Basic Research in Cardiology

, Volume 96, Issue 5, pp 497–505

Nifedipine limits infarct size via NO-dependent mechanisms in dogs

Authors

  • Hiroshi Asanuma
    • Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka Pref. 565-0871, Japan, E-mail: kitakaze@medone.med.osaka-u.ac.jp
  • Masafumi Kitakaze
    • Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka Pref. 565-0871, Japan, E-mail: kitakaze@medone.med.osaka-u.ac.jp
  • Hiroharu Funaya
    • Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka Pref. 565-0871, Japan, E-mail: kitakaze@medone.med.osaka-u.ac.jp
  • Seiji Takashima
    • Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka Pref. 565-0871, Japan, E-mail: kitakaze@medone.med.osaka-u.ac.jp
  • Tetsuo Minamino
    • Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka Pref. 565-0871, Japan, E-mail: kitakaze@medone.med.osaka-u.ac.jp
  • Koichi Node
    • Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka Pref. 565-0871, Japan, E-mail: kitakaze@medone.med.osaka-u.ac.jp
  • Yasuhiko Sakata
    • Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka Pref. 565-0871, Japan, E-mail: kitakaze@medone.med.osaka-u.ac.jp
  • Masanori Asakura
    • Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka Pref. 565-0871, Japan, E-mail: kitakaze@medone.med.osaka-u.ac.jp
  • Shoji Sanada
    • Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka Pref. 565-0871, Japan, E-mail: kitakaze@medone.med.osaka-u.ac.jp
  • Yoshiro Shinozaki
    • Tokai University School of Medicine, Department of Physiology, Isehara, Japan
  • Hidezo Mori
    • Tokai University School of Medicine, Department of Physiology, Isehara, Japan
  • Tsunehiko Kuzuya
    • Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka Pref. 565-0871, Japan, E-mail: kitakaze@medone.med.osaka-u.ac.jp
  • Michihiko Tada
    • Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka Pref. 565-0871, Japan, E-mail: kitakaze@medone.med.osaka-u.ac.jp
  • Masatsugu Hori
    • Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka Pref. 565-0871, Japan, E-mail: kitakaze@medone.med.osaka-u.ac.jp
Original contribution

DOI: 10.1007/s003950170032

Cite this article as:
Asanuma, H., Kitakaze, M., Funaya, H. et al. Basic Res Cardiol (2001) 96: 497. doi:10.1007/s003950170032

Abstract

Objectives Amlodipine increases NO levels in coronary vessels and aorta via bradykinin-dependent mechanisms in vitro. We have previously reported that nifedipine increases cardiac NO levels in the ischemic canine hearts, suggesting that nifedipine may also have protective effects against ischemia and reperfusion injury, because the enhancement of NO production limits infarct size. We tested whether nifedipine limits infarct size via NO-dependent mechanisms. Methods In open chest dogs, the left anterior descending coronary artery was perfused with blood through a bypass tube and occluded for 90 min followed by 6 hours of reperfusion. Infarct size was assessed at 6 hours of reperfusion. Nifedipine of 3 or 6 μg/kg/min was infused into the bypass tube between 10 min prior to the onset of ischemia and 60 min of reperfusion. Results Neither systemic blood pressure nor heart rate changed during infusion of nifedipine. Infarct size was reduced by the administration of nifedipine (3 or 6 μg/kg/min) compared with the untreated condition (25.6 plusmn; 2.6 and 19.1 ± 3.5 vs. 43.4 ± 5.6 %, respectively), which was completely blunted by L-NAME (45.0 ± 3.6 and 45.4 ± 4.2 vs. 47.9 ± 3.9 % in the nifedipine (3 or 6 μg/kg/min) with L-NAME groups vs. the L-NAME group). Myeloperoxidase activity of the myocardium increased after 6 hours of reperfusion, which was attenuated by nifedipine. The limitation of infarct size and the attenuation in myeloperoxidase activity were completely blunted by L-NAME. There were no significant differences in collateral blood flow at 45 min of ischemia between each group. Conclusions We conclude that the Ca channel blocker, nifedipine, limits infarct size via NO-dependent mechanisms.

Key words Ca channel – endothelium – ischemia – NO – reperfusion

Copyright information

© Steinkopff Verlag 2001