Inhibition of adrenergic neurotransmission in isolated veins of the dog by potassium ions.
1. In the intact organism, an increase in K+ concentration decreases the reactivity of blood vessels to sympathetic stimulation. The present experiments were designed to determine whether or not K+ interferes with adrenergic neurotransmission. 2. Helical strips cut from dogs' saphenous veins were incubated (4 hr) in Krebs-Ringer solution containing [7-3H]norepinephrine (5 times 10(-8) g/ml). The preparations were mounted for superfusion and isometric tension recording; the superfusate was collected for estimation of total radioactivity and for chromatographic separation of 3H-labelled norepinephrine and metabolites. 3. Supramaximal electric stimulation (5 Hz, 9 V, 2 msec) increased the tension and the [3H]norepinephrine efflux. Increasing the K+ concentration from 5-9 to 1, 15, and 20 m-equiv/l. caused a progressive depression of these contractions and diminished the total 3H efflux in proportion to the relaxation; the decrease in 3H efflux reflected a decrease in intact [3H]norepinephrine. The same increase in K+ concentration did not alter basal tension or basal 3H efflux. 4. Addition of tyramine (4 times 10(-6) g/ml. min) to the superfusate augmented both the tension and the efflux, but these actions were not depresesd by increasing the K+ concentration. 5. Cocaine, phentolamine, and phenoxybenzamine did not prevent the depression by K+ of the response to electric stimulation. 6. These experiments show that K+ causes relaxation of venous smooth muscle constricted by sympathetic stimulation and does so by inhibiting the release of norepinephrine from nerve endings. By contrast, K+ does not inhibit norepinephrine release in response to tyramine. 7. During submaximal electric stimulation (5 Hz, 1-8--3 V, 2 msec), increasing the K+ concentration from 5-9 to 10 and 15 m-equiv/l. potentiated the contractions and increased the [3H]norepinephrine efflux; at 20 m-equil/l, K+ caused transient increases in tension and 3H efflux followed by relaxation and decreased norepinephrine release. After addition of cocaine (10(-5) g/ml. min), K+ only caused relaxation and decrease in 3H efflux, showing that, in addition to inhibition of norepinephrine release, K+ also inhibits the reuptake process. 8. In higher concentrations (40 m-equil/l.), K+ caused both a liberation of norepinephrine and a direct activation of the smooth muscle cells.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D010643:Phenoxybenzamine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D012501:Saphenous Vein / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D014439:Tyramine / Q000494:pharmacology
D010643:Phenoxybenzamine; D003042:Cocaine; D011188:Potassium; D009638:Norepinephrine; D014439:Tyramine; D010646:Phentolamine