Selective inhibition of endothelium-dependent relaxation by gold-containing compounds.
Gold-containing compounds inhibited endothelium-dependent relaxation mediated by acetylcholine and the calcium ionophore A23187 in isolated rabbit thoracic aortic rings. Auranofin was the most potent gold-containing compound studied, producing approximately 40% inhibition of vascular relaxation at a concentration of 1 microM. Concentration-response curves to vascular relaxation produced by sodium nitroprusside were significantly shifted 5-fold to the left in the presence of auranofin. However, concentration-response curves to vascular relaxation produced by nitric oxide or isoproterenol were unaffected by auranofin. A series of other gold-containing compounds also inhibited endothelium-dependent relaxation with varying degrees of potency, but none approaching that observed with auranofin. These findings reveal that certain gold-containing compounds are potent and selective inhibitors of endothelium-dependent relaxation.
Ohlstein
E H
EH
Department of Pharmacology, Smith Kline & French Laboratories, King of Prussia, Pa.
Horohonich
S
S
D000818:Animals; D001310:Auranofin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects*; D006046:Gold / Q000494:pharmacology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology; D009942:Organometallic Compounds / Q000494:pharmacology*; D011817:Rabbits
D009942:Organometallic Compounds; D009569:Nitric Oxide; D000001:Calcimycin; D001310:Auranofin; D006046:Gold; D007545:Isoproterenol