Responses of isolated and perfused dog coronary arteries to acetylcholine, norepinephrine, KCl, and diltiazem before and after removal of the endothelial cells by saponin.

The vascular responses to acetylcholine (ACh), norepinephrine (NE), KCl, and diltiazem were examined before and after removal of endothelial cells by an intraluminal bolus injection of saponin (1 mg) in isolated and perfused dog coronary arteries. Without any precontraction, ACh induced a long-lasting vasodilation in small doses (less than 1 microgram), and an initial brief vasoconstriction was occasionally accompanied in large doses. These vascular responses to ACh were not significantly affected by the pretreatment with propranolol (5 X 10(-6) mol/l). The endothelial removal by intraluminal saponin was confirmed electron microscopically. After 20-60 min of saponin treatment, the responses to drugs were observed and compared with the control. The ACh-induced vasodilation was significantly attenuated by saponin (P less than 0.01), but the ACh-induced vasoconstriction was not affected by it. The vasodilation was blocked by atropine. The NE- and KCl-induced vasoconstrictions and diltiazem-induced vasodilation were not affected by saponin treatment. It is suggested that: (1) ACh produced a vasodilation in the nonpreconstricted condition of dog coronary arteries; (2) the vasodilation caused by ACh is mostly endothelium-dependent, which is considered to be mediated by muscarinic receptors; and (3) the vascular responses to NE, KCl, and diltiazem and the vasoconstriction produced by ACh are not influenced by removal of the endothelium in a relatively large epicardial coronary artery of the dog.