Basic Research in Cardiology

, Volume 96, Issue 5, pp 497–505

Nifedipine limits infarct size via NO-dependent mechanisms in dogs

  • Hiroshi Asanuma
  • Masafumi Kitakaze
  • Hiroharu Funaya
  • Seiji Takashima
  • Tetsuo Minamino
  • Koichi Node
  • Yasuhiko Sakata
  • Masanori Asakura
  • Shoji Sanada
  • Yoshiro Shinozaki
  • Hidezo Mori
  • Tsunehiko Kuzuya
  • Michihiko Tada
  • Masatsugu Hori
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

Authors and Affiliations

  • Hiroshi Asanuma
    • 1
  • Masafumi Kitakaze
    • 1
  • Hiroharu Funaya
    • 1
  • Seiji Takashima
    • 1
  • Tetsuo Minamino
    • 1
  • Koichi Node
    • 1
  • Yasuhiko Sakata
    • 1
  • Masanori Asakura
    • 1
  • Shoji Sanada
    • 1
  • Yoshiro Shinozaki
    • 2
  • Hidezo Mori
    • 2
  • Tsunehiko Kuzuya
    • 1
  • Michihiko Tada
    • 1
  • Masatsugu Hori
    • 1
  1. 1.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.jpJP
  2. 2.Tokai University School of Medicine, Department of Physiology, Isehara, JapanJP