UNDERSTANDING THE CONTROVERSY OVER THE IDENTITY OF EDRF

THIRTEEN years after its discovery(1), there is still controversy over the chemical identity of endothelium-derived relaxing factor (EDRF). Although pharmacological and chemical evidence indicates that EDRF is nitric oxide(2), other candidates, including S-nitrosocysteine(3,4), c omplex(5), nitroxyl(6) and hydroxylamine(7), have been proposed to acc ount for the vasorelaxant properties of EDRF. Such diverse compounds s hould differ in their stability and in reactivity with oxyhaemoglobin and with redox-active nucleophiles such as thiols. Here we use a bioas say to compare the pharmacodynamic profiles of these and other compoun ds with those of nitric oxide and EDRF. We find that some S-nitrosothi ols, dinitrosyl-iron-cysteine complex, sodium nitroxyl and hydroxylami ne can be eliminated as candidates as they are more stable than EDRF a nd less susceptible to inhibition by oxyhaemoglobin. Co-infusion of cy steine revealed major differences between the remaining candidates bec ause it reduced the effect of authentic nitric oxide and EDRF on the b ioassay tissues but enhanced the survival of S-nitrosocysteine and S-n itroso-cysteamine. Our results further support the evidence that EDRF, the pharmacological entity described by Furchgott and Zawadzki(1), is nitric oxide.