The University of Southampton
University of Southampton Institutional Repository

Oxidative release of nitric oxide accounts for guanylyl cyclase stimulating, vasodilator and anti-platelet activity of Piloty's acid: a comparison with Angeli's salt

Oxidative release of nitric oxide accounts for guanylyl cyclase stimulating, vasodilator and anti-platelet activity of Piloty's acid: a comparison with Angeli's salt
Oxidative release of nitric oxide accounts for guanylyl cyclase stimulating, vasodilator and anti-platelet activity of Piloty's acid: a comparison with Angeli's salt
The decomposition of benzenesulphohydroxamic acid (Piloty's acid; PA) and some of its derivatives has been reported to yield nitroxyl ions (NO-), a species with potent vasodilator properties. In a previous study we demonstrated that the oxidative breakdown of PA results in the formation of nitric oxide (NO) and suggested that NO rather than NO- may account for its vasorelaxant properties. Using isolated aortic rings in organ baths, we now show that high concentrations of cysteine potentiate the vasorelaxant response to PA, whereas responses to Angeli's salt (AS), a known generator of NO-, were almost completely inhibited. These different behaviours of PA and AS are mirrored by their distinct chemistries. By using HPLC it was shown that, at physiological pH and in the absence of oxidizing conditions, PA is a relatively stable compound. Direct chemical determination of NO, stimulation of soluble guanylyl cyclase, and measurement of platelet aggregation under various experimental conditions confirmed the requirement for oxidation to release NO from PA, and quite weak oxidants were found to be sufficient to promote this reaction. In contrast, at pH 7.4 AS decomposed rapidly to yield nitrite (NO2-) and NO-, bu did not produce NO on reaction with dioxygen (O2) or hydrogen peroxide (H2O2). Thus sulphohydroxamic acids are a new class of thiol-independent NO-donors that generate NO rather than NO- under physiological conditions.
1470-8728
333-339
Zamora, R.
6115e138-414f-4403-8973-129f3ef1d2fb
Grzesiok, A.
50acdca2-7eea-4262-a26c-881f5fc2e2fd
Weber, H.
c4b82e7b-7b62-47fa-b016-a143dca94f01
Feelisch, M.
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Zamora, R.
6115e138-414f-4403-8973-129f3ef1d2fb
Grzesiok, A.
50acdca2-7eea-4262-a26c-881f5fc2e2fd
Weber, H.
c4b82e7b-7b62-47fa-b016-a143dca94f01
Feelisch, M.
8c1b9965-8614-4e85-b2c6-458a2e17eafd

Zamora, R., Grzesiok, A., Weber, H. and Feelisch, M. (1995) Oxidative release of nitric oxide accounts for guanylyl cyclase stimulating, vasodilator and anti-platelet activity of Piloty's acid: a comparison with Angeli's salt. Biochemical Journal, 312 (Pt 2), 333-339. (PMID:8526840)

Record type: Article

Abstract

The decomposition of benzenesulphohydroxamic acid (Piloty's acid; PA) and some of its derivatives has been reported to yield nitroxyl ions (NO-), a species with potent vasodilator properties. In a previous study we demonstrated that the oxidative breakdown of PA results in the formation of nitric oxide (NO) and suggested that NO rather than NO- may account for its vasorelaxant properties. Using isolated aortic rings in organ baths, we now show that high concentrations of cysteine potentiate the vasorelaxant response to PA, whereas responses to Angeli's salt (AS), a known generator of NO-, were almost completely inhibited. These different behaviours of PA and AS are mirrored by their distinct chemistries. By using HPLC it was shown that, at physiological pH and in the absence of oxidizing conditions, PA is a relatively stable compound. Direct chemical determination of NO, stimulation of soluble guanylyl cyclase, and measurement of platelet aggregation under various experimental conditions confirmed the requirement for oxidation to release NO from PA, and quite weak oxidants were found to be sufficient to promote this reaction. In contrast, at pH 7.4 AS decomposed rapidly to yield nitrite (NO2-) and NO-, bu did not produce NO on reaction with dioxygen (O2) or hydrogen peroxide (H2O2). Thus sulphohydroxamic acids are a new class of thiol-independent NO-donors that generate NO rather than NO- under physiological conditions.

Other
1995 Zamora-Biochem J.PDF - Other
Download (871kB)

More information

Published date: 1 December 1995
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 337896
URI: http://eprints.soton.ac.uk/id/eprint/337896
ISSN: 1470-8728
PURE UUID: 47332ea2-9985-49de-a380-8764d6096083
ORCID for M. Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

Catalogue record

Date deposited: 29 Jun 2012 14:30
Last modified: 15 Mar 2024 03:41

Export record

Contributors

Author: R. Zamora
Author: A. Grzesiok
Author: H. Weber
Author: M. Feelisch ORCID iD

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×