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Diminished L-arginine bioavailability in hypertension.
Clin Sci (Lond). 2004 Oct; 107(4):391-7.CS

Abstract

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 micromol/l) compared with control subjects (137+/-8 micromol/l). L-Arginine transport via system y+L, but not y+, was significantly reduced in RBCs from hypertensive patients (60+/-7 micromol.l(-1).cells(-1).h(-1); n=16) compared with controls (90+/-17 micromol.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.10(9) cells(-1).min(-1) in controls compared with 36+/-9 pmol.10(9) 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/10(8) cells; n=8) compared with controls (0.22+/-0.01 pmol/10(8) 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.

Authors+Show Affiliations

Laboratório de Transporte de Membrana, Departamento de Farmacologia e Psicobiologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20550-20030, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15182236

Citation

Moss, Monique B., et al. "Diminished L-arginine Bioavailability in Hypertension." Clinical Science (London, England : 1979), vol. 107, no. 4, 2004, pp. 391-7.
Moss MB, Brunini TM, Soares De Moura R, et al. Diminished L-arginine bioavailability in hypertension. Clin Sci (Lond). 2004;107(4):391-7.
Moss, M. B., Brunini, T. M., Soares De Moura, R., Novaes Malagris, L. E., Roberts, N. B., Ellory, J. C., Mann, G. E., & Mendes Ribeiro, A. C. (2004). Diminished L-arginine bioavailability in hypertension. Clinical Science (London, England : 1979), 107(4), 391-7.
Moss MB, et al. Diminished L-arginine Bioavailability in Hypertension. Clin Sci (Lond). 2004;107(4):391-7. PubMed PMID: 15182236.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diminished L-arginine bioavailability in hypertension. AU - Moss,Monique B, AU - Brunini,Tatiana M C, AU - Soares De Moura,Roberto, AU - Novaes Malagris,Lúcia E, AU - Roberts,Norman B, AU - Ellory,J Clive, AU - Mann,Giovanni E, AU - Mendes Ribeiro,Antônio C, PY - 2004/06/07/accepted PY - 2004/05/25/revised PY - 2003/12/16/received PY - 2004/6/9/pubmed PY - 2004/11/13/medline PY - 2004/6/9/entrez SP - 391 EP - 7 JF - Clinical science (London, England : 1979) JO - Clin Sci (Lond) VL - 107 IS - 4 N2 - 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 micromol/l) compared with control subjects (137+/-8 micromol/l). L-Arginine transport via system y+L, but not y+, was significantly reduced in RBCs from hypertensive patients (60+/-7 micromol.l(-1).cells(-1).h(-1); n=16) compared with controls (90+/-17 micromol.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.10(9) cells(-1).min(-1) in controls compared with 36+/-9 pmol.10(9) 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/10(8) cells; n=8) compared with controls (0.22+/-0.01 pmol/10(8) 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. SN - 0143-5221 UR - https://www.unboundmedicine.com/medline/citation/15182236/Diminished_L_arginine_bioavailability_in_hypertension_ DB - PRIME DP - Unbound Medicine ER -