Abstract
Objectives: To compare the acute effects of estradiol, tibolone and its metabolites on coronary
arteries in vitro and to investigate possible vascular mechanisms. Methods: Coronary artery ring segments from female rabbits were mounted in myographs for isometric
tension recordings. Concentration–response curves to tibolone, 3α-OH-tibolone, 3β-OH-tibolone,
Δ4-isomer and 17β-estradiol were obtained after precontraction with potassium 30 mmol/l and after addition of Nω-nitro-l-arginine methyl ester 10−4 mol/l (l-NAME, an inhibitor of endothelial nitric oxide (NO) synthase) or tetraethylammonium
chloride 10−2 mol/l (TEA, an unspecific inhibitor of potassium channels). The effects of the different
substances to calcium concentration–response curves were evaluated. Responses are
expressed as maximal contraction (Emax), concentration giving half maximal contraction (log EC50) or area under curve (AUC). Results: Tibolone and its metabolites induced a concentration-dependent vasodilatation comparable
to that of 17β-estradiol with the rank of potency: 3β-OH-tibolone ≅ tibolone > 3α-OH-tibolone
> Δ4-isomer (ANOVA). l-NAME partly inhibited the relaxation to all substances. TEA induced a slight rightward
shift of the relaxation to 3α-OH-tibolone (log EC50: −5.05 versus −5.20; P<0.05; Student’s t-test), but not to the other substances. Calcium concentration-dependent contraction
curves were inhibited by all substances compared to controls (AUC, P<0.05, ANOVA). Conclusions: Our data indicate that the acute relaxation induced by tibolone and its metabolites
in coronary arteries in vitro are probably mediated by endothelium independent inhibition
of calcium channels but may also involve an endothelium-dependent mechanism via nitric
oxide. The effect of tibolone is comparable to that of 17β-estradiol in this set-up.
Keywords
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Article info
Publication history
Accepted:
January 15,
2004
Received in revised form:
October 30,
2003
Received:
January 3,
2003
Identification
Copyright
© 2004 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
