Endothelium-dependent responses in human isolated thyroid arteries from donors.
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.
Torondel
Belén
B
Department of Physiology, University of Valencia, 46010 Valencia, Spain.
Vila
José M
JM
Segarra
Gloria
G
Lluch
Paloma
P
Medina
Pascual
P
Martínez-León
Juan
J
Ortega
Joaquin
J
Lluch
Salvador
S
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
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