Effects of Verapamil on [3H]Norepinephrine Release

Abstract

Summary: 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 (10-6-10-4M) 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 α2-adrenoceptors. The greatest increase in 3H-overflow— around 400% in the various groups—was observed after perfusion with 10-4M verapamil. In other experiments, we found that verapamil also enhanced 3H-overflow from vessels not stimulated transmurally; this effect again was dose-related (p < 0.001). In the vas deferens of the guinea pig, 10−5M verapamil increased spontaneous and electrical stimulation-induced 3H-release (p < 0.001), whereas superfusion of the tissue with 10-9 and 10-7M verapamil was ineffective. The results indicate that verapamil can act on sympathetic nerves to release norepinephrine.