BACKGROUND: We previously demonstrated that bicarbonate dialysis solutions incubated with endothelial cells (EC) enhance nitric oxide synthase (NOS). We then investigated whether blood circulated in simulated dialysis circuits triggers inflammatory and apoptotic mediators in vessel wall cells, aiming to compare the effects of bicarbonate hemodialysis (BHD) and acetate-free biofiltration (AFB). METHODS: Blood units from 22 healthy donors were dialyzed on AN69 with BHD in 11 sessions and AFB in another 11 sessions. Each dialysate remained endotoxin-free during the 60 min of dialysis. Blood samples having been re-circulated for 15 and 60 min were incubated with EC and smooth muscle cells (SMC), which were then investigated for NOS activity (3H citrulline production from 3H arginine), mRNAs transcription of the inducible isoforms of NOS (iNOS) and cyclooxygenase (COX-2) and the pro-apoptotic p53 protein. To investigate cell-cell interactions, in an-other series of 16 simulated dialyses, lympho-monocytes from blood circulated in either BHD or AFB were incubated with EC co-cultured in transwell devices with SMC. NOS activity was measured in EC and SMC. RESULTS: In comparison to AFB, blood circulated in BHD induced a significantly greater enhancement of NOS activity in EC, SMC and mRNAs transcription of pro-inflammatory iNOS, COX-2 and pro-apoptotic p53 (for each BHD data series p < 0.01 to p < 0.0001 vs. AFB). Lympho-monocytes from blood circulated in BHD but not in AFB, triggered the final SMC activation. CONCLUSIONS: Ex vivo AFB is less effective than BHD in activating vessel wall cells to synthesis/release of pro-inflammatory and pro-apoptotic mediators.
BACKGROUND: We previously demonstrated that bicarbonate dialysis solutions incubated with endothelial cells (EC) enhance nitric oxide synthase (NOS). We then investigated whether blood circulated in simulated dialysis circuits triggers inflammatory and apoptotic mediators in vessel wall cells, aiming to compare the effects of bicarbonate hemodialysis (BHD) and acetate-free biofiltration (AFB). METHODS: Blood units from 22 healthy donors were dialyzed on AN69 with BHD in 11 sessions and AFB in another 11 sessions. Each dialysate remained endotoxin-free during the 60 min of dialysis. Blood samples having been re-circulated for 15 and 60 min were incubated with EC and smooth muscle cells (SMC), which were then investigated for NOS activity (3H citrulline production from 3H arginine), mRNAs transcription of the inducible isoforms of NOS (iNOS) and cyclooxygenase (COX-2) and the pro-apoptotic p53 protein. To investigate cell-cell interactions, in an-other series of 16 simulated dialyses, lympho-monocytes from blood circulated in either BHD or AFB were incubated with EC co-cultured in transwell devices with SMC. NOS activity was measured in EC and SMC. RESULTS: In comparison to AFB, blood circulated in BHD induced a significantly greater enhancement of NOS activity in EC, SMC and mRNAs transcription of pro-inflammatory iNOS, COX-2 and pro-apoptotic p53 (for each BHD data series p < 0.01 to p < 0.0001 vs. AFB). Lympho-monocytes from blood circulated in BHD but not in AFB, triggered the final SMC activation. CONCLUSIONS: Ex vivo AFB is less effective than BHD in activating vessel wall cells to synthesis/release of pro-inflammatory and pro-apoptotic mediators.