Enhanced production of nitric oxide by blood-dialysis membrane interaction

A. Amore, R. Bonaudo, D. Ghigo, M. Arese, C. Costamagna, P. Cirina, B. Gianoglio, L. Perugini, R. Coppo

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Nitric oxide (NO) is a powerful vasoactive product of endothelial origin, and one of its major effects is vasodilation, leading to hypotension. The role of NO in some complications of uremia is still debated. This 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 polymethylmethacrylate membranes. Blood samples from a healthy donor after recirculation for 0, 5, 15, 30, and 60 min were coincubated for 6 h with a murine endothelial cell line (t.End.1); mRNA for inducible NO synthase and enzyme activity, measured as (3H)citrulline produced from (3H)arginine, were detected. The release of interleukin (IL)-1β and tumor necrosis factor-alpha (TNF-α) from recirculating lymphomonocytes was measured, too. The NO synthase activity of endothelial cells was stimulated by blood dialyzed with cuprophan, peaking at 15 min (11-fold increase in comparison to the basal values), whereas polymethylmethacrylate was ineffective (P <0.01 versus Cuprophan). Dialysis with cuprophan, but not with polymethylmethacrylate, induced in endothelial cells the expression of mRNA encoding for inducible NO synthase. The release of IL-1β and TNF-α after 6 h by recirculating lymphomonocytes 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 endothelial NO synthase can be enhanced during the dialysis sessions by the interaction of lymphomonocytes with the membranes, possibly via TNF-α and IL-1β production.

Original languageEnglish
Pages (from-to)1278-1283
Number of pages6
JournalJournal of the American Society of Nephrology
Issue number4
Publication statusPublished - 1995


  • Biocompatibility
  • Cytokines
  • Dialysis complications
  • Dialysis membranes
  • Nitric oxide

ASJC Scopus subject areas

  • Nephrology


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