Inhibitory effect of lidoflazine on contractions of isolated canine coronary arteries caused by norepinephrine, 5-hydroxytryptamine, high potassium, anoxia and ergonovine maleate

Abstract

Experiments were performed on isolated coronary arteries to determine whether or not lidoflazine, an agent reported to be beneficial in the treatment of angina pectoris, is effective in antagonizing coronary vasoconstriction. Segments of canine circumflex and right coronary arteries were suspended in organ chambers filled with aerated Krebs-Henseleit solution (37°C) for continuous isometric tension recordings. Dose-dependent contractions were obtained with norepinephrine (in presence of propranolol) and 5-hydroxytryptamine; these contractile responses were antagonized by phentolamine and methysergide, respectively. Lidoflazine caused long-lasting, and dose-dependent inhibition of the responses to both norepinephrine and 5-hydroxytryptamine. High K+ solution (30 mM) caused sustained contraction of the coronary segments; these responses were depressed in a dose-dependent manner by lidoflazine. Lidoflazine slightly augmented relaxations caused by adenosine. Addition of Ca++ to the bath solution partially reversed the inhibitory effect of lidoflazine, which indicates that the compounds acts by inhibiting the influx of extracellular Ca++. Segments incubated in solution containing 20 mM K+ and subjected to anoxia exhibited transient contractions which were inhibited by lidoflazine. Ergonovine maleate caused contractures of the coronary arteries which also were antagonized in a dose-dependent manner by lidoflazine. These experiments demonstrate the ability of lidoflazine to counteract contractions of coronary vascular smooth muscle caused by factors which may be involved in the etiology of coronary vasospasm.