Acute effects of 17 beta-oestradiol on functional activity of endothelin-converting enzymes in human arteries and veins.
In this study, we investigated the short-term effect of 17 beta-oestradiol on functional enzyme activity (FEA) of endothelin-converting enzymes in vitro using human internal mammary arteries (n=7-8) and human saphenous veins (n=16-17) obtained from patients undergoing coronary artery bypass graft surgery. Vascular rings were preincubated with either solvent control (0.2% ethanol) or 17 beta-oestradiol (1 microM) for 30 min and concentration-response curves to big ET-1 (0.1-100 nM) or ET-1 (0.1-100 nM) were performed. FEA for each concentration was calculated as the percentage activity [(contraction to big ET-1/contraction to ET-1)x100] normalized to KCl (100 mM). In control experiments, at low concentrations FEA was lower in internal mammary arteries than in saphenous veins (P<0.05). While FEA was suppressed in saphenous veins by 10 nM (4+/-1 versus 22+/-5%, P<0.01) and 30 nM (26+/-4 versus 48+/-7%, P<0.05) 17 beta-oestradiol, FEA was markedly enhanced in internal mammary arteries by 10 nM (33+/-12 versus 1+/-1%, P<0.001) and 30 nM (44+/-12 versus 8+/-3%, P<0.01) 17 beta-oestradiol. FEA was not affected by 100 nM 17 beta-oestradiol. These results demonstrate for the first time that short-term exposure to 17 beta-oestradiol affects FEA in vitro. Human internal mammary arteries have lower FEA than the saphenous veins, but FEA is differentially affected by acute exposure to 17 beta-oestradiol in human arteries and veins. Whether changes in FEA play a role in the vascular effects of 17 beta-oestradiol in vivo remains to be determined.
Medical Policlinic and Clinical Atherosclerosis Research Laboratory, Medical Policlinic, Department of Internal Medicine, University Hospital, Rämistrasse 100, CH-8091 Zürich, Switzerland.
Andres
A
Heigl
Mario
M
Lachat
Thomas
T
Lattmann
Thomas
T
Lüscher
Matthias
M
Barton
D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008323:Mammary Arteries; D008666:Metalloendopeptidases; D011498:Protein Precursors; D012501:Saphenous Vein
D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D004958:Estradiol; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes