NEOCUPROINE, A SELECTIVE CU(I) CHELATOR, AND THE RELAXATION OF RAT VASCULAR SMOOTH-MUSCLE BY S-NITROSOTHIOLS

1 A study has been made of the effect of neocuproine, a specific Cu(I) chelator, on vasodilator responses of rat isolated perfused tail arte ry to two nitrosothiols: S-nitroso-N-acetyl-D,L-penicillamine (SNAP) a nd S-nitroso-glutathione (GSNO). 2 Bolus injections (10 mu l) of SNAP or GSNO (10(-7)-10(-3) M) Were delivered into the lumen of perfused ve ssels pre-contracted with sufficient phenylephrine (1-7 mu M) to devel op pressures of 100-120 mmHg. Two kinds of experiment were made: SNAP and GSNO were either (a) pre-mixed with neocuproine (10(-4) M) and the n injected into arteries; or (b) vessels were continuously perfused wi th neocuproine (10(-5) M) and then injected with either pure SNAP or G SNO. 3 In each case, neocuproine significantly attenuated vasodilator responses to both nitrosothiols, although the nature of the inhibitory effect differed 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. Evidenc e is presented which suggests that a similar Cu(I)-dependent mechanism is responsible for the release of NO from endogenous nitrosothiols an d that this process may assist in maintaining vasodilator tone in vivo .