Vasorelaxant effect of mexiletine in mesenteric resistance arteries of rats

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Abstract
1 The vascular action of mexiletine, a class Ib antiarrhythmic agent, was investigated in the mesenteric resistance arteries of rats. 2 The second order branch of the mesenteric artery was cut into rings and changes in isometric tension were recorded. 3 Mexiletine (10−6–10−3 m) evoked concentration-dependent, endothelium-independent relaxations in arteries contracted with noradrenaline. 4 Mexiletine (10−4 m) did not affect the contraction induced by noradrenaline in Ca2+-free solution, while the compound inhibited the contraction induced by CaCl2 in noradrenaline-activated arteries. 5 The relaxation induced by mexiletine was less pronounced in arteries contracted with high KCl than in those contracted with noradrenaline. 6 Mexiletine induced identical relaxations in arteries contracted with noradrenaline in high KCl solution containing verapamil and in Krebs solution. 7 Thus, mexiletine induces relaxations by inhibiting transmembrane Ca2+ movement, but not Ca2+ release from the intracellular store site in mesenteric resistance arteries of rats. It is speculated that mexiletine possesses greater inhibitory effects against noradrenaline-activated, verapamil-insensitive (receptor-operated) Ca2+ channels than against verapamil-sensitive (voltage-dependent) channels.