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

Abstract

1. The potential role of copper (Cu²⁺) in modulating the activity of nitric oxide synthase (NOS) and guanylyl cyclase (GC) was investigated by use of diethyldithiocarbamic acid (DEDCA), a high affinity Cu²⁺ chelator.

2. DEDCA 100 μM inhibited sodium nitroprusside (SNP; 0.005–10 μM)-evoked relaxation of rat isolated aortic rings precontracted with 3 μM phenylephrine (PE). A lower concentration of DEDCA (10 μM) did not significantly attenuate SNP-evoked responses but did inhibit relaxation to the endothelium-dependent dilator, A23187 (0.01–10 μM).

3. The presence of 100 μM Cu²⁺, but not 100 μM Fe²⁺, alone enhanced A23187- and SNP-evoked relaxation of aortae precontracted with PE.

4. The inhibitory effect of DEDCA on SNP- and A23187-induced relaxation was reversed by equimolar concentrations of Cu²⁺ but not Fe²⁺, indicating that DEDCA does not act via removal of haem-iron from the NOS and GC complexes.

5. Superoxide dismutase (30 μ ml⁻¹) was without effect 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 IC₅₀ values of 0.5 μM and 50 μM, respectively.

7. These data demonstrate that Cu²⁺ plays a role in controlling NOS and GC activity in the rat aorta.

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