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Inhibition of adrenergic neurotransmission in isolated veins of the dog by potassium ions.
Author(s) -
Lorenz R R,
Vanhoutte P M
Publication year - 1975
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1975.sp010900
Subject(s) - phentolamine , medicine , norepinephrine , phenoxybenzamine , chemistry , endocrinology , stimulation , efflux , tyramine , adrenergic , neurotransmission , potassium , propranolol , biology , receptor , biochemistry , dopamine , organic chemistry
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.