Abstract

Changes in ventricular contractility in respouse to a wide range of doses of acetylcholine from 0.01 to 300 µg were investigated in the blood-perfused canine papillary muscle preparation. A negative inotnopic response occurred immediately after administration of 0.01 to 10 µg of acetyicholine and was followed by a positive response 1 to 2.5 minutes later. Large doses of acetylcholine, 10 to 300 µg, caused a quickly induced positive inotropic response within the time period occupied by the negative phase mentioned above. Negative and positive inotropic responses competed with each other, but with larger doses the negative inotropic response was completely replaced by the positive one. Atropine blocked not only the negative inotropic response but also the slowly induced positive one, whereas it markedly en hanced the rapid positive inotropic response induced by large doses of acetylcholine. The rapid positive inotropic response to large doses of acetyicholine was blocked by beta adrenergic blocking agents (alprenolol or propranolol), ganglionic blocking agents (tetraethylammonium or hexamethonium) and tetrodotoxin. The negative and the slowly induced positive inotropic effects of acetyicholine were not affected by these drugs. These observations demonstrate that acetyicholine has positive inotropic effects on the canine papillary muscle that are both muscarinicand nicotinic.