Accumulation of the endogenous L-arginine analogue NG-monomethyl-L-arginine in human end-stage renal failure patients on regular haemodialysis.
We measured plasma levels of L-arginine, its analogue NG-monomethyl-L-arginine (L-NMMA), and related amino acids in normal subjects and uraemic patients (n = 31), before and after haemodialysis. Plasma levels of L-arginine were reduced to less than half of normal values in uraemic subjects compared with controls, and were not affected by haemodialysis. L-NMMA was not detectable in non-uraemic subjects, but markedly elevated in uraemic patients. In parallel, we used human red blood cells as a model to study the effect of L-NMMA upon the transport of L-arginine. L-NMMA trans-stimulated L-arginine transport significantly, confirming that L-arginine and L-NMMA share common transport pathways. Our results suggest altered L-arginine metabolism and the presence of an increased concentration of a NO synthase inhibitor in uraemia. We propose that alterations in plasma L-arginine levels and increased production of L-arginine analogues will alter NO synthesis and may help to explain some pathological changes seen in uraemia.
Mendes Ribeiro
A C
AC
University Laboratory of Physiology, Oxford, UK.
Roberts
N B
NB
Lane
C
C
Yaqoob
M
M
Ellory
J C
JC
D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D001692:Biological Transport; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000097:blood; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood*; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D006435:Renal Dialysis; D012588:Scintillation Counting; D014511:Uremia / Q000097:blood; D019323:omega-N-Methylarginine
D001120:Arginine; D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; C092506:N(G)-monomethylarginine acetate; D019323:omega-N-Methylarginine; C018524:N,N-dimethylarginine