SERUM LEVELS OF N-G,N-G-DIMETHYL-L-ARGININE, A POTENTIAL ENDOGENOUS NITRIC-OXIDE INHIBITOR IN DIALYSIS PATIENTS

Nitric oxide (NO) is involved in blood pressure regulation, and its sy nthesis is inhibited by methylarginines. It has been hypothesized that one of these, asymmetrical dimethylarginine (ADMA), may contribute to dialysis-associated hypertension because it accumulates in the plasma of hemodialysis (HD) patients in a concentration high enough (4 mu mo l/L) to inhibit NO synthesis in experimental model systems. A precolum n HPLC technique was used to quantify methylarginines (ADMA and symmet rical dimethylarginine [SDMA]) in plasma from HD patients before and a fter dialysis, from continuous ambulatory peritoneal dialysis (CAPD) p atients, and from healthy subjects. Plasma ADMA concentrations were 0. 59 +/- 0.22 (SD) mu mol/L in HD patients predialysis (n = 19) and 0.70 +/- 0.27 mu mol/L in CAPD patients (n = 11), versus about half of the concentration in control subjects (0.36 +/- 0.08 mu mol/L, n = 7). Th e concentrations of SDMA (not an inhibitor of NO formation) were appro ximately four to five times the ADMA concentrations in both HD and CAP D patients, in contrast to a ratio of 1:1 in the control subjects. Met hylarginine concentrations were reduced by 23% and 40% postdialysis, a s calculated from ADMA and SDMA values, respectively. No significant c orrelations were observed between ADMA concentrations, on the one hand , and blood pressure, creatinine and dialysis dose (Kt/V urea), on the other hand. It is concluded that plasma levels of ADMA are considerab ly lower than those reported earlier in patients treated with HD and a lso below the levels that hitherto have been thought to have clinical relevance. The role of ADMA in inhibiting NO in dialysis-associated hy pertension is questioned.