Acute effects of tibolone on cerebral vascular reactivity in vitro

Abstract

Objective: To evaluate the acute effects of tibolone and its metabolites on cerebral vascular reactivity in vitro. Methods: Ring segments of the posterior cerebral artery from female rabbits were mounted in myographs for isometric tension recordings. Concentration-response curves with tibolone, 3α-OH-tibolone, 3β-OH-tibolone, Δ4 isomer and 17β-estradiol were obtained before and after addition of the NO blocker Nω-nitro-L-arginine methyl ester (L-NAME, 10-4 mol/l) or the potassium-channel blocker tetraethylammonium chloride (TEA, 10-2 mol/l). Additionally, the effects of the hormones on the concentration-response curves with calcium were examined. Results: Tibolone and its metabolites induced a concentration-dependent relaxation comparable to that of 17β-estradiol (area under the curve (AUC); tibolone vs. 17β-estradiol: 242 vs. 251; p < 0.05, analysis of variance). L-NAME increased the AUC for all substances compared with controls (p < 0.05, Student's t test), except for 17β-estradiol. Preincubation with TEA induced no changes. The concentration-dependent contraction curves with calcium were shifted rightward by all hormones. Conclusions: The study demonstrates that the acute relaxation induced by tibolone and its metabolites in cerebral arteries in vitro is comparable to that with 17β-estradiol, and seems to be mediated by inhibition of voltage-gated calcium channels and possibly partly by a nitric oxide-dependent mechanism.