Biomaterial Database

Negative inotropic effects of aldosterone antagonists in isolated human and guinea-pig ventricular heart muscle. 1984

A Mügge, and W Schmitz, and 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 mumol l-1 (n = 5) and 85 +/- 11 mumol l-1 (n = 12), respectively. At the maximally tested concentration canrenone (250 mumol l-1) and K+-canrenoate (1,000 mumol 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 mumol l-1 atropine. The negative inotropic effect of canrenone was also not affected by 14 mumol l-1 aldosterone, but canrenone (10 mumol 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 mumol l-1) and canrenone (250 mumol 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.

UI	MeSH Term	Description	Entries
D009200	Myocardial Contraction	Contractile activity of the MYOCARDIUM.	Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D010042	Ouabain	A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like DIGITALIS. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-EXCHANGING ATPASE.	Acocantherin,G-Strophanthin,Acolongifloroside K,G Strophanthin
D002191	Canrenoic Acid	A synthetic pregnadiene derivative with anti-aldosterone activity.	Canrenoate Potassium,Potassium Canrenoate,17-Hydroxy-3-Oxo-17alpha-Pregna-4,6-Diene-21-Carboxylic Acid,Kalium-Can.-Ratiopharm,SC-14266,Soldactone,Soludactone,Spiroctan,17 Hydroxy 3 Oxo 17alpha Pregna 4,6 Diene 21 Carboxylic Acid,Acid, 17-Hydroxy-3-Oxo-17alpha-Pregna-4,6-Diene-21-Carboxylic,Acid, Canrenoic,Canrenoate, Potassium,Kalium Can. Ratiopharm,SC 14266,SC14266
D002192	Canrenone	A synthetic pregnadiene compound with anti-aldosterone activity.	11614 R.P.,Aldadiene,Phanurane,SC-9376,R.P., 11614,SC 9376,SC9376
D004347	Drug Interactions	The action of a drug that may affect the activity, metabolism, or toxicity of another drug.	Drug Interaction,Interaction, Drug,Interactions, Drug
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006352	Heart Ventricles	The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation.	Cardiac Ventricle,Cardiac Ventricles,Heart Ventricle,Left Ventricle,Right Ventricle,Left Ventricles,Right Ventricles,Ventricle, Cardiac,Ventricle, Heart,Ventricle, Left,Ventricle, Right,Ventricles, Cardiac,Ventricles, Heart,Ventricles, Left,Ventricles, Right
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000451	Mineralocorticoid Receptor Antagonists	Drugs that bind to and block the activation of MINERALOCORTICOID RECEPTORS by MINERALOCORTICOIDS such as ALDOSTERONE.	Aldosterone Antagonist,Aldosterone Antagonists,Aldosterone Receptor Antagonist,Mineralocorticoid Antagonist,Mineralocorticoid Receptor Antagonist,Aldosterone Receptor Antagonists,Mineralocorticoid Antagonists,Antagonist, Aldosterone,Antagonist, Aldosterone Receptor,Antagonist, Mineralocorticoid,Antagonist, Mineralocorticoid Receptor,Antagonists, Aldosterone,Antagonists, Aldosterone Receptor,Antagonists, Mineralocorticoid,Antagonists, Mineralocorticoid Receptor,Receptor Antagonist, Aldosterone,Receptor Antagonist, Mineralocorticoid,Receptor Antagonists, Aldosterone,Receptor Antagonists, Mineralocorticoid
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia