Tetrodotoxin-resistant relaxation to transmural nerve stimulation in isolated saphenous vein

The response to transmural nerve stimulation (TNS) was characterized in rings of canine saphenous veins following sympathetic (guanethidine 10(-4) mol/l; phenoxybenzamine 2 X 10(-5) mol/l; propranolol 2 X 10(-6) mol/l) and muscarinic blockade (atropine 5 X 10(-6) mol/l). In preparations which were contracted with prostaglandin F2 alpha, TNS was applied as intermittent trains of stimuli of 30 s duration at frequencies of 1-32 Hz. This stimulus elicited a frequency-dependent relaxation [maximum relaxation 3.4 +/- 0.21 (SE) g]. This relaxation was present in rings denuded of endothelium and was not altered significantly by cimetidine (10(-4) mol/l), indomethacin (10(-5) mol/l), aminophylline (10(-5) mol/l), or cyproheptadine (10(-6) mol/l). It was abolished by the Na+-K+-ATPase inhibitor ouabain (2 X 10(-4) mol/l) and in zero-K+ Krebs solution. When the experiment was repeated following storage of the isolated saphenous veins for 9 days at 4 degrees C TNS failed to induce any relaxation. However, the relaxation in fresh rings was not abolished by tetrodotoxin (10(-6) mol/l). The present study demonstrates a nonadrenergic noncholinergic relaxation to TNS in the saphenous vein which could be mediated by 1) a tetrodotoxin-resistant nerve or 2) a direct effect of TNS on the smooth muscle.