Brender, D

Acetylstrophanthidin, 0.3 to 10 µg/ml, caused contraction of helical strips of the dog cutaneous vein in an organ bath at 37°C. A latent period of 12 to 60 minutes preceded the contraction. During this time, the vein exhibited a progressive increase in response to transmural electric stimulation and added norepinephrine. As the dose of acetylstrophanthidin was increased, the latent period shortened and the increased response during the latent period was potentiated. When the contraction caused by 10 µg/ml was maximal, no additional contraction occurred with electric stimulation; the response to electric stimulation was only partially restored by the repeated washing out of the drug, despite relaxation of the strip to almost base-line tension. Since transmural electric stimulation causes contraction by release of tissue catecholamines, these experiments demonstrate that digitalis glycosides sensitize the cutaneous veins of the dog to adrenergic stimulation. This was confirmed in dogs anesthetized with pentobarbital. Intravenous injections of acetylstrophanthidin and digoxin, in doses too small (12.5 to 15.5 µ/kg) to cause direct constriction of the lateral saphenous vein, potentiated the constriction of this vein caused by electric stimulation of the lumbar sympathetic chain.

Acetylstrophanthidin, 1.0 to 10.0 µg/ml, caused contraction of strips of the lateral saphenous vein of the dog in an organ bath at 37°C. The superior mesenteric vein, which exhibited spontaneous activity in the organ bath, responded to acetylstrophanthidin with an almost immediate increase in tension and an increased frequency of contractions; this was followed by a sustained contraction which had the same time lag as the contraction of a saphenous vein strip from the same dog. In strips from both veins, the contraction was depressed by cooling and augmented by warming, an effect opposite to that seen with norepinephrine-induced contractions. A latent period of 10 to 60 minutes preceded the contraction of the saphenous vein; during this time, the vein showed increased reactivity to added norepinephrine, 5-hydroxytryptamine, acetylcholine, barium chloride, increased bath concentration of K + , and decreased bath concentration of Na + . The increased reactivity and contraction still occurred after catecholamine depletion of the vein by chronic lumbar sympathectomy and in umbilical veins, which are devoid of adrenergic nerves. In addition to its direct constrictor action on cutaneous and mesenteric veins, acetylstrophanthidin sensitized cutaneous veins to vasoactive agents and to changes in ionic environment. These actions did not depend on the presence of norepinephrine in the veins.