title: 17 beta-Estradiol inhibits Ca2+ influx and Ca2+ release induced by thromboxane A2 in porcine coronary artery.
abstract: BACKGROUND
  We wished to investigate the possible mechanism of the protective effect of estrogen replacement on coronary atherosclerosis observed in postmenopausal women.
  
  
  RESULTS
  Cytosolic Ca2+ concentration ([Ca2+]i) and contraction were measured simultaneously in fura 2-loaded porcine coronary arterial strips stimulated by the thromboxane A2 analogue U46619 and high-K+ depolarization in the presence and absence of 17 beta-estradiol. Pretreatment with 17 beta-estradiol (30 nmol/L to 30 mumol/L) inhibited the sustained elevation of [Ca2+]i and the sustained contraction induced by 300 nmol/L U46619. Higher concentrations of 17 beta-estradiol (1 to 100 mumol/L) also inhibited the U46619-induced transient increase in [Ca2+]i and contraction in the absence of extracellular Ca2+. In the strips precontracted by 90 mmol/L K+, 17 beta-estradiol (30 mumol/L) inhibited the increases in [Ca2+]i and contraction to resting levels. In contrast, 30 mumol/L 17 beta-estradiol only partially inhibited the U46619-induced sustained contraction, despite complete inhibition of the sustained increase in [Ca2+]i. Verapamil (10 mumol/L) also strongly inhibited the sustained increase in [Ca2+]i induced by 300 nmol/L U46619, with a partial inhibition of the U46619-induced sustained contraction. A subsequent addition of 30 mumol/L 17 beta-estradiol did not show an additional inhibitory effect on either the [Ca2+]i or the tension after the addition of verapamil. 17 beta-Estradiol (10 mumol/L) also inhibited the increase in [Ca2+]i and the contraction induced by cumulative addition of Ca2+ in the strips pretreated with 90 mmol/L K+. However, 17 beta-estradiol did not change the slope of the [Ca2+]i-tension curves. 17 beta-Estradiol (10 mumol/L) had no effect on the levels of cAMP and cGMP in the coronary strips.
  
  
  CONCLUSIONS
  17 beta-Estradiol inhibits the contraction of coronary vascular smooth muscle mainly inhibiting Ca2+ influx without changing Ca2+ sensitivity of contractile elements. The Ca2+ channel blocker-like action of 17 beta-estradiol may explain at least a part of the antiatherosclerotic effect of estrogen.
authors.affiliation: Department of Geriatrics, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: S Z
authors.initials: SZ
authors.lastname: Han
authors.forename: H
authors.initials: H
authors.lastname: Karaki
authors.forename: Y
authors.initials: Y
authors.lastname: Ouchi
authors.forename: M
authors.initials: M
authors.lastname: Akishita
authors.forename: H
authors.initials: H
authors.lastname: Orimo
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D011188:Potassium / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D013552:Swine; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D004958:Estradiol; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011188:Potassium; D002118:Calcium