The University of Southampton
University of Southampton Institutional Repository

Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action

Lauer, Thomas, Preik, Michael, Rassaf, Tienush, Strauer, Bodo E., Deussen, Andreas, Feelisch, Martin and Kelm, Malte (2001) Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action Proceedings of the National Academy of Sciences, 98, (22), pp. 12814-12819. (doi:10.1073/pnas.221381098). (PMID:11606734).

Record type: Article


The plasma level of NO(x), i.e., the sum of NO(2)- and NO(3)-, is frequently used to assess NO bioavailability in vivo. However, little is known about the kinetics of NO conversion to these metabolites under physiological conditions. Moreover, plasma nitrite recently has been proposed to represent a delivery source for intravascular NO. We therefore sought to investigate in humans whether changes in NO(x) concentration are a reliable marker for endothelial NO production and whether physiological concentrations of nitrite are vasoactive. NO(2)- and NO(3)- concentrations were measured in blood sampled from the antecubital vein and brachial artery of 24 healthy volunteers. No significant arterial-venous gradient was observed for either NO(2)- or NO(3)-. Endothelial NO synthase (eNOS) stimulation with acetylcholine (1-10 microg/min) dose-dependently augmented venous NO(2)- levels by maximally 71%. This effect was paralleled by an almost 4-fold increase in forearm blood flow (FBF), whereas an equieffective dose of papaverine produced no change in venous NO(2)-. Intraarterial infusion of NO(2)- had no effect on FBF. NOS inhibition (N(G)-monomethyl-l-arginine; 4-12 micromol/min) dose-dependently reduced basal NO(2)- and FBF and blunted acetylcholine-induced vasodilation and NO release by more than 80% and 90%, respectively. In contrast, venous NO(3)- and total NO(x) remained unchanged as did systemic arterial NO(2)- and NO(3)- levels during all these interventions. FBF and NO release showed a positive association (r = 0.85; P < 0.001). These results contradict the current paradigm that plasma NO(3)- and/or total NO(x) are generally useful markers of endogenous NO production and demonstrate that only NO(2)- reflects acute changes in regional eNOS activity. Our results further demonstrate that physiological levels of nitrite are vasodilator-inactive.

Full text not available from this repository.

More information

e-pub ahead of print date: 16 October 2001
Published date: 23 October 2001
Keywords: endotheliu, blood flo, red blood cell, endothelial dysfunction
Organisations: Clinical & Experimental Sciences


Local EPrints ID: 337868
ISSN: 0027-8424
PURE UUID: 88961e68-b4a5-410b-baa1-fb973b9bd910
ORCID for Martin Feelisch: ORCID iD

Catalogue record

Date deposited: 22 Jun 2012 13:38
Last modified: 18 Jul 2017 06:00

Export record



Author: Thomas Lauer
Author: Michael Preik
Author: Tienush Rassaf
Author: Bodo E. Strauer
Author: Andreas Deussen
Author: Martin Feelisch ORCID iD
Author: Malte Kelm

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 supports OAI 2.0 with a base URL of

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.