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.
Lund
C O
CO
Department of Obstetrics and Gynecology, Hvidovre University Hospital, Copenhagen, Denmark.
Nilas
L
L
Dalsgaard
T
T
Pedersen
S H
SH
Ottesen
B
B
D000818:Animals; D019540:Area Under Curve; D001921:Brain / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007536:Isomerism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009652:Norpregnenes / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D011897:Random Allocation; D019789:Tetraethylammonium / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D014666:Vasomotor System / Q000187:drug effects
D009652:Norpregnenes; D014665:Vasodilator Agents; D004958:Estradiol; D019789:Tetraethylammonium; C027385:tibolone; D011188:Potassium; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester