title: Oestrogen relaxes human epicardial coronary arteries through non-endothelium-dependent mechanisms.
abstract: BACKGROUND
  Oestrogen-replacement therapy is associated with a reduced incidence of cardiovascular disease. The acute administration of oestrogen improves myocardial ischemia in women with coronary heart disease. In this study we investigated the relaxing effect of oestradiol-17 beta on human coronary arteries in vitro and determined the role of endothelial modulation in this relaxation by using isolated human coronary arteries.
  
  
  METHODS
  Atherosclerosis-free epicardial arteries from men and women were removed from patients undergoing heart or combined heart and lung transplantation. The arteries were cut into ring segments and placed into organ baths containing Tyrode's solution. Changes in isometric tension were measured. The relaxing response to oestradiol-17 beta (10(-10) - 10(-5) mol/l) was investigated and the effects of endothelium, NGmonomethyl-L-arginine and indomethacin on the response of oestradiol-17 beta were assessed.
  
  
  RESULTS
  Oestradiol-17 beta (10(-10) - 10(-5) mol/l) induced significant relaxation in coronary arteries pre-contracted with the thromboxane A2 analog (U46619; 3 x 10(-8) mol/l). Relaxation was significantly greater in coronary arteries from female patients. No significant differences were observed between arteries with or without endothelium nor after nitric oxide synthase or cyclo-oxygenase inhibition. These results indicate that oestradiol-17 beta induces human coronary artery relaxation via an endothelium-independent mechanism in vitro. The sex of the patients significantly affects sensitivity of the coronary arterial rings to oestrogen.
  
  
  CONCLUSIONS
  Oestradiol-17 beta-induced coronary relaxation may play an important role in regulation of coronary tone, and may partly explain why oestrogen improves myocardial ischemia in women and why it protects postmenopausal women from the risk of developing coronary heart disease.
authors.affiliation: Department of Cardiothoracic Surgery, National Heart and Lung Institute, Harefield Hospital, UK.
authors.forename: A H
authors.initials: AH
authors.lastname: Chester
authors.forename: C
authors.initials: C
authors.lastname: Jiang
authors.forename: J A
authors.initials: JA
authors.lastname: Borland
authors.forename: M H
authors.initials: MH
authors.lastname: Yacoub
authors.forename: P
authors.initials: P
authors.lastname: Collins
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000293:Adolescent; D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007223:Infant; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000517:prevention & control; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D012737:Sex Factors; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine
chemical_list: D004791:Enzyme Inhibitors; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D019323:omega-N-Methylarginine; D004958:Estradiol; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001120:Arginine; D007213:Indomethacin