Abstract.
Bleeding tendency in uraemic patients seems to be related to alterations in the activity of the L-arginine-nitric oxide (NO) signalling pathway in platelets. We have reported previously that L-arginine influx into human platelets is mediated by the high-affinity cationic amino acid transport system y+L. In the present study we examined the dependency of nitric oxide synthase (NOS) activity on L-arginine transport in platelets isolated from healthy controls and uraemic patients on haemodialysis. We investigated basal and ADP-stimulated NOS activity, as reflected by the conversion of L-[3H]arginine to L-[3H]citrulline, in platelets obtained from healthy controls and uraemic patients on haemodialysis. To determine whether NOS activity depended on L-arginine transport, we analysed the effects of competitive inhibitors of L-arginine transport via system y+L on NOS activity. Basal NOS activity was increased from 0.21±0.06 to 0.7±0.2 pmol/108 platelets (n=9, P<0.05) in uraemic patients. Stimulation by ADP (10 µM) significantly increased NOS activity (inhibitable by L-NAME) in control platelets (252%) but failed to increase further the elevated NOS activity in uraemic platelets. Homocysteine and L-leucine, competitive inhibitors of system y+L, markedly inhibited NOS activity in uraemic platelets. These observations indicate that platelets from uraemic patients on haemodialysis generate more NO than control platelets and that entry of L-arginine via system y+L is most likely rate-limiting for platelet NO production in chronic renal failure.
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Brunini, .T., Yaqoob, .M., Novaes Malagris, .L. et al. Increased nitric oxide synthesis in uraemic platelets is dependent on L-arginine transport via system y+L. Pflugers Arch - Eur J Physiol 445, 547–550 (2003). https://doi.org/10.1007/s00424-002-0978-7
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DOI: https://doi.org/10.1007/s00424-002-0978-7