The effect of nifedipine on norepinephrine release

Recently, we reported that verapamil and diltiazem caused a marked release of 3H from 3H-norepinephrine labelled tissues with rich sympathetic innervation. In the present study, we investigated the effect of nifedipine in rat tail artery and guinea-pig vas deferens. In vitro superfusion of the arteries with nifedipine (10(-6) - 10(-4) M) caused a significant release of 3H both in spontaneously hypertensive and in normotensive rats, particularly after the highest concentration of the drug. Release of 3H induced by transmural stimulation (1 Hz, 2msec, 10 V) was also significantly greater in vessels superfused with nifedipine than in controls. Column chromatographic analysis revealed that nifedipine did not alter the proportion of norepinephrine and its metabolites in spontaneous or electrical stimulation induced 3H-overflow suggesting that it releases norepinephrine from sympathetic nerves intracellularly. Nifedipine (10(-9) - 10(-4) M) superfusion caused release of 3H-norepinephrine also in the vas deferens of guinea-pig. The effect of nifedipine observed in the present study was similar but less pronounced than that described by us for verapamil and diltiazem. The results indicate that calcium entry blockers act on sympathetic nerves and that this effect is likely explained by an action other than inhibition of Ca2+ influx into the cells.