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Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals

Kleinbongard, Petra, Dejam, André, Lauer, Thomas, Rassaf, Tienush, Schindler, Achim, Picker, Olaf, Scheeren, Thomas, Gödecke, Axel, Schrader, Jürgen, Schulz, Rainer, Heusch, Gerd, Schaub, Günter A., Bryan, Nathan S., Feelisch, Martin and Kelm, Malte (2003) Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals Free Radical Biology & Medicine, 35, (7), pp. 790-796. (doi:10.1016/S0891-5849(03)00406-4). (PMID:14583343).

Record type: Article


Changes in plasma nitrite concentration in the human forearm circulation have recently been shown to reflect acute changes in endothelial nitric oxide synthase (eNOS)-activity. Whether basal plasma nitrite is a general marker of constitutive NOS-activity in vivo is yet unclear. Due to the rapid metabolism of nitrite in blood and the difficulties in its analytical determination literature data on levels of nitrite in mammals are largely inconsistent. We hypothesized that constitutive NOS-activity in the circulatory system is relatively uniform throughout the mammalian kingdom. If true, this should result in comparable systemic plasma nitrite levels in different species. Using three different analytical approaches we determined plasma nitrite concentration to be in a nanomolar range in a variety of species: humans (305 +/- 23 nmol/l), monkeys (367 +/- 62 nmol/l), minipigs (319 +/- 24 nmol/l), dogs (305 +/- 50 nmol/l), rabbits (502 +/- 21 nmol/l), guinea pigs (412 +/- 44 nmol/l), rats (191 +/- 43 nmol/l), and mice (457 +/- 51 nmol/l). Application of different NOS-inhibitors in humans, minipigs, and dogs decreased NOS-activity and thereby increased vascular resistance. This was accompanied by a significant, up to 80%, decrease in plasma nitrite concentration. A comparison of plasma nitrite concentrations between eNOS(-/-) and NOS-inhibited wild-type mice revealed that 70 +/- 5% of plasma nitrite is derived from eNOS. These results provide evidence for a uniform constitutive vascular NOS-activity across mammalian species.

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Published date: 1 October 2003
Keywords: nitrite, nitrate, constitutive NOS-activity, vascular resistance, mammals, circulation, free radicals
Organisations: Clinical & Experimental Sciences


Local EPrints ID: 337851
ISSN: 0891-5849
PURE UUID: f332f164-79fb-424e-8959-ec2926ac8821
ORCID for Martin Feelisch: ORCID iD

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Date deposited: 22 Jun 2012 09:54
Last modified: 18 Jul 2017 06:00

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Author: Petra Kleinbongard
Author: André Dejam
Author: Thomas Lauer
Author: Tienush Rassaf
Author: Achim Schindler
Author: Olaf Picker
Author: Thomas Scheeren
Author: Axel Gödecke
Author: Jürgen Schrader
Author: Rainer Schulz
Author: Gerd Heusch
Author: Günter A. Schaub
Author: Nathan S. Bryan
Author: Martin Feelisch ORCID iD
Author: Malte Kelm

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