3beta-OH-tibolone acutely dilates rat muscle arterioles similar to 3alpha-OH-tibolone.
In an earlier study, we focused on the vasoactive effect of 3alpha-OH-tibolone on spontaneously constricted isolatedfemale rat gracilis muscle arterioles. Vasodilator effects (from 10 to 10 M) of 3alpha-OH-tibolone were similar to those of 17beta-estradiol. It was reported that 3beta-OH-tibolone like estradiol altered GABAB activation in neurons through a membrane estrogen receptor, whereas the 3alpha-OH metabolite did not. We therefore hypothesized that the 3beta-OH metabolite may also have a vasodilating effect in our isolated arteriole model. The results indicate that 3beta-OH-tibolone induces a vasodilator effect in small arterioles that is comparable with that of 3alpha-OH-tibolone at the same concentration. This is intriguing because the binding affinity of 3alpha-OH-tibolone to the estrogen receptor is almost twice that of 3beta-OH-tibolone. Other mechanisms may play a role.
Korstjens
Iolente J M
IJ
Department of Physiology, VU University Medical Center, Amsterdam, The Netherlands.
van der Mooren
Marius J
MJ
Kloosterboer
Helenius J
HJ
Sipkema
Pieter
P
D000818:Animals; D001160:Arterioles / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D005260:Female; D018482:Muscle, Skeletal / Q000098:blood supply; D009650:Norpregnanes / Q000494:pharmacology*; D009652:Norpregnenes / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
C529843:3beta-OH-tibolone; D020847:Estrogen Receptor Modulators; D009650:Norpregnanes; D009652:Norpregnenes; C027385:tibolone