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3β-OH-tibolone acutely dilates rat muscle arterioles similar to 3α-OH-tibolone

Korstjens, Iolente J.M. MS1; van der Mooren, Marius J. MD, PhD, MSc2; Kloosterboer, Helenius J. PhD3; Sipkema, Pieter PhD1

doi: 10.1097/gme.0b013e3181407c6b
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In an earlier study, we focused on the vasoactive effect of 3α-OH-tibolone on spontaneously constricted isolatedfemale rat gracilis muscle arterioles. Vasodilator effects (from 10−7 to 10−4 M) of 3α-OH-tibolone were similar to those of 17β-estradiol. It was reported that 3β-OH-tibolone like estradiol altered GABAB activation in neurons through a membrane estrogen receptor, whereas the 3α-OH metabolite did not. We therefore hypothesized that the 3β-OH metabolite may also have a vasodilating effect in our isolated arteriole model. The results indicate that 3β-OH-tibolone induces a vasodilator effect in small arterioles that is comparable with that of 3α-OH-tibolone at the same concentration. This is intriguing because the binding affinity of 3α-OH-tibolone to the estrogen receptor is almost twice that of 3β-OH-tibolone. Other mechanisms may play a role.

Favorable vasodilator effects of 3β-OH-tibolone are observed in isolated small arterioles from skeletal muscle in the rat. This study adds to a better understanding of the nongenomic mechanisms by which metabolites of tibolone modulate vascular responses.

From the Departments of 1Physiology and 2Obstetrics and Gynecology, VU University Medical Center, Amsterdam; 3N.V. Organon, Oss, The Netherlands.

Received February 7, 2007; revised and accepted June 12, 2007.

Funding/support: This work was supported in part by N.V. Organon.

Financial disclosure: Dr. Kloosterboer was an employee of Organon at the time of this investigation.

Address correspondence to: Pieter Sipkema, PhD, Department of Physiology, VU University Medical Center, Vander Boechorsstraat 7, 1081 BT, Amsterdam, The Netherlands. E-mail: p.sipkema@vumc.nl

©2008The North American Menopause Society