Non Effectiveness of Ouabain and Decrease in Na+/K+ -ATPase Affinity for Ouabain in Failing Rabbit Heart
Impaired mechanical perfomance is me usual cause of Congestive Heart Failure (CHF) (2,10). For this reason, digitalis drugs are still the oldest compounds to treat CHF and still remain the mainstay of treatment despite the advent of new inotropes and vasodilators (9). Multiple changes are described in the failing myocardium such as a downregulation of β adrenoreceptors, a deficient production in cAMP, a decrease in the function of the sarcoplasmic reticulum, an inhibition in the Na+/Ca+ +-exchange leading to excessive calcium accumulation (2,5,6,10). Several studies have examined the Na+/K+-pump in failing hearts but their conclusions are divergent (1,2,7,11). Some of these discrepancies could be due to the experimental model of heart failure, the utilized mammalian species and enzyme assay using pure sarcolemmal membrane fractions with low recovery.
KeywordsATPase Activity Deficient Production Ouabain Binding Site Nonnal Heart Failure Ventricular Cardiac Muscle
Unable to display preview. Download preview PDF.
- 1.Charlemagne D, Maixent JM, Preteseille M, Lelièvre LG (1986) Ouabain binding sites and Na+,K+-ATPase activity in rat cardiac hypertrophy. J Bioch Chem 261: 185–189.Google Scholar
- 2.De Pover A, Grupp G, Schwartz A, Grapp IL (1991) Coupling of contraction through effects on Na+,K+-ATPase: Changes of Na+,K+-ATPase isoforms in heart desease? Heart failure 1: 201–258.Google Scholar
- 3.Dhalla NS, Dixon IMC, Rupp H, Barwinsky J (1991) Experimental congestive heart failure due to myocardial infarction. Sarcolemmal receptors and cation transporters. Current Topics in Heart Failure, 13–23.Google Scholar
- 4.Disow LMG, Hata T, Dhalla MS (1992) Sarcolemmal Na+,K+-ATPase activity in congestive heart failure due to myocardial infarction. Am J Physiol 262: C664–C671.Google Scholar
- 6.Gerbi A, Maixent JM, Zerouga M, Bourre JM (This issue) Heterogenous Na+ sensitivity of Na+,K+-ATPase isoenzymes in membranes; Modulation by anaesthesia and diets.Google Scholar
- 9.Maixent JM, Fénard S, Kawamoto RM (1991) Tissue localization of active Na,K-ATPase isoenzymes by determination of three profiles of inhibition with ouabain, digoxin, digitoxigenin and LND-796, a new aminosteroid cardiotonic. J Receptor Res 11: 687–698Google Scholar
- 10.Paganelli F, Gerbi A, Barbey O, Maixent JM, Lαvy S (1993) Bases pharmacologiques et cliniques de l’emploi des b-bloquants (β1 et/ou β2 spécifiques) dans l’insuffisance cardiaque. JAMA Suppl Août 4–16Google Scholar