Effects of verapamil on [3H]norepinephrine release.

If calcium entry blocking drugs affect norepinephrine release, this may alter their cardiovascular action by modifying the activity of baroreceptor reflexes. We investigated the effect of verapamil on 3H-release in [3H]norepinephrine-incubated rat arteries and guinea pig vas deferens. Superfusion of tail artery with verapamil (10(-6) - 10(-4) M) increased the 3H-overflow induced by transmural stimulation (1 Hz, 2 ms, 10 V) both in Wistar Kyoto and in spontaneously hypertensive rats. The effect was present also in vessels pretreated with cocaine to inhibit neuronal uptake or with yohimbine to block alpha 2-adrenoceptors. The greatest increase in 3H-overflow--around 400% in the various groups--was observed after perfusion with 10(-4) M verapamil. In other experiments, we found that verapamil also enhanced 3H-overflow from vessels not stimulated transmurally; this effect again was dose-related (p less than 0.001). In the vas deferens of the guinea pig, 10(-5) M verapamil increased spontaneous and electrical stimulation-induced 3H-release (p less than 0.001), whereas superfusion of the tissue with 10(-9) and 10(-7) M verapamil was ineffective. The results indicate that verapamil can act on sympathetic nerves to release norepinephrine.