L-Arginine is the precursor of NO (nitric oxide), a key endogenous mediator involved in endothelium-dependent vascular relaxation and platelet function. Although the concentration of intracellular L-arginine is well above the Km for NO synthesis, in many cells and pathological conditions the transport of L-arginine is essential for NO production (L-arginine paradox). The present study was designed to investigate the modulation of L-arginine/NO pathway in systemic arterial hypertension. Transport of L-arginine into RBCs (red blood cells) and platelets, NOS (NO synthase) activity and amino acid profiles in plasma were analysed in hypertensive patients and in an animal model of hypertension. Influx of L-arginine into RBCs was mediated by the cationic amino acid transport systems y+ and y+L, whereas, in platelets, influx was mediated only via system y+L. Chromatographic analyses revealed higher plasma levels of L-arginine in hypertensive patients (175±19 μmol/l) compared with control subjects (137±8 μmol/l). L-Arginine transport via system y+L, but not y+, was significantly reduced in RBCs from hypertensive patients (60±7 μmol·l−1·cells−1·h−1; n=16) compared with controls (90±17 μmol·l−1·cells−1·h−1; n=18). In human platelets, the Vmax for L-arginine transport via system y+L was 86±17 pmol·109 cells−1·min−1 in controls compared with 36±9 pmol·109 cells−1·min−1 in hypertensive patients (n=10; P<0.05). Basal NOS activity was decreased in platelets from hypertensive patients (0.12±0.02 pmol/108 cells; n=8) compared with controls (0.22±0.01 pmol/108 cells; n=8; P<0.05). Studies with spontaneously hypertensive rats demonstrated that transport of L-arginine via system y+L was also inhibited in RBCs. Our findings provide the first evidence that hypertension is associated with an inhibition of L-arginine transport via system y+L in both humans and animals, with reduced availability of L-arginine limiting NO synthesis in blood cells.
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October 2004
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Research Article|
September 24 2004
Diminished L-arginine bioavailability in hypertension
Monique B. MOSS;
Monique B. MOSS
*Laboratório de Transporte de Membrana, Departamento de Farmacologia e Psicobiologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20550-20030, Brazil
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Tatiana M. C. BRUNINI;
Tatiana M. C. BRUNINI
*Laboratório de Transporte de Membrana, Departamento de Farmacologia e Psicobiologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20550-20030, Brazil
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Roberto SOARES de MOURA;
Roberto SOARES de MOURA
*Laboratório de Transporte de Membrana, Departamento de Farmacologia e Psicobiologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20550-20030, Brazil
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Lúcia E. NOVAES MALAGRIS;
Lúcia E. NOVAES MALAGRIS
*Laboratório de Transporte de Membrana, Departamento de Farmacologia e Psicobiologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20550-20030, Brazil
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Norman B. ROBERTS;
Norman B. ROBERTS
†Department of Clinical Chemistry, Royal Liverpool Hospital, Liverpool, L7 8XP, U.K.
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J. Clive ELLORY;
J. Clive ELLORY
‡University Laboratory of Physiology, University of Oxford, Parks Road, Oxford OX1 3PT, U.K.
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Giovanni E. MANN;
Giovanni E. MANN
§Centre for Cardiovascular Biology and Medicine, GKT School of Biomedical Sciences, King's College London, Guy's Campus, London SE1 1UL, U.K.
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Antônio C. MENDES RIBEIRO
*Laboratório de Transporte de Membrana, Departamento de Farmacologia e Psicobiologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20550-20030, Brazil
Correspondence: Dr Antônio Mendes Ribeiro (email [email protected]).
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Publisher: Portland Press Ltd
Received:
December 16 2003
Revision Received:
May 25 2004
Accepted:
June 07 2004
Accepted Manuscript online:
June 07 2004
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society
2004
Clin Sci (Lond) (2004) 107 (4): 391–397.
Article history
Received:
December 16 2003
Revision Received:
May 25 2004
Accepted:
June 07 2004
Accepted Manuscript online:
June 07 2004
Citation
Monique B. MOSS, Tatiana M. C. BRUNINI, Roberto SOARES de MOURA, Lúcia E. NOVAES MALAGRIS, Norman B. ROBERTS, J. Clive ELLORY, Giovanni E. MANN, Antônio C. MENDES RIBEIRO; Diminished L-arginine bioavailability in hypertension. Clin Sci (Lond) 1 October 2004; 107 (4): 391–397. doi: https://doi.org/10.1042/CS20030412
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