Effect of N6-Cyclopentyladenosine on Ouabain-Induced Toxicity in Isolated Guinea Pig Atria

ABSTRACT The effect of N6-cyclopentyladenosine (CPA), an A1-selective adenosine agonist, was studied on ouabain-induced toxicity in spontaneously beating isolated guinea pig atria. CPA (2-16 nM) produced a dose-dependent decrease in the force of contractions (34%-51%) and in the rate of contractions (22%-48%). CPA significantly increased the time of onset of arrhythmia (toxicity) induced by ouabain (1.2 μM) when it was administered 10 min before ouabain was added in organ bath. Ouabain (1.2 μM) alone produced arrhythmia at 7 min and either asystole or standstill at 22 min. CPA (8 nM) increased the time required to produce arrhythmia to 27.5 min and prolonged beating atria to more than 63 min and prevented the occurrence of asystole. These findings indicated that CPA produces direct cardiac action, probably due the inhibition of cardiac Na+ and Ca2+ channels. Moreover, our results suggest that CPA may reduce the membrane conduction through inhibition of ionic channels, which decrease ouabain-induced toxicity.