ROLE OF THE SUGAR TRANSPORT SYSTEM IN THE POSITIVE INOTROPIC RESPONSE TO DIGITALIS

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 176; no. 3; pp. 538 - 544
• Main Authors: Bailey, L E, Dresel, P E
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.03.1971
• Subjects: Animals; Biological Transport - drug effects; Carbohydrates - pharmacology; Cardanolides - pharmacology; Diabetes Mellitus, Experimental - physiopathology; Electric Stimulation; Female; Heart - drug effects; Heart Atria - drug effects; In Vitro Techniques; Insulin - pharmacology; Male; Muscle Contraction - drug effects; Ouabain - pharmacology; Phloretin - pharmacology; Rabbits
• ISSN: 0022-3565; 1521-0103

We reported previously that purified insulin increased the rate of onset of the positive inotropic response to ouabain. Other studies suggest that the changes in the positive inotropic response caused by insulin and other agents which affect sugar uptake may be mediated by alterations in the transport or the fixation of the cardiac glycosides in the cell. We have now investigated the interactions between the cardiac glycosides and various agents which affect membrane transport in cardiac muscle. Left atria obtained from mixed breed rabbits were bathed in Krebs-Henseleit solution at 30°C and stimulated electrically at 2/sec. Ouabain did not affect contractility in atria bathed in a substrate-free medium, or in a solution containing substrates other than glucose, and insulin did not permit an effect to develop under these conditions. Phioretin, in a concentration known to block sugar transport but not metabolic processes, prevented the development of the positive inotropic response to ouabain. This blockade was not reversed by insulin. Atria removed from rabbits made diabetic by alloxan responded initially to ouabain with a normal positive inotropic response, but this response was not maintained unless 2 mU/ml of purified insulin was present in the bath. κ-Strophanthidin, the aglycone of ouabain, did not increase the strength of contraction in glucose medium but had a significant positive inotropic response after the atria were pretreated with purified insulin. The results suggest that sugar transport and metabolism are required for the initiation of the positive inotropic response to the cardiac glycosides.