Cholinergic mechanisms on the heart and coronary circulation.

1. The effects of rapid intracoronary injection of acetylcholine (ACh) were studied in anaesthetized open chest dogs. Changes in phasic coronary blood flow were followed with non-cannulating electromagnetic flow probes and in contractile force with isometric strain gauges.2. Increasing doses of ACh from 0.01 to 100 mug produced progressively larger increases in systolic and diastolic coronary blood flow and progressive decreases in end-diastolic vascular resistance which were blocked by atropine but not by propranolol.3. Contractile force showed both negative and positive responses. The negative inotropic effect was small and was blocked by atropine but not by propranolol. The threshold for the negative inotropic response was higher than for the coronary vasodilator effect and the dose response curve was flatter. The positive inotropic response usually showed two components. One component reached its maximum 13 to 18 s after injection, had a high threshold (over 1 mug), was potentiated by atropine and blocked by propranolol. The other reached its maximum 25 to 60 s after the injection, had a threshold between 0.01 and 0.1 mug, and was blocked by atropine but not by propranolol.4. These results suggest that the coronary dilator response, the negative inotropic response and part of the positive inotropic response are mediated through "muscarinic" receptors. The remaining component of the positive inotropic response appears to involve catecholamine release.