Fluoride produces endothelium-dependent relaxation and endothelium-independent contraction in coronary artery.
NaF produced endothelium-dependent relaxation and endothelium-independent contraction in porcine, bovine, canine and human coronary artery rings precontracted with either KCl or prostaglandin F2 alpha. For practical reasons the porcine coronary artery was selected to investigate the mechanisms responsible for these responses. Methylene blue, indomethacin, N-ethylmaleimide, pertussis toxin and cholera toxin all significantly attenuated the endothelium-dependent relaxation caused by fluoride. Pretreatment with deferoxamine had no effect on relaxation and superoxide dismutase/catalase potentiated the relaxation produced by fluoride. Fluoride also contracted vessels with or without the endothelium to equal tension levels and had no apparent relaxing effect on basal tone. The contraction produced by fluoride was significantly attenuated by pertussis toxin and cholera toxin; however, none of the other agents examined significantly altered contraction. Bradykinin also caused endothelium-dependent relaxation and this response was significantly attenuated by methylene blue but not indomethacin. Therefore, fluoride appears to relax the arteries by releasing an endothelium-derived relaxing factor similar to that released by bradykinin (methylene blue sensitive) and one or more prostanoid type endothelium-derived relaxing factor(s) (indomethacin sensitive). Furthermore, fluoride relaxation and contraction may be guanine nucleotide-binding regulatory protein-mediated based on sensitivity to the guanine nucleotide-binding regulatory protein modulators.
Cushing
D J
DJ
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina.
Sabouni
M H
MH
Brown
G L
GL
Mustafa
S J
SJ
D000818:Animals; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008751:Methylene Blue / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D012969:Sodium Fluoride / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D009569:Nitric Oxide; D012969:Sodium Fluoride; D013482:Superoxide Dismutase; D019204:GTP-Binding Proteins; D008751:Methylene Blue; D007213:Indomethacin