Linked Life Data

18775847

Source:http://linkedlifedata.com/resource/pubmed/id/18775847

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-11-10
pubmed:abstractText
Recent studies suggest that 2-methoxyestradiol (2-ME), an estrogen metabolite, has a similar inhibitory effect as 17beta-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 microM) 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0363-6135
pubmed:author
pubmed:issnType
Print
pubmed:volume
295
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H1935-42
pubmed:meshHeading
pubmed-meshheading:18775847-Animals, pubmed-meshheading:18775847-Aorta, pubmed-meshheading:18775847-Endothelium, Vascular, pubmed-meshheading:18775847-Enzyme Inhibitors, pubmed-meshheading:18775847-Estradiol, pubmed-meshheading:18775847-Female, pubmed-meshheading:18775847-Male, pubmed-meshheading:18775847-Muscle, Smooth, Vascular, pubmed-meshheading:18775847-Myosin Light Chains, pubmed-meshheading:18775847-Nitric Oxide, pubmed-meshheading:18775847-Phenylephrine, pubmed-meshheading:18775847-Phosphorylation, pubmed-meshheading:18775847-Protein Biosynthesis, pubmed-meshheading:18775847-Rats, pubmed-meshheading:18775847-Rats, Sprague-Dawley, pubmed-meshheading:18775847-Receptors, Estrogen, pubmed-meshheading:18775847-Signal Transduction, pubmed-meshheading:18775847-Transcription, Genetic, pubmed-meshheading:18775847-Tubulin Modulators, pubmed-meshheading:18775847-Vasoconstriction, pubmed-meshheading:18775847-Vasoconstrictor Agents
pubmed:year
2008
pubmed:articleTitle
Inhibition of rat aortic smooth muscle contraction by 2-methoxyestradiol.
pubmed:affiliation
Smooth Muscle Research Group, Department of Biochemistry and Molecular Biology, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta, T2N 4N1 Canada.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, Non-U.S. Gov't