9% and 37.9% ± 1.3%, respectively (P < 0.05 each). L-arginine administration reduced the TUNEL index at the border zone with marginal significance (P = 0.08 vs vehicle group). I/R injury significantly reduced the angiotensin-converting enzyme (ACE) mRNA expression in the left (ventricular) free wall of vehicle group rats. However, ACE mRNA expression was 1.9 times greater in the L-NAME group than that in the vehicle group (P < 0.05). This study showed that the inhibition of NO synthesis increased apoptotic cardiomyocyte death and local ACE mRNA expression in the I/R-injured myocardium. Our observations indicate that NO, ACE, and apoptotic cardiomyocyte death are related to each other during I/R injury.

Key words Myocardium Apoptosis Nitric oxide Angiotensin-converting enzyme Ischemia/reperfusion 

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Copyright information

© Springer-Verlag Tokyo 2001

Authors and Affiliations

  • T.-J. Youn
    • 2
  • C.-H. Kim
    • 1
  • H.-J. Kang
    • 1
  • D.-W. Kim
    • 2
  • M.-C. Cho
    • 2
  • C.-H. Kim
    • 1
  • B.-H. Oh
    • 1
  • M.-M. Lee
    • 1
  • Y.-B. Park
    • 1
  1. 1.Division of Cardiology, Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744, Korea Tel. +82-2-760-2226; Fax +82-2-766-8904 e-mail: hyosoo@plaza.snu.ac.krKR
  2. 2.Department of Internal Medicine and Medical Research Institute, Chungbuk National University College of Medicine, Cheongju, KoreaKR

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