Journal of the American Society of Nephrology, Vol 6, 1278-1283, Copyright © 1995 by American Society of Nephrology

REGULAR ARTICLES

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 and R Coppo
Nephrology and Dialysis Department, Regina Margherita Children's Hospital, Torino, Italy.

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)-1 beta and tumor necrosis factor-alpha (TNF-alpha) 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-1 beta and TNF-alpha 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-alpha and IL-1 beta production.

This article has been cited by other articles:

				A. Mourad, S. Carney, A. Gillies, B. Jones, R. Nanra, and P. Trevillian Acute effect of haemodialysis on arterial stiffness: membrane bioincompatibility? Nephrol. Dial. Transplant., November 1, 2004; 19(11): 2797 - 2802. [Abstract] [Full Text] [PDF]

				G. Peer, E. Itzhakov, Y. Wollman, T. Chernihovsky, I. Grosskopf, D. Segev, D. Silverberg, M. Blum, D. Schwartz, and A. Iaina Methylene blue, a nitric oxide inhibitor, prevents haemodialysis hypotension Nephrol. Dial. Transplant., July 1, 2001; 16(7): 1436 - 1441. [Abstract] [Full Text] [PDF]

				A.C. Mendes Ribeiro, T.M.C. Brunini, J.C. Ellory, and G.E. Mann Abnormalities in L-arginine transport and nitric oxide biosynthesis in chronic renal and heart failure Cardiovasc Res, March 1, 2001; 49(4): 697 - 712. [Abstract] [Full Text] [PDF]

				R. Coppo and A. Amore Importance of the bradykinin-nitric oxide synthase system in the hypersensitivity reactions of chronic haemodialysis patients Nephrol. Dial. Transplant., September 1, 2000; 15(9): 1288 - 1290. [Full Text] [PDF]

				H. Miyazaki, H. Matsuoka, H. Itabe, M. Usui, S. Ueda, S. Okuda, and T. Imaizumi Hemodialysis Impairs Endothelial Function via Oxidative Stress : Effects of Vitamin E-Coated Dialyzer Circulation, March 7, 2000; 101(9): 1002 - 1006. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673