Dimethylarginines in chronic renal failure.

Abstract

Background--Nitric oxide (NO) is a potent chemical mediator involved in many functions. In vivo production of NO is thought to be regulated by endogenous analogues of L-arginine: asymmetric dimethylarginine (ADMA).

Aim--To examine the effect of renal function and dialysis on the serum concentrations of ADMA and symmetric dimethylarginine (SDMA).

Methods--Blood samples were obtained from nine healthy subjects, patients with renal failure before (n = 17) and after haemodialysis (n = 9), nine patients on chronic ambulatory peritoneal dialysis (CAPD), and 13 patients with chronic renal failure on conservative treatment. Serum samples were extracted using a solid phase cation exchange column and the extracts were analysed by high performance liquid chromatography (HPLC).

Results--Serum concentrations of ADMA in patients with renal failure (mean, 1.04 [micro]mol/litre; SD, 0.17) were significantly higher than those of controls (mean, 0.61 [micro]mol/litre; SD, 0.13). Haemodialysis significandy decreased the serum concentration by 36% (before dialysis: mean 0.99 (SD, 0.25) [micro]mol/litre). after dialysis: mean, 0.63 (SD, 0.15) [micro] Serum SDMA concentrations were higher in patients with renal failure, and haemodialysis decreased the concentration by 60%. There was no difference in serum arginine concentrations between the groups.

Conclusion--Serum concentrations of ADMA are increased in renal failure and haemodialysis reduces the concentration.

Keywords: chronic renal failure; dialysis; nitric oxide; arginine; dimethylarginines

Nitric oxide (NO), a potent chemical mediator synthesised from L-arginine by a family of NO synthases, is involved in many functions including regulation of vascular tone, neurotransmission, and host defence. [1] In the blood vessels, basal release of NO is important in the maintenance of vascular tone and blood pressure. [2] Abnormalities in NO production have been implicated in many diseases including hypertension, [3 4] pre-eclampsia, [5, 6] multiple sclerosis, [7] hypercholesterolaemia, [8] septic shock, [9] and renal failure. [10] NO is synthesised by the conversion of L-arginine to L-citrulline by the enzyme NO synthase. One of the factors determining the activity of the enzyme is the availability of the substrate L-arginine, which is transported into the cell by an amino acid transporter. The transport of L-arginine can be blocked experimentally by its analogue [N.sup.G]-methyl-L-arginine (L-NMMA). [2]

It has been suggested that endogenous analogues of L-arginine might be involved in the regulation of the in vivo production of NO. One of these, [N.sup.G],[N.sup.G]-dimethyl-L-arginine (asymmetric dimethylarginine; ADMA), has been shown to be present in human urine, plasma, [10] and tissues, [11] and to be synthesised by endothelial cells. [12] ADMA has been shown to inhibit NO synthesis in vitro [13] and has been suggested to play a role in regulating …