CERULOPLASMIN IMPAIRS ENDOTHELIUM-DEPENDENT RELAXATION OF RABBIT AORTA

This study evaluated the effects of ceruloplasmin, the copper-containi ng blue oxidase of vertebrate plasma, on the relaxation of rabbit aort ic rings after endothelial release of nitric oxide (NO). Ceruloplasmin at physiological, i.e., micromolar, concentrations inhibited relaxati on of rabbit aorta induced by endothelium-dependent agonists hire acet ylcholine or ADP, whereas it was ineffective toward vasodilation due t o direct stimulation of smooth muscle cells by nitroglycerin. The effe ct was reversible and specific for native, fully metalated ceruloplasm in, since relaxation was not impaired by the heat-treated or metal-dep leted derivatives. A trapping mechanism, involving a direct interactio n of NO or other NO-containing species (like nitrosothiols and iron-di nitrosyls) with the copper sites and/or with the free thiol of cerulop lasmin, could be safely excluded on the basis of spectroscopic and che mical analyses of the protein exposed to authentic NO, nitrosothiols, or iron-dinitrosyls. The data presented in this paper constitute the f irst evidence of impairment of the endothelium-dependent vasodilatatio n by a plasma protein and may shed some Light on the still uncertain p hysiological role of ceruloplasmin.