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Understanding the controversy over the identity of EDRF

Understanding the controversy over the identity of EDRF
Understanding the controversy over the identity of EDRF
Thirteen years after its discovery, 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, other candidates, including S-nitrosocysteine, dinitrosyl-iron-cysteine complex, nitroxyl and hydroxylamine, have been proposed to account for the vasorelaxant properties of EDRF. Such diverse compounds should differ in their stability and in reactivity with oxyhaemoglobin and with redox-active nucleophiles such as thiols. Here we use a bioassay to compare the pharmacodynamic profiles of these and other compounds with those of nitric oxide and EDRF. We find that some S-nitrosothiols, dinitrosyl-iron-cysteine complex, sodium nitroxyl and hydroxylamine can be eliminated as candidates as they are more stable than EDRF and less susceptible to inhibition by oxyhaemoglobin. Co-infusion of cysteine revealed major differences between the remaining candidates because it reduced the effect of authentic nitric oxide and EDRF on the bioassay tissues but enhanced the survival of S-nitrosocysteine and S-nitrosocysteamine. Our results further support the evidence that EDRF, the pharmacological entity described by Furchgott and Zawadzki, is nitric oxide.
0028-0836
62-65
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
te Poel, Marc
8f98fb8c-67a1-4c99-b4f5-27bf3e343a17
Zamora, Rubén
f06543b2-2e58-4d2a-b1f4-54f00b2179d8
Deussen, Andreas
cc66975e-8cf4-40fd-a531-bcf52af65dc2
Moncada, Salvador
0f661842-cd67-46e6-b82d-47f2c5e0e750
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
te Poel, Marc
8f98fb8c-67a1-4c99-b4f5-27bf3e343a17
Zamora, Rubén
f06543b2-2e58-4d2a-b1f4-54f00b2179d8
Deussen, Andreas
cc66975e-8cf4-40fd-a531-bcf52af65dc2
Moncada, Salvador
0f661842-cd67-46e6-b82d-47f2c5e0e750

Feelisch, Martin, te Poel, Marc, Zamora, Rubén, Deussen, Andreas and Moncada, Salvador (1994) Understanding the controversy over the identity of EDRF. Nature, 368 (6466), 62-65. (doi:10.1038/368062a0). (PMID:8107883)

Record type: Article

Abstract

Thirteen years after its discovery, 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, other candidates, including S-nitrosocysteine, dinitrosyl-iron-cysteine complex, nitroxyl and hydroxylamine, have been proposed to account for the vasorelaxant properties of EDRF. Such diverse compounds should differ in their stability and in reactivity with oxyhaemoglobin and with redox-active nucleophiles such as thiols. Here we use a bioassay to compare the pharmacodynamic profiles of these and other compounds with those of nitric oxide and EDRF. We find that some S-nitrosothiols, dinitrosyl-iron-cysteine complex, sodium nitroxyl and hydroxylamine can be eliminated as candidates as they are more stable than EDRF and less susceptible to inhibition by oxyhaemoglobin. Co-infusion of cysteine revealed major differences between the remaining candidates because it reduced the effect of authentic nitric oxide and EDRF on the bioassay tissues but enhanced the survival of S-nitrosocysteine and S-nitrosocysteamine. Our results further support the evidence that EDRF, the pharmacological entity described by Furchgott and Zawadzki, is nitric oxide.

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Published date: 3 March 1994
Organisations: Clinical & Experimental Sciences

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Local EPrints ID: 337907
URI: http://eprints.soton.ac.uk/id/eprint/337907
ISSN: 0028-0836
PURE UUID: 317792c4-1eb2-46cd-a15c-a6a8c2c93d5f
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 15 Jun 2012 13:32
Last modified: 15 Mar 2024 03:42

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Author: Martin Feelisch ORCID iD
Author: Marc te Poel
Author: Rubén Zamora
Author: Andreas Deussen
Author: Salvador Moncada

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