Relationship between tissue content of TC-81 and relaxation of rat aorta

Abstract This study dealt with the relationship between the relaxant action of TC-81, a new Ca 2+ antagonist, and its distribution in rat aorta depolarized by high K + (65.4 mM). The inhibitory effect by TC-81 on K + -induced contraction and 45 Ca 2+ uptake was strongly time-dependent. TC-81 and nicardipine, each 10 −9 M, produced gradual relaxation of high-K + -induced contraction. The tissue contents of TC-81 and nicardipine increased with time courses that reflected decreasing tension. Both the maximum tissue content of TC-81 and the maximum relaxation were significantly greater than those for nicardipine. Also, the relaxations produced by TC-81 and nicardipine were correlated with the logarithm of the content of each drug in muscle tissues. However, the dissociation of TC-81 from the tissues was slower than that of nicardipine. The data suggest that the action of TC-81 is closely related to a gradual distribution of drug into muscle tissue, resulting in a slow onset of action. Also, the saturation time of TC-81 was longer than that of nicardipine, thereby accounting for the greater relaxation with TC-81.