Adenosine A2a-receptor activation increases contractility in isolated perfused hearts

Adenosine A2a-receptor activation enhances shortening of isolated cardiomyocytes. In the present study the effect of A2a-receptor activation on the contractile performance of isolated rat hearts was investigated by recording left ventricular pressure (LVP) and the maximal rate of LVP development (+dP/d tmax). With constant-pressure perfusion, adenosine caused concentration-dependent increases in LVP and +dP/d tmax, with detectable increases of 4.1 and 4.8% at 10−6M and maximal increases of 12.0 and 11.1% at 10−4M, respectively. The contractile responses were prevented by the A2a-receptor antagonists chlorostyryl-caffeine and aminofuryltriazolotriazinyl-aminoethylphenol (ZM-241385) but were not affected by the β1-adrenergic antagonist atenolol. The adenosine A1-receptor antagonist dipropylcyclopentylxanthine and pertussis toxin potentiated the positive inotropic effects of adenosine. The A2a-receptor agonists ethylcarboxamidoadenosine and dimethoxyphenyl-methylphenylethyl-adenosine also enhanced contractility. With constant-flow perfusion, 10−5M adenosine increased LVP and +dP/d tmaxby 5.5 and 6.0%, respectively. In the presence of the coronary vasodilator hydralazine, adenosine increased LVP and +dP/d tmaxby 7.5 and 7.4%, respectively. Dipropylcyclopentylxanthine potentiated the adenosine contractile responses with constant-flow perfusion in the absence and presence of hydralazine. These increases in contractile performance were also antagonized by chlorostyryl-caffeine and ZM-241385. The results indicate that adenosine increases contractile performance via activation of A2areceptors in the intact heart independent of β1-adrenergic receptor activation or changes in coronary flow.