Metabolic requirement for the inotropic effects of digitalis and BAY K 8644.
The positive inotropic effects of ouabain and of BAY K 8644 are not apparent in rabbit atria suspended in substrate free medium or in a medium containing 5 mM pyruvate. Addition of glucose in graded concentrations (1-11 mM) during continued exposure of the preparations to the inotropic agents yields graded inotropic effects. The possible involvement of the glycolytic pathway to the development of the inotropic effect of ouabain and BAY K 8644 was tested by using inhibitors of glycolysis that act at two different steps. Iodoacetic acid completely blocks the inotropic effect of ouabain in atria at 0.1 mM and papillary muscles at 0.05 mM. The inotropic effect of BAY K 8644 was blocked partially in atria and papillary muscles. Iodoacetic acid did not change the inotropic effects of isoproterenol and Ca2+. Addition of 1 mM fluoride did not affect significantly the inotropic effect of either ouabain or BAY K 8644 in atria but partially blocked the effect of BAY K 8644 in papillary muscles. The response of atria to ouabain was not changed significantly when glyceraldehyde (10 mM) was substituted for glucose. We suggest that glycolytic ATP may be important for the full inotropic effect of ouabain and BAY K 8644.
Ogbaghebriel
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Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Dresel
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PE
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D004071:Digitalis Glycosides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005260:Female; D005459:Fluorides / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D005985:Glyceraldehyde / Q000494:pharmacology; D006019:Glycolysis / Q000187:drug effects; D066298:In Vitro Techniques; D007461:Iodoacetates / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011817:Rabbits
D004071:Digitalis Glycosides; D007461:Iodoacetates; D005985:Glyceraldehyde; D010042:Ouabain; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D010751:Phosphopyruvate Hydratase; D005947:Glucose; D005459:Fluorides