title: Evidence for the possible involvement of Ca2+ entry blockade in the relaxation by class I antiarrhythmic drugs in the isolated pig coronary smooth muscle.
abstract: Effects of several Na+ channel blockers (i.e., class I antiarrhythmic agents), procainamide, quinidine, lidocaine, mexiletine, propafenone, were investigated in the isolated endothelium-denuded pig coronary artery focusing on the possible involvement of the blockade of Ca2+ channels and/or opening of K+ channels in the relaxant responses. All drugs except procainamide induced a concentration-dependent full relaxation of the coronary artery precontracted with high-KCl (30 mM, 80 mM). Inhibitions by procainamide of both high-KCl-induced contractions were less than 50% even at a concentration of 3 x 10(-2) M. Both high-KCl contractions were diminished by an L-type Ca2+ channel blocker, diltiazem, in a concentration-dependent manner. In contrast, cromakalim failed to inhibit 80 mM KCl-induced contraction. Tetrodotoxin (3 x 10(-5) M) did not affect the relaxant actions of the tested class I antiarrhythmic agents in high-KCl (80 mM)- or prostaglandin F2alpha-contracted muscle. The inhibitions by these class I antiarrhythmic agents of high-KCl-induced contraction were significantly attenuated when extracellular CaCl2 was increased from 2 mM to 20 mM. Furthermore, procainamide, quinidine, lidocaine, mexiletine as well as diltiazem decreased both cytoplasmic Ca2+ level ([Ca2+](cyt)) and muscle tension elevated by high-KCl in fura-2-loaded coronary preparations. These findings suggest that blockade of voltage-gated Ca2+ channels is involved in the relaxing action of these class I antiarrhythmic drugs in pig coronary artery. Blockade of Na+ channel and/or opening of K+ channels does not seem to play the principal role in the mechanism by which these antiarrhythmic drugs relax coronary artery.
authors.affiliation: Department of Pharmacology, Toho University School of Pharmaceutical Sciences, 2-2-1 Miyama, Funabashi-City, Chiba 274-8510, Japan. yotanaka@phar.toho-u.ac.jp
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Makoto
authors.initials: M
authors.lastname: Kamibayashi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Imai
authors.forename: Hikaru
authors.initials: H
authors.lastname: Tanaka
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakahara
authors.forename: Kunio
authors.initials: K
authors.lastname: Ishii
authors.forename: Koki
authors.initials: K
authors.lastname: Shigenobu
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000145:classification / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002122:Calcium Chloride / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D019806:Cromakalim / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D013552:Swine; D013779:Tetrodotoxin / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D014665:Vasodilator Agents; D019806:Cromakalim; D013779:Tetrodotoxin; D011189:Potassium Chloride; D004110:Diltiazem; D002122:Calcium Chloride