title: Characterization of big endothelin-1-induced contraction in rabbit saphenous artery.
abstract: We have characterized the endothelin-converting enzyme (ECE)-like activity involved in big endothelin (ET)-1-induced contraction in rabbit saphenous artery (RSA). Big ET-1 30 nM caused a contraction that was independent of the vascular endothelium. Phosphoramidon and the neutral endopeptidase (NEP) inhibitors thiorphan and candoxatrilat blocked the vasoconstriction caused by big ET-1 in endothelium-denuded RSA. Candoxatrilat (IC50 17 nM) and thiorphan (IC50 2.5 nM), were 5- to 30-fold more potent than phosphoramidon (IC50 83 nM). Other protease inhibitors were inactive. In cultured endothelial cells the ET-1 release was inhibited only by phosphoramidon (IC50 16 microM) but at a concentration 200-fold that required an endothelium-denuded RSA. In conclusion, we can speculate that the big ET-1 contraction in RSA is mediated by an ECE, probably present on smooth muscle cells, which is susceptible to NEP inhibitors and is different from the ECE on endothelial cells.
authors.affiliation: Research and Development Division, Zambon Group, Bresso Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Ferlenga
authors.forename: G
authors.initials: G
authors.lastname: Morazzoni
authors.forename: B
authors.initials: B
authors.lastname: Da Ros
authors.forename: E
authors.initials: E
authors.lastname: Branca
authors.forename: M
authors.initials: M
authors.lastname: Fantoni
authors.forename: F
authors.initials: F
authors.lastname: Marchini
authors.forename: F
authors.initials: F
authors.lastname: Pocchiari
authors.forename: C
authors.initials: C
authors.lastname: Semeraro
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D019332:Endothelin-1; D016232:Endothelins / Q000378:metabolism / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011480:Protease Inhibitors / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology*; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D019332:Endothelin-1; D016232:Endothelins; D011480:Protease Inhibitors; D011498:Protein Precursors