Abstract
Effects of verapamil, diltiazem and nicardipine on tritium overflow and contraction evoked by transmural nerve stimulation (TNS) were evaluated using canine saphenous vein strips preincubated with [3H]norepinephrine. External Ca2+ was required for both tritium overflow and contraction evoked by TNS. All the Ca antagonists tested significantly increased the spontaneous overflow of tritium in a concentration-dependent manner with no changes in basal tension. Verapamil in concentrations lower than 10-5 M significantly enhanced the TNS-evoked tritium overflow, but reduced it at 3×10-5 M, while this drug at 3×10-6-3×10-5 M concentration-dependently inhibited the TNS-evoked contraction. Verapamil, 3×10-5 M, inhibited the TNS-evoked contraction more strongly than the evoked tritium overflow. On the other hand, diltiazem and nicardipine in concentrations higher than 10-5 M significantly inhibited both tritium overflow and contraction evoked by TNS. There was no significant difference between inhibitions of the TNS-evoked tritium overflow and contraction by either diltiazem or nicardipine. Neither increase in the spontaneous tritium overflow nor inhibitions of the TNS-evoked tritium overflow and contraction by nicardipine appeared to be related to its phosphodiesterase inhibiting activity. These results suggest that diltiazem and nicardipine may inhibit the TNS-evoked contraction mainly by inhibiting Ca2+-dependent transmitter release from the adrenergic nerve endings, whereas verapamil may inhibit it by restricting the availability of Ca2+ at the postsynaptic sites and in the highest concentration used, by additional inhibition of transmitter release.
