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

  • Plane F
  • Wigmore S
  • Angelini G
 et al. 
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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 microM inhibited sodium nitroprusside (SNP; 0.005-10 microM)-evoked relaxation of rat isolated aortic rings precontracted with 3 microM phenylephrine (PE). A lower concentration of DEDCA (10 microM) did not significantly attenuate SNP-evoked responses but did inhibit relaxation to the endothelium-dependent dilator, A23187 (0.01-10 microM). 3. The presence of 100 microM Cu2+, but not 100 microM 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 mu 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 microM and 50 microM, respectively. 7. These data demonstrate that Cu2+ plays a role in controlling NOS and GC activity in the rat aorta.

Author-supplied keywords

  • Animals
  • Aorta
  • Aorta: drug effects
  • Calcimycin
  • Calcimycin: pharmacology
  • Copper
  • Copper: pharmacology
  • Dose-Response Relationship, Drug
  • Guanylate Cyclase
  • Guanylate Cyclase: drug effects
  • Male
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase: drug effects
  • Rats
  • Rats, Inbred WKY

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  • F Plane

  • S Wigmore

  • G D Angelini

  • J Y Jeremy

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