Nongenomic inhibition of coronary constriction by 17ß-estradiol, 2-hydroxyestradiol, and 2-methoxyestradiol.
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.
Hill
Brent J F
BJ
Department of Biology, 201 Donaghey Avenue, University of Central Arkansas, Conway, AR 72035, USA. bhill@uca.edu
Gebre
Senetibeb
S
Schlicker
Bonnie
B
Jordan
Renée
R
Necessary
Sean
S
D000077584:2-Methoxyestradiol; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000378:metabolism; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D005260:Female; D016678:Genome / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D002316:Cardiotonic Agents; D004958:Estradiol; D000077584:2-Methoxyestradiol; C001390:2-hydroxyestradiol; D002118:Calcium