Anti-muscarinic effect of alinidine on acetylcholine-induced vasodilation in isolated and perfused dog coronary arteries.

The effect of alinidine, a bradycardic agent, on the vasodilator responses to acetylcholine was examined in isolated and perfused dog coronary arteries. Single injections of acetylcholine (10(-12)-10(-6) mol) and carbachol (10(-10)-10(-6) mol) produced dose-dependent vasodilations. The endothelial removal by a bolus injection of saponin (1 mg) inhibited those vasodilations. Alinidine (10(-6) M) shifted the dose-response curves of acetylcholine and carbachol to the right, but it did not affect those for isosorbide dinitrate, isoproterenol and adenosine. The rank order of potency of muscarinic antagonists for inhibiting the acetylcholine-induced vasodilation was 4-DAMP greater than or equal to atropine greater than AF-DX 116 greater than or equal to pirenzepine greater than alinidine. Alinidine was approximately 100 times less potent than atropine. Single injection of alinidine (10(-8)-10(-6) mol) dilated the dog coronary artery in a dose-related manner. The vasodilation was not affected by the pretreatment with phentolamine (10(-6) M), pindolol (10(-6) M), atropine (10(-6) M), chlorpheniramine (10(-6) M), cimetidine (10(-6) M) or methysergide (10(-6) M). These results suggest that alinidine has a weak anti-muscarinic effect on the endothelium-dependent vasodilation of the dog coronary artery.