Yabe K, Nasa Y, Takeo S
Department of Pharmacology, Tokyo University of Pharmacy and Life Science, Japan.
Heart Vessels. 1995;10(6):294-303. doi: 10.1007/BF02911387.
Activation of the adenosine A1(A1) receptor, Gi protein, and ATP-sensitive K+ (KATP)-channel system has been shown to play an important role in the cardioprotective effects of ischemic preconditioning in dogs. The present study was undertaken to elucidate the possible involvement of this system in hypoxic preconditioning, which ameliorates injury induced by prolonged ischemia and subsequent reperfusion in perfused rat hearts. Ten minutes of hypoxic preconditioning resulted in an appreciable improvement of post-ischemic cardiac contractile recovery. This was associated with a significant reduction in the release of creatine kinase (CK) from reperfused hearts. Hypoxic preconditioning shortened the time to ischemic contracture onset and prevented a further rise in left ventricular end-diastolic pressure (LVEDP) during reperfusion. Neither the selective A1 receptor antagonist, 8-cyclopentyltheophylline (CPT) nor the KATP channel blocker, glibenclamide, altered the beneficial effects of hypoxic preconditioning. In vivo pretreatment with an inhibitor of Gi protein, pertussis toxin (PTX), also did not diminish the preconditioning effect. The results suggest that, although hypoxic preperfusion ameliorates post-ischemic contractile dysfunction, neither the activation of the A1 receptor, nor the opening of the KATP-channel, nor transduction through Gi protein are involved in the post-ischemic functional recovery of hypoxic preconditioning in the perfused rat heart.
腺苷A1（A1）受体、Gi蛋白和ATP敏感性钾离子（KATP）通道系统的激活已被证明在犬缺血预处理的心脏保护作用中发挥重要作用。本研究旨在阐明该系统在低氧预处理中可能的参与情况，低氧预处理可改善灌注大鼠心脏长时间缺血及随后再灌注所诱导的损伤。十分钟的低氧预处理导致缺血后心脏收缩功能恢复有明显改善。这与再灌注心脏中肌酸激酶（CK）释放的显著减少相关。低氧预处理缩短了缺血性挛缩开始的时间，并防止了再灌注期间左心室舒张末期压力（LVEDP）的进一步升高。选择性A1受体拮抗剂8-环戊基茶碱（CPT）和KATP通道阻滞剂格列本脲均未改变低氧预处理的有益作用。用Gi蛋白抑制剂百日咳毒素（PTX）进行体内预处理也未减弱预处理效果。结果表明，尽管低氧预灌注可改善缺血后收缩功能障碍，但A1受体的激活、KATP通道的开放以及通过Gi蛋白的转导均不参与灌注大鼠心脏低氧预处理的缺血后功能恢复。
