title: 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.
mesh_terms: D000320:Adrenergic Fibers / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009411:Nerve Endings / Q000502:physiology; D009529:Nicardipine; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D012501:Saphenous Vein / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D014316:Tritium; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D014316:Tritium; D014700:Verapamil; D009529:Nicardipine; D004110:Diltiazem; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine