Effects of Ca antagonists on the norepinephrine release and contractile responses of isolated canine saphenous veins to transmural nerve stimulation

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 X 10(-5) M, while this drug at 3 X 10(-6)-3 X 10(-5) M concentration-dependently inhibited the TNS-evoked contraction. Verapamil, 3 X 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.