Skip to main content
Log in

Inotropic effect of ouabain in hypertrophied rat heart

  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Abstract

The contribution of the heterogeneous digitalis receptors to the inotropic effect of ouabain was studied in hypertrophied rat hearts (aortic stenosis) by using isolated Langendorff heart preparations. Development and washout of the biological effects as well as the dose/ response curves revealed two inotropic components of high and low drug sensitivity. Maximal inotropy was observed with 100 μM ouabain in both control and hypertrophied rat hearts. The high-sensitivity component accounted for only one-third of the response in control hearts but for two-thirds in hypertrophied hearts. The respective apparent affinities (10–20 nM and 10–20 μM) of the two inotropic components found in isolated hearts were similar to those of the high- and low-affinity Na+,K+-ATPase activities detected in isolated cardiac sarcolemma. Onset and reversion of the pharmacological effects of ouabain occurred at respective rates that were similar to those of the association and dissociation of ouabain to the Na+,K+-ATPase level. In hypertrophied heart, the high- and low-sensitivity components (or receptors) reacted seven- and threefold, respectively, more slowly than the corresponding sites in normal hearts. These alterations in inotropic responsiveness and propertries of the digitalis receptors in cardiac hypertrophy suggest that new regulations should be taken into account in the adaptation to pressure overload.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adams RJ, Schwartz A, Grupp G, Grupp I, Lee SW, Wallic ET, Powell T, Twist VW, Gathiram P (1982) High-affinity ouabain site and low-dose positive inotropic effect in rat myocardium. Nature 296:167–169

    Google Scholar 

  • Akera T, Ng YC, Hadley R, Katano Y, Brody TM (1986) High affinity and low affinity ouabain binding sites in the rat heart. Eur J Pharmacol 132:137–146

    Google Scholar 

  • Berrebi-Bertrand I, Maixent JM, Christé G, Lelièvre LG (1990) Two active Na+/K+-ATPase of high affinity for ouabain in adult rat brain membranes. Biochim Biophys Acta 1021:148–156

    Google Scholar 

  • Bevington PR (1969) Data reduction and error analysis for the physical sciences. McGraw Hill, New York

    Google Scholar 

  • Charlemagne D, Maixent JM, Preteseille M, Lelièvre LG (1986) Ouabain-binding sites and (Na+,K+)-ATPase activity in rat cardiac hypertrophy. Expression of the neonatal forms. J Biol Chem 261:185–189

    Google Scholar 

  • Charlemagne D, Mayoux E, Poyard M, Oliviero P, Geering K (1987) Identification of two isoforms of the catalytic subunit of Na,K-ATPase in myocytes from adult rat heart. J Biol Chem 262:8941–8943

    Google Scholar 

  • Chevalier B, Mouas Ch, Mansier P, Aumont MC, Swynghedauw B (1986) Screening of inotropic drugs on isolated rat and guinea pig hearts. J Pharmacol Methods 17:313–326

    Google Scholar 

  • Chevalier B, Berrebi-Bertrand I, Mouas Ch, Lelièvre LG, Swynghedauw B (1989) Diminished toxicity of ouabain in the hypertrophied rat heart. Pflügers Arch 414:311–316

    Google Scholar 

  • Ebner F, Siegl H (1988) Diffusion characteristics dissociate ouabain binding from inotropic effect in guinea-pig myocardium. Br J Pharmacol 95:399–404

    Google Scholar 

  • Erdmann E, Philipp G, Scholz H (1980) Cardiac glycoside receptors, (Na+,K+)-ATPase activity and force of contraction in rat heart. Biochem Pharmacol 29:3219–3229

    Google Scholar 

  • Finet M, Godfraind T, Noël F (1983) The inotropic effect of ouabain and its antagonism by dihydroouabain in isolated rat atria and ventricles in relation to specific binding sites. Br J Pharmacol 80:751–759

