Klinische Wochenschrift

, Volume 62, Issue 15, pp 717–723 | Cite as

Negative inotropic effects of aldosterone antagonists in isolated human and guinea-pig ventricular heart muscle

  • A. Mügge
  • W. Schmitz
  • H. Scholz


The effects of K+-canrenoate (Aldactone® pro inj.) and its metabolite canrenone on isometric force of contraction were measured in isolated guinea-pig and human papillary muscle preparations driven electrically at a frequency of 1 Hz. In guinea-pig hearts both substances exerted a concentration-dependent negative inotropic effect; the IC50 of K+-canrenoate and canrenone were 129±22 µmol l−1 (n=5) and 85±11 µmol l−1 (n=12), respectively. At the maximally tested concentration canrenone (250 µmol l−1) and K+-canrenoate (1,000 µmol l−1) reduced force of contraction by 68±4% (n=12) and 83±3% (n=5), respectively. The negative inotropic effects of canrenone and K+-canrenoate were not affected by 10 µmol l−1 atropine. The negative inotropic effect of canrenone was also not affected by 14 µmol l−1 aldosterone, but canrenone (10 µmol l−1) diminished the maximal positive inotropic effect of dihydro-ouabain from 554±75% (n=4) to 269±39% (n=4) of the predrug value.

In human heart muscles K+-canrenoate and canrenone also exerted a concentration-dependent negative inotropic effect. K+-canrenoate (1,000 µmol l−1) and canrenone (250 µmol l−1) reduced force of contraction by 57±7% (n=8) and 67±2% (n=6), respectively. A positive inotropic effect of both substances was never observed.

It is concluded that the improvement of cardiac performance after application of aldosterone antagonists observed in patients cannot be explained by a direct effect on the heart. K+-canrenoate and canrenone are devoid of any direct cardiotonic action. Instead, K+-canrenoate and canrenone have direct negative inotropic effects at high concentrations.

Key words

Aldosterone antagonists Canrenone K+-canrenoate Negative inotropic effect Human heart 


Aldactone® pro inj

Aldactone® pro injection






concentration of drugs which produce 50% inhibition of force of contraction







mm s−1

millimeter per second

mmol l−1





milli newton



SC 8109

spironolactone derivative


standard error of the mean




volume per volume

µmol l−1



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Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • A. Mügge
    • 1
  • W. Schmitz
    • 1
  • H. Scholz
    • 1
  1. 1.Abteilung Allgemeine PharmakologieUniversitäts-Krankenhaus Eppendorf, Universität HamburgGermany

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