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Am J Physiol Heart Circ Physiol 273: H2843-H2849, 1997;
0363-6135/97 $5.00
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Vol. 273, Issue 6, H2843-H2849, December 1997

Ceruloplasmin impairs endothelium-dependent relaxation of rabbit aorta

Maurizio Cappelli-Bigazzi1, Giuseppe Ambrosio2, Giovanni Musci3, Carmine Battaglia1, Maria Carmela Bonaccorsi Di Patti4, Paolo Golino1, Massimo Ragni1, Massimo Chiariello1, and Lilia Calabrese5

1 Division of Cardiology, Second School of Medicine, University of Naples, Naples 80131; 2 Division of Cardiology, School of Medicine, University of Perugia, Perugia 06100; 3 Department of Organic and Biological Chemistry, University of Messina, Messina 98166; 4 Department of Biochemical Sciences and Consiglio Nazionale delle Ricerche Center of Molecular Biology, University of Rome, La Sapienza, Rome 00185; and 5 Department of Biology, University of Rome, Roma Tre, Rome 00154, Italy

This study evaluated the effects of ceruloplasmin, the copper-containing blue oxidase of vertebrate plasma, on the relaxation of rabbit aortic rings after endothelial release of nitric oxide (NO). Ceruloplasmin at physiological, i.e., micromolar, concentrations inhibited relaxation of rabbit aorta induced by endothelium-dependent agonists like acetylcholine or ADP, whereas it was ineffective toward vasodilation due to direct stimulation of smooth muscle cells by nitroglycerin. The effect was reversible and specific for native, fully metalated ceruloplasmin, since relaxation was not impaired by the heat-treated or metal-depleted derivatives. A trapping mechanism, involving a direct interaction of NO or other NO-containing species (like nitrosothiols and iron-dinitrosyls) with the copper sites and/or with the free thiol of ceruloplasmin, could be safely excluded on the basis of spectroscopic and chemical analyses of the protein exposed to authentic NO, nitrosothiols, or iron-dinitrosyls. The data presented in this paper constitute the first evidence of impairment of the endothelium-dependent vasodilatation by a plasma protein and may shed some light on the still uncertain physiological role of ceruloplasmin.

nitric oxide; copper


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