Evidence for the possible involvement of Ca2+ entry blockade in the relaxation by class I antiarrhythmic drugs in the isolated pig coronary smooth muscle.

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.