Selective attenuation of isoproterenol-stimulated arrhythmic activity by a partial agonist of adenosine A1 receptor.

Abstract

The goal of this study was to examine the hypothesis that a partial agonist of the adenosine A1 receptor (A1AdoR) may cause a greater attenuation of catecholamine-induced ventricular arrhythmic activity than of contractility. The effects of CVT-2759 and adenosine, a partial and a full agonist of the A1AdoR, on isoproterenol-stimulated arrhythmic activity and contractility of guinea pig isolated ventricular myocytes were determined. CVT-2759 (10 micromol/L) and adenosine (10 micromol/L) significantly inhibited isoproterenol-induced arrhythmic activity (aftercontraction and transient inward current) but did not reduce the amplitudes of twitch shortening and L-type Ca2+ current. Increasing the concentration of the full agonist adenosine from 10 to 100 micromol/L, however, caused significant attenuation of twitch shortening as well as aftercontractions, whereas increasing the concentration of the partial agonist CVT-2759 from 10 to 100 micromol/L did not. CVT-2759 also significantly inhibited isoproterenol-induced spontaneous ventricular beats in isolated hearts. In contrast to adenosine, CVT-2759 neither activated adenosine-sensitive K+ current nor shortened the duration of the atrial APD. The present results support the hypothesis and suggest a potential role for a partial agonist of the A1AdoR in the treatment of cardiac arrhythmias.