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

Abstract

The objective of this study was to determine intradialytic blood levels of nitric oxide (NO), in patients undergoing chronic haemodialysis. This was done by detection of nitrosylhaemoglobin by a sensitive technique of spin trap electron paramagnetic resonance at 0, 5, 15, 60, 180 and 240 min of a 4-h standard bicarbonate dialysis, using the same dose (6000 U) of heparin and different dialysis membranes. The study group included 12 patients treated with cellulose-derived dialysis membranes (nine with cuprophan and three with cellulose triacetate) and 10 patients treated with synthetic membranes (five with polysulfone and five with polymethylmethacrylate). Control groups included 11 normal subjects and six patients with end-stage renal failure who were receiving intermittent peritoneal dialysis. Basal blood levels of nitrosylhaemoglobin in haemodialysis patients were significantly higher than normals, but similar to peritoneal dialysis patients. A significant increase (P < 0.01) in nitrosylhaemoglobin level was detected at 15 min of haemodialysis irrespective of the membrane used. A decrease to basal levels at 180 min was observed in all but two cuprophan-treated patients who, in contrast to the others, had a symptomatic hypotension at the end of the session and a further increase in blood nitric oxide. Patients undergoing peritoneal dialysis did not show any change in blood levels of nitrosylhaemoglobin during the first 180 min of the procedure. Thus, a constant increase in nitrosylhaemoglobin levels was observed early in haemodialysis, but not in peritoneal dialysis patients. Very preliminary evidence was obtained for a role of nitric oxide in the vascular instability at the end of haemodialysis in a few patients who had hypotensive episodes.

Indices of activity of the nitric oxide system in hemodialysis patients

“…16 The extent to which this occurs in our study is uncertain because our HD patients were dialyzed with biocompatible membranes, which have low inducible NOS-activating potential. [16][17][18] However, some intradialytic NO production may occur even with biocompatible dialyzers, and if that occurred in the present study, the amount of physiologically regulated NO produced in HD patients would be even less than suggested by the reduced NO x output.…”

“…16 The extent to which this occurs in our study is uncertain because our HD patients were dialyzed with biocompatible membranes, which have low inducible NOS-activating potential. [16][17][18] However, some intradialytic NO production may occur even with biocompatible dialyzers, and if that occurred in the present study, the amount of physiologically regulated NO produced in HD patients would be even less than suggested by the reduced NO x output.Despite evidence from the NO x output data that NO production is reduced in HD patients, plasma NO x levels measured after strict dietary nitrate restriction and after an overnight fast were much greater in pre-HD patients compared with controls. This does not contradict the NO x output data because NO x in the body of the patients with ESRD (whether exogenous or endogenous) has accumulated in the plasma for 44 hours since the previous HD.…”

The effects of renal replacement therapy on plasma, asymmetric dimethylarginine, nitric oxide and C-reactive protein levels

“…13 However, the relationship between endothelial dysfunction of uremia has reached contradictory conclusions. Some authors found to be increased NO levels in uremia 14,15 , but contrary results have been reported which is explained by increase in ADMA levels. 16,17 Recently, whole-body NO production has been determined by radionuclide-based measurement of arginine to citrullin conversion and reduced release of NO has been reported in ureamic patients compared with matched control subjects.…”

Hemodialysis Impairs Endothelial Function via Oxidative Stress

“…There may be decreased endothelial NO formation by endogenous NO synthase inhibitors, which are accumulated in patients in end-stage renal disease, 34 -36 or by increased inactivation of NO by reactive oxygen species. 15 The former possibility is unlikely, because recent findings have consistently advocated that NO production during hemodialysis is increased rather than decreased [37][38][39] and endogenous NO synthase inhibitors are eliminated by hemodialysis. 34 Hemodialysis may inactivate NO by generating reactive oxygen species on the surface of dialysis membranes by activation of polymorphonuclear leukocytes.…”