Inhibition of adrenergic neurotransmission in isolated veins of the dog by potassium ions

Abstract

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. Helical strips cut from dogs' saphenous veins were incubated in Krebs Ringer solution containing [7 3H]norepinephrine (5 x 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. 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 10, 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. Addition of tyramine (4 x 10-6 g/ml. min) to the superfusate augmented both the tension and the efflux, but these actions were not depressed by increasing the K+ concentration. Cocaine, phentolamine, and phenoxybenzamine did not prevent the depression by K+ of the response to electric stimulation. 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. 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 equiv/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. In higher concentrations (40 m equiv/l.), K+ caused both a liberation of norepinephrine and a direct activation of the smooth muscle cells.