Effect of acetylcholine on changes in contractility, heart rate and phosphorylase activity produced by isoprenaline, salbutamol and amino-phylline in the perfused guinea-pig heart.

1. Isolated perfused hearts of guinea-pigs were given graded doses of isoprenaline, salbutamol and aminophylline, both before and during acetylcholine infusion. 2. The three agonists produced increases in contractile force, heart rate and ventricular glycogen phosphorylase activity. 3. Acetylcholine, in the concentration used, had no effect on any of the measured variables but did antagonize the effects of the three agonists on contractility and phosphorylase activity. The positive chronotropic responses were unaltered by acetylcholine infusion. 4. The ratio of the dose required for a standard heart rate response to the dose producing a standard contractile force response was different for each agonist. 5. The selective antagonism of the contractile response to isoprenaline, salbutamol and aminophylline suggest that different mechanisms are involved in the initiation of positive inotropic and chronotropic responses.