Early increase in blood nitric oxide, detected by electron paramagnetic resonance as nitrosylhaemoglobin, in haemodialysis.

Abstract The objective of this study was to determine Key words: nitric oxide; biocompatibility; dialysisintradialytic blood levels of nitric oxide (NO), membranes; electron paramagnetic resonancein patients undergoing chronic haemodialysis. Thiswas done by detection of nitrosylhaemoglobinby a sensitive technique of spin trap electron paramag- Introduction netic resonance at 0, 5, 15, 60, 180 and 240 minof a 4-h standard bicarbonate dialysis, using the same Vascular endothelial cells [1] and several other celldose (6000 U) of heparin and different dialysis mem- lines, including phagocytes [2], synthesize and releasebranes. The study group included 12 patients treated nitric oxide (NO). NO counterbalances the vasocon-with cellulose-derived dialysis membranes (nine with strictor action of endothelin (ET-1) and inhibits ET-1cuprophan and three with cellulose triacetate) production via a cGMP-dependent pathway [3,4].and 10 patients treated with synthetic membranes (five Evidence of a role for NO in diverse physiologic andpathologic processes is emerging [2]. The capability ofwith polysulfone and five with polymethylmethacryl-this molecule to oxidize critical compounds, i.e. thiols,ate). Control groups included 11 normal subjectshaeme groups and iron sulphurs, sustains its involve-and six patients with end-stage renal failure who werement in different biological processes. Besides vasodil-receiving intermittent peritoneal dialysis. Basal bloodatation, its functions include inhibition of plateletlevels of nitrosylhaemoglobin in haemodialysis patientsaggregation and modulation of inflammatory andwere significantly higher than normals, but similarimmune processes [2,5,6].to peritoneal dialysis patients. A significant increase Plasma concentrations of arginine, the endogenous(P<0.01) in nitrosylhaemoglobin level was detected substrate of NO synthase, have been reported to beat 15 min of haemodialysis irrespective of the mem- lower [7] or higher [8] than normal in uraemia.brane used. A decrease to basal levels at 180 min Moreover, it has been reported that uraemic plasmawas observed in all but two cuprophan-treated patients contains an endogenous compound, NG, NG-dimethyl-who, in contrast to the others, had a symptomatic arginine, able to inhibit NO synthesis by interferinghypotension at the end of the session and a further with the l-arginine/NO pathway [9]. However, expo-increase in blood nitric oxide. Patients undergoing sure of cultured human endothelial cells to uraemicperitoneal dialysis did not show any change in blood plasma results in potent induction of NO formationlevels of nitrosylhaemoglobin during the first 180 [8]. Besides an increased availability of substrate,min of the procedure. Thus, a constant increase in which is still a matter of debate [7,8], it has beennitrosylhaemoglobin levels was observed early in proposed that high plasma levels of cytokines, as ahaemodialysis, but not in peritoneal dialysis patients. consequence of monocyte activation by dialysis mem-Very preliminary evidence was obtained for a role of brane [10], enhance NO formation contributing tonitric oxide in the vascular instability at the end of haemodialysis (HD) hypotension. The involvement ofhaemodialysis in a few patients who had hypotensive NO production in haemodialysis-induced hypotensionepisodes. was eventually confirmed by detecting NO2and NO3[11]. However, no data on intradialytic fluctuations ofNO blood levels in HD patients have been reported todate. Therefore, 22 patients, carefully selected forabsence of intercurrent illnesses, entered a study aimedto detect basal values and intradialytic profiles ofnitrosylhaemoglobin, as a surrogate marker of NO