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Hill BJ, Gebre S, Schlicker B, Jordan R, Necessary S: Nongenomic inhibition of coronary constriction by 17beta-estradiol, 2-hydroxyestradiol, and 2-methoxyestradiol. Can J Physiol Pharmacol. 2010 Feb;88(2):147-52.
The cardioprotective effects of 17beta-estradiol (E2) in women are hypothesized to be partially mediated by the E2 metabolites 2-hydroxyestradiol (2-HOE) and 2-methoxyestradiol (2-MeOH). Therefore, the purpose of our study was to determine the acute effects of E2, 2-HOE, and 2-MeOH on inhibition of coronary arterial constriction. Right coronary arteries obtained from breeding sows were cut into 4 mm rings and suspended in organ baths. Incubation of the rings with E2, 2-HOE, and 2-MeOH (10 micromol/L) for 60 min attenuated a subsequent KCl-induced contraction by approximately 50%. The protein synthesis inhibitor cycloheximide and the estrogen receptor antagonists ICI 182780 and tamoxifen did not affect the attenuation. Moreover, E2, 2-HOE, and 2-MeOH antagonized the contraction induced by the vasospasm agonist endothelin-1 (0.1 micromol/L) by approximately 36%. When the L-type Ca2+ channel blocker nifedipine was added at the conclusion of the experiment, no additional contractile attenuation was present. Our results suggest that E2, 2-HOE, and 2-MeOH demonstrate a similar nongenomic inhibition of agonist-induced extracellular Ca2+-dependent contractions. |
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