Acute effects of tibolone on cerebral vascular reactivity in vitro.

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, 3alpha-OH-tibolone, 3beta-OH-tibolone, Delta(4) isomer and 17beta-estradiol were obtained before and after addition of the NO blocker N(omega)-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 17beta-estradiol (area under the curve (AUC); tibolone vs. 17beta-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 17beta-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 17beta-estradiol, and seems to be mediated by inhibition of voltage-gated calcium channels and possibly partly by a nitric oxide-dependent mechanism.