title: Mechanisms involved in the effects of endothelin-1 in pig prostatic small arteries.
abstract: Since endothelin-1 (ET-1) is involved in prostatic disorders, the current study investigated the mechanisms underlying the ET-1-induced effects in pig prostatic small arteries. The experiments were performed in rings mounted in microvascular myographs containing physiological saline solution at 37oC for isometric force recordings. On basal tension, ET-1 (0.1-30 nM) evoked concentration-dependent contractions, which were enhanced by endothelium removal. ET-1 contractions were inhibited by blockade of endothelin ETA and ETB receptors, extracellular Ca2+ removal and blockade of voltage-dependent (L-type)- and non-voltage-dependent-Ca2+ channels. On endothelium intact rings precontracted with noradrenaline, the ETB endothelin receptor agonist BQ3020 promoted a concentration-dependent relaxation which was reduced by blockade of ETB receptors, nitric oxide synthase, guanylyl cyclase and prostanoids synthesis. Endothelium removal abolished its relaxant response and unmasked a BQ3020-induced contraction. Tetraethylammonium and 4-aminopyridine, blockers of non-selective K+ channels and voltage-dependent K+ (Kv) channels, respectively, inhibited the relaxations to BQ3020. Iberiotoxin, apamin and glibenclamide, blockers of large and small Ca2+-activated- and ATP-dependent- K+ channels, respectively, failed to modify these responses. These data suggest that ET-1 promotes contraction of pig prostatic small arteries by activating vascular smooth muscle contractile endothelin ETA and ETB receptors coupled to extracellular Ca2+ entry, via voltage-dependent (L-type)- and non-voltage-dependent Ca2+ channels, also being due to intracellular Ca2+ mobilization. In addition, a population of endothelial ETB receptors mediates vasorelaxation via NO-cGMP pathway, vasodilator cyclooxygenase product(s) and Kv channels.
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, and Departamento de Investigación, Hospital Universitario Ramón y Cajal 28040-Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Sánchez
authors.forename: Paz
authors.initials: P
authors.lastname: Recio
authors.forename: Luis M
authors.initials: LM
authors.lastname: Orensanz
authors.forename: Salvador
authors.initials: S
authors.lastname: Bustamante
authors.forename: Jorge
authors.initials: J
authors.lastname: Navarro-Dorado
authors.forename: Belén
authors.initials: B
authors.lastname: Climent
authors.forename: Sara
authors.initials: S
authors.lastname: Benedito
authors.forename: Albino
authors.initials: A
authors.lastname: García-Sacristán
authors.forename: Dolores
authors.initials: D
authors.lastname: Prieto
authors.forename: Medardo
authors.initials: M
authors.lastname: Hernández
mesh_terms: D000818:Animals; D001158:Arteries / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D016232:Endothelins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis; D011467:Prostate / Q000098:blood supply*; D017466:Receptors, Endothelin / Q000819:agonists; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D026902:Potassium Channel Blockers; D011453:Prostaglandins; D017466:Receptors, Endothelin; C075771:BQ 3020; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D002118:Calcium