Results regarding the nitric oxide (NO) system in uraemia are contradictory. l-Arginine, the precursor of NO, is also metabolized by arginase to form ornithine and urea. In the present study, endothelial NO production and arginine metabolism in uraemia were assessed. In addition an in vivo model was used to examine excess consumption of NO in uraemia. NO and amino acid measurements were made from basal and stimulated (by bradykinin) uraemic and control endothelial cells. Reverse-transcriptase PCR was used to assess endothelial NO synthase (eNOS) and inducible NOS (iNOS) expression. Finally, aortae of uraemic rats were stained for nitrotyrosine (a marker of peroxynitrite). Basal uraemic cells produced more NO than the control cells. l-Arginine levels were greater in uraemic (supernatants/cells), but ornithine levels were higher in control (supernatants/cells). Following stimulation, NO levels in supernatants were similar, but the rise in NO production was greater in control compared with uraemic cells; l-arginine levels still remained higher in uraemic supernatants/cells. Differences in ornithine concentration (supernatants/cells) disappeared following bradykinin stimulation, due to a rise in ornithine levels in the uraemic group. There was no difference in eNOS expression, nor was iNOS detected in either group. Only aortae from uraemic rats showed evidence for nitrotyrosine staining. These studies demonstrated increased basal NO release in uraemic endothelial cells, perhaps by inhibition of arginase and hence diversion of arginine to the NO pathway. The increased NO produced under basal conditions may be inactive due to excessive consumption, resulting in peroxynitrite formation. Interestingly, bradykinin appears to restore arginase activity in uraemia, resulting in normalization of NO production.
Skip Nav Destination
Article navigation
Research Article|
June 06 2002
Altered l-arginine metabolism results in increased nitric oxide release from uraemic endothelial cells
Raj C. THURAISINGHAM;
*Anthony Raine Research Laboratory, St. Bartholomew's Hospital, Queen Mary and Westfield College, London EC1A 7BE, U.K.
Correspondence: Dr R.C. Thuraisingham, Department of Renal Medicine and Transplantation, Royal London Hospital, Whitechapel, London E1 1BB, U.K. (e-mail [email protected]).
Search for other works by this author on:
Norman B. ROBERTS;
Norman B. ROBERTS
†Department of Clinical Chemistry, Royal Liverpool University Hospital, Liverpool L7 8XP, U.K.
Search for other works by this author on:
Mark WILKES;
Mark WILKES
‡Department of Anaesthetics, University Hospital NHS Trust, Queen Elizabeth Hospital, Edgebaston, Birmingham B15 2TH, U.K.
Search for other works by this author on:
David I. NEW;
David I. NEW
*Anthony Raine Research Laboratory, St. Bartholomew's Hospital, Queen Mary and Westfield College, London EC1A 7BE, U.K.
Search for other works by this author on:
A. Claudio MENDES-RIBEIRO;
A. Claudio MENDES-RIBEIRO
*Anthony Raine Research Laboratory, St. Bartholomew's Hospital, Queen Mary and Westfield College, London EC1A 7BE, U.K.
§Departamento de Farmacologia e Psicobiologia, Universidade do Estado do Rio De Janeiro, Av 28 de Setembro 87, Rio de Janeiro, RJ, 20551-030, Brazil
Search for other works by this author on:
Susan M. DODD;
Susan M. DODD
*Anthony Raine Research Laboratory, St. Bartholomew's Hospital, Queen Mary and Westfield College, London EC1A 7BE, U.K.
Search for other works by this author on:
Muhammad M. YAQOOB
Muhammad M. YAQOOB
*Anthony Raine Research Laboratory, St. Bartholomew's Hospital, Queen Mary and Westfield College, London EC1A 7BE, U.K.
Search for other works by this author on:
Publisher: Portland Press Ltd
Accepted:
April 08 2001
Received:
November 28 2001
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2002
2002
Clin Sci (Lond) (2002) 103 (1): 31–41.
Article history
Accepted:
April 08 2001
Received:
November 28 2001
Citation
Raj C. THURAISINGHAM, Norman B. ROBERTS, Mark WILKES, David I. NEW, A. Claudio MENDES-RIBEIRO, Susan M. DODD, Muhammad M. YAQOOB; Altered l-arginine metabolism results in increased nitric oxide release from uraemic endothelial cells. Clin Sci (Lond) 1 July 2002; 103 (1): 31–41. doi: https://doi.org/10.1042/cs1030031
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Cited By
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() |