Cyclooxygenase-2 does not mediate late preconditioning induced by activation of adenosine A1 or A3 receptors

Eitaro Kodani, Ken Shinmura, Yu Ting Xuan, Hitoshi Takano, John A. Auchampach, Xian Liang Tang, Roberto Bolli

研究成果: Article査読

32 被引用数 (Scopus)

抄録

Recent studies have demonstrated that the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA) and the adenosine A3 receptor agonist N6-(3-iodobenzyl)adenosine-5′-N-methyluronamide (IB-MECA) produce a delayed phase of protection against infarction similar to the late phase of ischemic preconditioning (PC). However, the mechanism for adenosine A1 or A3 receptor-induced late PC remains unknown. The goal of this study was to determine whether the delayed cardioprotective effects of adenosine A1 or A3 receptors are mediated by cyclooxygenase-2 (COX-2), which is an obligatory mediator of ischemic PC. We found that COX-2 protein expression (Western blotting) did not increase 24 h after the administration of either CCPA (100 μg/kg iv) or IB-MECA (300 μg/kg iv) compared with controls. To probe the role of constitutive COX-2 expression, conscious rabbits were subjected to 30-min coronary occlusion followed by 72-h reperfusion. Twenty-four hours before the occlusion, the rabbits were pretreated with CCPA (100 μg/kg iv) or IB-MECA (300 μg/kg iv). Both CCPA and IB-MECA resulted in a marked (∼47%) reduction in infarct size vs. controls [36.2 ± 4.0% of the risk region (n = 9), 31.2 ± 4.7% (n = 9), and 59.5 ± 3.8% (n = 9), respectively; P < 0.05], similar to that induced by the late phase of ischemic PC [31.8 ± 3.2% (n = 9)]. The selective COX-2 inhibitor N-(2-[cyclohexyloxy]4-nitrophenyl)methanesulfonamide (NS-398, 5 mg/kg), which abolished the protective effect of ischemic late PC, failed to block the protection of either CCPA or IB-MECA, indicating that COX-2 does not mediate the delayed protection of either CCPA or IB-MECA [CCPA + NS-398, 29.1 ± 3.4% (n = 7); IB-MECA + NS-398, 34.9 ± 2.9% (n = 8)]. NS-398 in itself did not affect infarct size [54.9 ± 3.7% (n = 9)]. Taken together, these results demonstrate that, in contrast to ischemia-induced late PC, the mechanisms of adenosine A1 or A3 receptor-induced late PC is independent of COX-2.

本文言語English
ページ(範囲)H959-H968
ジャーナルAmerican Journal of Physiology - Heart and Circulatory Physiology
281
2 50-2
DOI
出版ステータスPublished - 2001

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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