Vasorelaxant effect of mexiletine in mesenteric resistance arteries of rats.
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 Ca(2+)-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.
Second Department of Internal Medicine, Nagoya City University Hospital, Japan.
Y
Y
Dohi
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Kojima
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Sato
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology*; D008801:Mexiletine / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D012964:Sodium / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects*
D008801:Mexiletine; D002110:Caffeine; D011189:Potassium Chloride; D012964:Sodium; D009638:Norepinephrine