Acute actions of 3 alpha-hydroxy-tibolone on factors influencing contraction in guinea-pig ventricular myocytes.
We investigated whether one of the main estrogenic metabolites of the postmenopausal agent, tibolone (Org OD14), exerts direct cardiac actions in a similar way to 17beta-estradiol. 3alpha-OH-tibolone (40 microM) decreased both cell shortening and Ca2+ transient amplitude of field-stimulated (1 Hz, 37 degrees C) guinea-pig ventricular myocytes. These effects were still observed in cells that had been incubated with the specific estrogen receptor antagonist, ICI 182,780 (C(32)H(47)F(5)O(3)S), suggesting an estrogen receptor-independent mechanism of action. In addition, 3alpha-OH-tibolone inhibited the L-type Ca2+ current and shortened action potential durations (APD). This mechanism may contribute to a potential cardiovascular action of tibolone.
Liew
Reginald
R
Cardiac Medicine, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK. r.liew@imperial.ac.uk
Stagg
Mark A
MA
MacLeod
Kenneth T
KT
Collins
Peter
P
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D009652:Norpregnenes / Q000494:pharmacology*; D016276:Ventricular Function
C485705:3-hydroxytibolone; D009652:Norpregnenes