ENHANCED PRODUCTION OF NITRIC-OXIDE BY BLOOD-DIALYSIS MEMBRANE INTERACTION

Nitric oxide (NO) is a powerful vasoactive product of endothelial orig in, and one of its major effects is vasodilation, leading to hypotensi on. The role of NO in some complications of uremia is still debated. T his study evaluated whether endothelial NO synthase activity could be modulated by the exposure of healthy blood to hemodialysis materials. In vitro hemodialysis sessions were performed with cuprophan and polym ethylmethacrylate membranes. Blood samples from a healthy donor after recirculation for 0, 5, 15, 30, and 60 min were coincubated for 6 h wi th a murine endothelial cell line (t.End.1); mRNA for inducible NO syn thase and enzyme activity, measured as (H-3)citrulline produced from ( H-3)arginine, were detected. The release of interleukin (IL)-1 beta an d tumor necrosis factor-alpha (TNF-alpha) from recirculating lymphomon ocytes was measured, too. The NO synthase activity of endothelial cell s was stimulated by blood dialyzed with cuprophan, peaking at 15 min ( 11-fold increase in comparison to the basal values), whereas polymethy lmethacrylate was ineffective (P < 0.01 versus Cuprophan). Dialysis wi th cuprophan, but not with polymethylmethacrylate, induced in endothel ial cells the expression of mRNA encoding for inducible NO synthase. T he release of IL-1 beta and TNF-alpha after 6 h by recirculating lymph omonocytes paralleled the NO synthase activity profile in endothelial cells and was significantly higher after cuprophan exposure than after polymethylmethacrylate (P < 0.0001). In conclusion, the activity of e ndothelial NO synthase can be enhanced during the dialysis sessions by the interaction of lymphomonocytes with the membranes, possibly via T NF-alpha and IL-1 beta production.