    Google Scholar 

  • Grupp IL, Grupp G, Schwartz A (1981) Digitalis receptor desensitization in rat ventricle: ouabain produces two inotropic effects. Life Sci 29:2789–2794

    Google Scholar 

  • Grupp G, De Pover A, Grupp IL, Schwartz A (1984) Analysis of the inotropic action of ouabain in rat ventricles: two apparent ouabain inotropic responses. Proc Soc Exp Biol Med 175: 39–43

    Google Scholar 

  • Grupp IL, Im WB, Lee SW, Pecker MS, Schwartz A (1985) Relation of sodium pump inhibition to positive inotropic at low concentrations of ouabain in rat heart muscle. J Physiol (Lond) 360:149–160

    Google Scholar 

  • Herzig S, Mohr K (1984) Action of ouabain on rat heart. Comparison with its effect on guinea-pig heart. Br J Pharmacol 82:135–142

    Google Scholar 

  • Hickerson TW, Grupp IL, Schwartz A, Grupp G (1988) The calcium dependence of the biphasic inotropic response to ouabain in the isolated rat heart. In: Membrane biophysics: III. Biological transports. Liss, New York, pp 223–234

    Google Scholar 

  • Khattner JC, Hoeschen RJ (1984) Reduced number of digitalis receptor sites in the hypertrophied pig myocardium. Basic Res Cardiol 79:396–401

    Google Scholar 

  • Lelièvre LG, Maixent JM, Charlemagne D, Swynghedauw B (1985) Rat cardiac hypertrophy: contribution of heterogeneous digitalis receptor forms. In: Erdmann E, Greeff K, Skou JC (eds) Cardiac glycosides 1785–1985. Springer, New York, pp 87–92

    Google Scholar 

  • Lelièvre LG, Charlemagne D, Mouas Ch, Swynghedauw B (1986a) Respective involvements of high- and low-affinity digitalis receptors in the inotropic response of isolated rat heart to ouabain. Biochem Pharmacol 35:3449–3455

    Google Scholar 

  • Lelièvre LG, Maixent JM, Lorente P, Mouas Ch, Charlemagne D, Swinghedauw B (1986b) Prolonged responsiveness to ouabain in hypertrophied rat heart: physiological and biochemical evidence. Am J Physiol 251:H923-H931

    Google Scholar 

  • Mansier P, Lelièvre LG (1982) Ca2+-free perfusion of rat heart reveals a (Na+,K+)-ATPase form highly sensitive to ouabain. Nature 300:535–537

    Google Scholar 

  • Nirasawa Y, Akera T (1987) Pressure-induced cardiac hypertrophy: changes in Na+,K+-ATPase and glycoside actions in cats. Eur J Pharmacol 137:77–83

    Google Scholar 

  • Noël F, Godfraind T (1984) Heterogeneity of ouabain specific binding sites and (Na+,K+)-ATPase inhibition in microsomes from rat heart. Biochem Pharmacol 33:47–53

    Google Scholar 

  • Schwartz A, Whitmer K, Grupp G, Grupp IL, Adams RJ, Lee SW (1982) Mechanism of action of digitalis: is the Na,K-ATPase the pharmacological receptor? Ann NY Acad Sci 402:253–271

    Google Scholar 

  • Sweadner KJ, Farshi SK (1987) Rat cardiac ventricle has two Na+,K+-ATPases with different affinities for ouabain: developmental changes in immunologically different catalytic subunits. Proc Natl Acad Sci USA 84:8404–8407

    Google Scholar 

  • Wellsmith NV, Lindenmayer GE (1980) Two receptor forms for ouabain in sarcolemma-enriched preparations from canine ventricle. Circ Res 47:710–720

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Berrebi-Bertrand, I., Lelièvre, L.G., Mouas, C. et al. Inotropic effect of ouabain in hypertrophied rat heart. Pflugers Arch. 417, 247–254 (1990). https://doi.org/10.1007/BF00370988

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00370988

Key words

Navigation