Author + information
- Received September 5, 1995
- Revision received May 21, 1996
- Accepted August 9, 1996
- Published online November 15, 1996.
- Takayuki Miki, MD,
- Tetsuji Miura, MD, PhD∗,
- Nobuyuki Ura, MD, PhD,
- Takashi Ogawa, MD,
- Katsuo Suzuki, MD,
- Kazuaki Shimamoto, MD, PhD and
- Osamu Iimura, MD, PhD
- ↵∗Address for correspondence:: Dr. Tetsuji Miura, Second Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, Sapporo, 060, Japan.
Objectives. To investigate the role of kinin in preconditioning against infarction, the present study assessed the effect of captopril, a kininase II inhibitor, on preconditioning and arterial plasma kinin levels.
Background. Recent studies suggest a possible contribution of kinin to preconditioning against infarction. However, its role and the site of kinin production remain uncharacterized.
Methods. Six groups of rabbits (n = 6 to 13) underwent 30-min coronary occlusion and 3-h reperfusion. The infarct size and area at risk were determined by tetrazolium staining and fluorescent particles, respectively. Arterial blood was sampled under baseline conditions, before the 30-min ischemia and after reperfusion for radioimmunoassay of the kinin level.
Results. Infarct size expressed as a percentage of area at risk (%IS/AR) was 42.9 ± 2.9% (mean ± SEM) in the control group, 34.5 ± 3.3% in the group preconditioned with 2 min of ischemia/5 min of reperfusion and 41.7 ± 5.1% in the group given captoril (1 mg/kg body weight) alone before the 30-min ischemia. These %IS/AR values were not significantly differenct between the three groups. However, a combination of captopril and subsequent preconditioning with 2 min of ischemia markedly limited %IS/AR to 21.2 ± 2.4%. This potentiation of 2 min of preconditioning by captopril was not observed when 2 μg/kg body weight of Hoe 140, a specific bradykinin B2 receptor antagonist, was administered before preconditioning (%IS/AR = 41.2 ± 5.7%), whereas How 140 alone did not modify infarct size (%IS/AR = 38.5 ± 5.1%). Arterial plasma kinin levels were comparable between the control rabbits, the group given captopril alone and the group that received captopril plus 2 min of preconditioning at baseline (3.8 ± 1.0, 6.3 ± 1.9 and 5.2 ± 1.7 pg/ml, respectively), and there was no significant change in kinin levels after the captopril injection or the combination of captopril plus 2 min of preconditioning.
Conclusions. The present results indicate that captopril is capable of potentiating preconditioning without increasing the arterial kinin level and that the beneficial effect of captopril can be inhibited by Hoe 140. These findings support the hypothesis that kinin produced locally in the heart during preconditioning may contribute to the cardioprotective mechanism through bradykinin receptor activation.
☆ This study was supported in part by Grant-in-Aid for Scientific Research 04670547 (Dr. Miura) from the Ministry of Education, Science and Culture, Tokyo, Japan. Hoe 140 was provided by Bernwald A. Scholkens, MD, Hoechst AG, Frankfurt, Germany.
- Received September 5, 1995.
- Revision received May 21, 1996.
- Accepted August 9, 1996.