The University of Southampton
University of Southampton Institutional Repository

Molecular mechanisms of nitrovasodilator bioactivation

Noack, E. and Feelisch, Martin (1991) Molecular mechanisms of nitrovasodilator bioactivation Basic Research in Cardiology, 86, supplement 2, pp. 37-50. (PMID:1683227).

Record type: Article

Abstract

All nitrovasodilators act intracellularly by a common molecular mechanism. This is characterized by the release of nitric oxide (NO). They are, thus, prodrugs or carriers of the active principle NO, responsible for endothelial controlled vasodilation. The rate of NO-formation strongly correlates with the activation of the soluble guanylate cyclase in vitro, resulting in a stimulation of cGMP synthesis. Nitrovasodilators thus are therapeutic substitutes for endogenous EDRF/NO. The pathways of bioactivation, nevertheless, differ substantially, depending on the individual chemistry of the nitrovasodilator. Besides NO, numerous other reaction products such as nitrite and nitrate anions are formed. The guanylate cyclase is only activated if NO is liberated. In the case of organic nitrates such as GTN, NO is only formed if certain thiol compounds are present as an essential cofactor. The rate of NO-formation correlates with the number of nitrate ester groups and proceeds with a simultaneous nitrite formation (with a ratio of 1:14 in the presence of cysteine). Nitrosamines such as molsidomine do not need thiol compounds for bioactivation. They directly liberate NO from the ring-open A-forms. This process basically depends on the presence of oxygen as electron acceptor from the sydnonimine molecule. Therefore, besides NO also superoxide radicals are formed, which may react with the generated NO under formation of nitrate ions. Organic nitrites (such as amyl nitrite) require the preceding interaction with a mercapto group to form a S-nitrosothiol intermediate, from which finally NO radicals are liberated. Nitrosothiols (like S-nitroso-acetyl-penicillamine) and sodium nitroprusside spontaneously release NO. The molecules themselves do not possess a direct enzyme activating potency. In the presence of thiol compounds organic nitrites (e.g., amyl nitrite) and nitrosothiols may act as intermediary products of NO generation.

Full text not available from this repository.

More information

Published date: 1991
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 337917
URI: http://eprints.soton.ac.uk/id/eprint/337917
ISSN: 0300-8428
PURE UUID: e15ee35d-ef19-4d63-9922-f7b3c5e94792
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

Catalogue record

Date deposited: 29 May 2012 11:37
Last modified: 18 Jul 2017 06:00

Export record

Contributors

Author: E. Noack
Author: Martin Feelisch ORCID iD

University divisions

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.

×