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• W1966706075 endingPage "H1942" @default.
• W1966706075 startingPage "H1935" @default.
• W1966706075 abstract "Recent studies suggest that 2-methoxyestradiol (2-ME), an estrogen metabolite, has a similar inhibitory effect as 17β-estradiol (E 2 ) on vascular tone. However, it is not known whether 2-ME mediates the effects of E 2 or by what mechanism 2-ME regulates smooth muscle contraction. Therefore, we compared the effects of 2-ME and E 2 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 E 2 inhibited PE-induced contraction in both preparations. The effects of 2-ME and E 2 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 E 2 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 E 2 , was prevented by cycloheximide (a protein synthesis inhibitor). Furthermore, the effect of E 2 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 E 2 , involves de novo protein synthesis. 2-ME does not mediate the inhibitory effect of E 2 on smooth muscle contraction. These results support a potentially important role of 2-ME in the regulation of smooth muscle tone in the vasculature." @default.
• W1966706075 created "2016-06-24" @default.
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• W1966706075 date "2008-11-01" @default.
• W1966706075 modified "2023-10-03" @default.
• W1966706075 title "Inhibition of rat aortic smooth muscle contraction by 2-methoxyestradiol" @default.
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• W1966706075 doi "https://doi.org/10.1152/ajpheart.00723.2008" @default.
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