Positive inotropic and chronotropic effects and coronary vasodilation in vitro by two antiasthmatic xanthines with different abilities to antagonize adenosine.

Abstract

The direct actions and the ability to antagonize adenosine of theophylline (1,3-dimethylxanthine) and enprofylline (3-propylxanthine) were examined in isolated guinea pig heart preparations. Enprofylline was approximately six times as potent as theophylline in reducing coronary perfusion pressure, and between three and five times more potent in increasing rate and force of contraction in isolated perfused hearts, spontaneously beating right atrias, and electrically stimulated left atrias. Adenosine reduced the coronary perfusion pressure and had negative inotropic and chronotropic actions. Theophylline (5-75 microM) concentration-dependently antagonized the coronary vasodilation and the negative chronotropic and inotropic actions of adenosine, whereas enprofylline (2.5-75 microM) did not antagonize adenosine. Since adenosine may be a protective autacoid in the heart under select stress conditions, the possibility that adenosine nonblocking xanthines, like enprofylline, may offer therapeutic advantages over theophylline should be investigated.