Effect of copper on nitric oxide synthase and guanylyl cyclase activity in the rat isolated aorta

Abstract

1 The potential role of copper (Cu 2+ ) in modulating the activity of nitric oxide synthase (NOS) and guanylyl cyclase (GC) was investigated by use of diethyldithiocarbamic acid (DEDCA), a high a nity Cu 2+ chelator. 2 DEDCA 100 mM inhibited sodium nitroprusside (SNP; 0.005 ± 10 mM)-evoked relaxation of rat isolated aortic rings precontracted with 3 mM phenylephrine (PE). A lower concentration of DEDCA (10 mM) did not signi®cantly attenuate SNP-evoked responses but did inhibit relaxation to the endothelium-dependent dilator, A23187 (0.01 ± 10 mM). 3 The presence of 100 mM Cu 2+ , but not 100 mM Fe 2+ , alone enhanced A23187-and SNP-evoked relaxation of aortae precontracted with PE. 4 The inhibitory e ect of DEDCA on SNP-and A23187-induced relaxation was reversed by equimolar concentrations of Cu 2+ but not Fe 2+ , indicating that DEDCA does not act via removal of haem-iron from the NOS and GC complexes. 5 Superoxide dismutase (30 m ml 71 ) was without e ect on the inhibition of DEDCA relaxation induced by either SNP or A23187 in aortae precontracted with PE. 6 When assessed by radioimmunoassay, DEDCA inhibited SNP-and A23187-stimulated cyclic GMP formation with IC 50 values of 0.5 mM and 50 mM, respectively. 7 These data demonstrate that Cu 2+ plays a role in controlling NOS and GC activity in the rat aorta.

Copper Induces Vasorelaxation and Antagonizes Noradrenaline -Induced Vasoconstriction in Rat Mesenteric Artery

“…1A), which was consistent with the previous reports [8,10]. However, in the presence of L-NAME, copper pretreatment still antagonized NA-induced vasoconstriction.…”

“…Indeed, many studies reported that NO was generated markedly in sepsis animal models and septic patients [22,23,24]. Based on that copper stimulated NO production [8,9,10], it was reasonable to speculate that copper might be involved in the vascular hyporeactivity in sepsis through enhancing NO action. However, DTC injection (iv) could not reverse the copper-induced hypotension and could not prevent vascular hyporeactivity to norepinephrine in copper-treated rabbits.…”

“…Copper plays a role in controlling nitric oxide synthase (NOS) and guanylyl cyclase (GC) activity in vessels [8,9]. In rat extrapulmonary artery, copper induced endothelium- and concentration-dependent relaxation through potentiating the action of NO [10].…”

Inhibition of Endothelial Nitric-oxide Synthase by Ceruloplasmin

“…On the contrary, an ability of copper ions (Cu 2ϩ ) to relax vessels seems well established. It has been shown that copper enhances the relaxation of precontracted aortic rings evoked by the calcium ionophore A23187 and sodium nitroprusside (30), and it also elevates intracellular cGMP levels and induces relaxation of pulmonary arterial rings (31). More recently, it has been demonstrated that copper induces the activation of eNOS in cultured endothelial cells (32), an event supposed to occur in vivo in hypercupremic states induced by Cu 2ϩ released by ceruloplasmin.…”

Energy Metabolism of the Brain and Metal-Ligand Homeostasis in the Etiopathogenesis of Ischemic Stroke

“…Такие МИКРОЭЛЕМЕНТЫ В МЕДИЦИНЕ: ОРИГИНАЛЬНЫЕ СТАТЬИ микроэлементы, как селен, хром, цинк, марганец, медь и другие сами являются антиоксидантами ( Zangieva et al, 2013). Медь является кофактором антиоксидантого фермента супероксиддисмутазы: Сu-Zn CОД (Plane et al, 1997;Tsimikas et al, 2012;Azizova et al, 2013;Baskin et al, 2014;Eom et al, 2014). Итак, микроэлементы являются компонентом нейротрофической системы мозга и наравне с це-ребральным энергообменом могут служить марке-рами сохранности мозговой ткани и задолго до клинического проявления сигнализировать об уси-лении патологического процесса в работе ЦНС.…”