Role of copper ions and cytochrome P450 in the vasodilator actions of the nitroxyl anion generator, Angeli's salt, on rat aorta.
Since copper ions catalyse the oxidation of nitroxyl anion to nitric oxide, we investigated whether this might explain the vasodilator actions of the nitroxyl generator, Angeli's salt, in rat aorta. Parallel studies were conducted with S-nitroso-N-acetyl-D,L-penicillamine (SNAP), since Cu ions catalyse the liberation of nitric oxide from this compound. Copper sulphate enhanced relaxation to Angeli's salt and SNAP but this resulted from reduced destruction of nitric oxide by superoxide rather than from enhanced generation of nitric oxide, since it was mimicked by superoxide dismutase and by the superoxide dismutase mimetic, MnCl2. Results with the selective Cu2+ chelators, neocuproine and bathocuproine disulfonate, and the Cu2+ chelators, EDTA, cuprizone and diethyldithiocarbamate, confirmed an important role for endogenous copper in mediating relaxation to SNAP but suggested only a minor role for Angeli's salt. Relaxation to Angeli's salt was, however, powerfully blocked by proadifen, suggesting an important role for cytochrome P450.
Nelli
S
S
Division of Neuroscience and Biomedical Systems, Institute of Biomedical and Life Sciences, West Medical Building, University of Glasgow, G12 8QQ, Scotland, Glasgow, UK.
McIntosh
L
L
Martin
W
W
D000818:Animals; D001011:Aorta / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D019327:Copper Sulfate / Q000378:metabolism*; D003471:Cuprizone / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D017895:Manganese Compounds / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009573:Nitrites / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D010618:Phenanthrolines / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D026423:S-Nitroso-N-Acetylpenicillamine; D019810:Sodium Azide / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D002614:Chelating Agents; D002712:Chlorides; D016166:Free Radical Scavengers; D017895:Manganese Compounds; D020030:Nitric Oxide Donors; D009573:Nitrites; D010618:Phenanthrolines; C021229:oxyhyponitrite; D004958:Estradiol; D003471:Cuprizone; C073106:3,17-diacetoxyestra-1,3,5(10)-trien-2-carboxylic acid; D026423:S-Nitroso-N-Acetylpenicillamine; C002701:neocuproine; D003577:Cytochrome P-450 Enzyme System; D019810:Sodium Azide; D004492:Edetic Acid; C002478:bathocuproine; D011335:Proadifen; D013482:Superoxide Dismutase; D010396:Penicillamine; D019327:Copper Sulfate; C025340:manganese chloride