Neocuproine, a selective Cu(I) chelator, and the relaxation of rat vascular smooth muscle by S‐nitrosothiols

Abstract

1 A study has been made of the eect of neocuproine, a speci®c Cu(I) chelator, on vasodilator responses of rat isolated perfused tail artery to two nitrosothiols: S-nitroso-N-acetyl-D,L-penicillamine (SNAP) and S-nitroso-glutathione (GSNO). 2 Bolus injections (10 ml) of SNAP or GSNO (10 77 ± 10 73 M) were delivered into the lumen of perfused vessels pre-contracted with sucient phenylephrine (1 ± 7 mM) to develop pressures of 100 ± 120 mmHg. Two kinds of experiment were made: SNAP and GSNO were either (a) pre-mixed with neocuproine (10 74 M) and then injected into arteries; or (b) vessels were continuously perfused with neocuproine (10 75 M) and then injected with either pure SNAP or GSNO. 3 In each case, neocuproine signi®cantly attenuated vasodilator responses to both nitrosothiols, although the nature of the inhibitory eect diered in the two types of experiment. We conclude that the ability of exogenous nitrosothiols to relax vascular smooth muscle in our ex vivo model is dependent upon a Cu(I) catalyzed process. Evidence is presented which suggests that a similar Cu(I)-dependent mechanism is responsible for the release of NO from endogenous nitrosothiols and that this process may assist in maintaining vasodilator tone in vivo.

Detection of S-nitrosothiols in biological fluids: A comparison among the most widely applied methodologies

“…On the other hand, some copper-containing cell-surface proteins, such as ceruloplasmin, would be able to decompose RSNOs, enhancing their NO-mimetic activity (Fig. 2) [23,24]. Thiols can also have an important role in RSNO metabolism since they are ubiquitous and reach millimolar concentrations in the intracellular environment [17].…”

Cooperative Effects in Copper Polyamido­amine Dendrimer Complexes Catalyzing the Reduction of Molecular Oxygen

“…Neocuproine is a Cu I -ionspecific ligand. [26] The resulting complexes exhibited an absorbance maximum at λ = 450 nm. The absorbance at λ Figure 3.…”

“…The concentration of the neocuproine-copper complex was determined by the Beer law (ε = 8000 m -1 cm -1 ). [26] Kojic Acid Titration: The concentrations of 2a, 2b, 2c, 2d, and 2e were 3.3, 3.3, 1.1, 0.44, and 0.33 μm in the Tris buffer, respectively. To the resulting solutions of 2 was added CuSO 4 solution (12, 12, 36, 90, and 120 equiv.…”

Detoxifying Polyhalogenated Catechols through a Copper‐Chelating Agent by Forming Stable and Redox‐Inactive Hydrogen‐Bonded Complexes with an Unusual Perpendicular Structure

“…[3,4] Reductions in toxicity and decreased molecular damage, which are caused by addition of these chelators, have been used to support the involvement of copper in deleterious reactions in vivo and in vitro. [5][6][7][8][9][10][11][12][13] In one of these studies, 2,9-Me 2 OP protected isolated rat hearts against ischemia/reperfusion-induced injury. [13] In another study, BCS reversed copper-mediated growth inhibition of L1210 cells.…”