title: Endothelium-dependent responses in human isolated thyroid arteries from donors.
abstract: The functional properties of the endothelium of human thyroid arteries remain unexplored. We investigated the intervention of nitric oxide (NO), prostacyclin (PGI(2)) and endothelium-derived hyperpolarizing factor (EDHF) in the responses to acetylcholine and noradrenaline in isolated thyroid arteries obtained from multi-organ donors. Artery rings were suspended in organ baths for isometric recording of tension. The contribution of NO, PGI(2) and EDHF to endothelium-dependent relaxation was determined by the inhibitory effects of N(G)-monomethyl-L-arginine (L-NMMA), indomethacin, and K(+) channel inhibitors respectively. Acetylcholine induced concentration-dependent relaxation; this effect was not modified by indomethacin and was only partly reduced by L-NMMA, but was abolished in endothelium-denuded rings. The relaxation resistant to indomethacin and L-NMMA was abolished by using either apamin combined with charybdotoxin, ouabain plus barium, or a high-K(+) solution. Noradrenaline induced concentration-dependent contractions which were of greater magnitude in arteries denuded of endothelium or in the presence of L-NMMA. In conclusion, the results indicate that in human thyroid arteries the endothelium significantly modulates responses to acetylcholine and noradrenaline through the release of NO and EDHF. EDHF plays a dominant role in acetylcholine-induced relaxation through activation of Ca(2+)-activated K(+) channels, inwardly rectifying K(+) channels and Na(+)-K(+)-ATPase.
authors.affiliation: Department of Physiology, University of Valencia, 46010 Valencia, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Torondel
authors.forename: José M
authors.initials: JM
authors.lastname: Vila
authors.forename: Gloria
authors.initials: G
authors.lastname: Segarra
authors.forename: Paloma
authors.initials: P
authors.lastname: Lluch
authors.forename: Pascual
authors.initials: P
authors.lastname: Medina
authors.forename: Juan
authors.initials: J
authors.lastname: Martínez-León
authors.forename: Joaquin
authors.initials: J
authors.lastname: Ortega
authors.forename: Salvador
authors.initials: S
authors.lastname: Lluch
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D001030:Apamin / Q000494:pharmacology; D001158:Arteries / Q000378:metabolism; D001685:Biological Factors / Q000378:metabolism; D018999:Charybdotoxin / Q000494:pharmacology; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000494:pharmacology; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013961:Thyroid Gland / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D001685:Biological Factors; D010455:Peptides; D026902:Potassium Channel Blockers; C067410:endothelium-dependent hyperpolarization factor; D018999:Charybdotoxin; D001030:Apamin; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C064719:iberiotoxin; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D000254:Sodium-Potassium-Exchanging ATPase; D000109:Acetylcholine; D009638:Norepinephrine; D007213:Indomethacin