SUMMARY Adenosine and the adenine nucleotides caused a greater relaxation of strips of canine saphenous vein and tibial artery when they had been contracted by nerve stimulation than by exogenous norepinephrine. An infusion of adenosine into the dogs' lateral saphenous vein, perfused at constant flow, caused a greater relaxation of this vein when constricted by electrical stimulation of the lumbar sympathetic chain than by exogenous norepinephrine. That this difference was due to inhibition by these compounds of the output of neurotransmirter from the sympathetic nerve endings was demonstrated by column chromatographic analysis of the radioactivity in the supervision fluid of vein strips, previously incubated with tritiated norepinephrine. Both adenosine and adenosine triphosphate (10"' M) reduced the efflux of 3 H-norepinephrine during nerve stimulation with electrical impulses. Adenosine also reduced the efflux caused by potassium (30 mM), but not that caused by tyramine (6 x 10~6 M). Theophylline antagonized the inhibitory effect of adenosine on the sympathetic neurotransmission. We found that at 4 x 10 4 M adenosine triphosphate still caused a decreased efflux of neurotransmitter during electrical stimulation, but with adenosine the 3 H-norepinephrine efflux no longer decreased and the overflow of deaminated compounds increased. Furthermore, the same concentration of adenosine increased the efflux of 3 H-norepinephrine and deaminated compounds in unstimulated strips, and the increase of 3 H-norepinephrine was enhanced after monoamine oxidase inhibition. Thus, we conclude that at higher concentrations adenosine increases the intraneuronal leakage of norepinephrine out of the storage vesicles.ADENOSINE and the adenine nucleotides by a local action on blood vessels cause their dilation. This has been demonstrated both in vivo and in vitro. '" 3 There is evidence that these substances can inhibit neuromuscular transmission in the rat phrenic nerve-diaphragm and frog sartorius preparations 4 ' 5 and cholinergic neurotransmission in the intestinal wall. 6 The present experiments were performed to determine whether adenosine and related nucleotides inhibit adrenergic neurotransmission in canine blood vessels.
Methods
STUDIES IN VITROHelical strips of lateral saphenous veins and anterior tibial arteries, isolated from dogs (15-25 kg) anesthetized with sodium pentobarbital (30 mg/kg, iv), were placed in an organ bath filled with Krebs-Ringer solution (NaCl, 118.2 mM; KC1, 4.7 mM; MgSO 4 , 1.2 mM; KH 2 PO 4 , 1.2 mM; CaCl 2 , 2.5 mM; NaHCO 3 , 25 mM; calcium disodium ethylenediaminetetraacetate (EDTA) 0.026 mM; and glucose, 5.5 mM) maintained at 37°C and aerated with a 95% O 2 -5% CO 2 mixture. The strips were attached to a force transducer (Grass FT 03C) for isometric tension recording. The transducer was mounted on a movable support allowing fine adjustments of the strip length and connected to a pen writing recorder (Gould Brush 220). For electrical stimulation of the preparations, two rectangular platinum electr...