Hypoxic preconditioning in isolated rat hearts: Non-involvement of activation of adenosine A(1) receptor, Gi protein, and ATP-sensitive K+ channel

Author(s): Nasa, Y., Takeo, S.

Journal/Book: Heart Vessels. 1995; 10: 175 Fifth Ave, New York, NY 10010. Springer Verlag. 294-303.

Abstract: Activation of the adenosine A(1)(A(1)) 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 A(1) 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 postischemic contractile dysfunction. neither the activation of the A(1) 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.

Note: Article S Takeo, Univ Tokyo, Dept Pharmacol, Hachioji, Tokyo 19203, Japan

Keyword(s): preconditioning; hypoxia; adenosine A(1) receptor; KATP-channel; Gi-protein; MYOCARDIAL INFARCT SIZE; ISCHEMIC CONTRACTURE; POSTISCHEMIC DYSFUNCTION; PROTECTIVE MECHANISM; K(ATP) CHANNELS; GLIBENCLAMIDE; DOGS; RECOVERY; REPERFUSION; ARRHYTHMIAS

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