HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 295/5/H1935    most recent 00723.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Gui, Y. Articles by Walsh, M. P. PubMed PubMed Citation Articles by Gui, Y. Articles by Walsh, M. P.

Inhibition of rat aortic smooth muscle contraction by 2-methoxyestradiol

Smooth Muscle Research Group, Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada

Submitted 14 July 2008 ; accepted in final form 3 September 2008

Recent studies suggest that 2-methoxyestradiol (2-ME), an estrogen metabolite, has a similar inhibitory effect as 17β-estradiol (E₂) on vascular tone. However, it is not known whether 2-ME mediates the effects of E₂ or by what mechanism 2-ME regulates smooth muscle contraction. Therefore, we compared the effects of 2-ME and E₂ on rat aortic smooth muscle contraction. A preincubation with 2-ME (10 µM) for 1 h inhibited phenylephrine (PE)-induced tension in endothelium-intact, but not -denuded, tissues, whereas E₂ inhibited PE-induced contraction in both preparations. The effects of 2-ME and E₂ on endothelium-intact preparations were prevented by L-NAME hydrochloride (a nitric oxide synthase inhibitor). The 2-ME treatment reduced PE-induced phosphorylation of the 20-kDa myosin regulatory light chain. The inhibitory effects of 2-ME and E₂ were not affected by ICI-182780 (an estrogen receptor antagonist) or actinomycin D (a gene transcription inhibitor); however, the effect of 2-ME, but not E₂, was prevented by cycloheximide (a protein synthesis inhibitor). Furthermore, the effect of E₂ was not blocked by 1-aminobenzotriazole (a cytochrome P-450 inhibitor) or Ro 41-0960 (a catechol-O-methyltransferase inhibitor). The effect of 2-ME was not mimicked by microtubule-interfering agents (nocodazole or Taxol). We conclude that 2-ME inhibits smooth muscle contractility through an endothelium- and nitric oxide-dependent mechanism, which does not involve estrogen receptors or microtubule disruption. The effect of 2-ME, but not E₂, involves de novo protein synthesis. 2-ME does not mediate the inhibitory effect of E₂ on smooth muscle contraction. These results support a potentially important role of 2-ME in the regulation of smooth muscle tone in the vasculature.

17β-estradiol