TY - JOUR
T1 - Regulation of nitric oxide synthesis in uraemia
AU - Arese, M.
AU - Strasly, M.
AU - Ruva, C.
AU - Costamagna, C.
AU - Ghigo, D.
AU - Mac Allister, R.
AU - Verzetti, G.
AU - Tetta, C.
AU - Bosia, A.
AU - Bussolino, Federico
PY - 1995
Y1 - 1995
N2 - Nitric oxide (NO) is a cell-to-cell mediator involved in the regulation of vascular tone and in the mechanisms of host defence. Since uraemic syndrome is characterized by abnormalities in blood pressure and flow and by impairment of white cell function, we studied the regulation of nitric oxide synthase (NOS) activity by uraemic plasma. We used three different cellular types having different levels of NOS activity: tEnd. 1 murine endothelial cell line transformed by mT oncogene of polyomavirus had a high NOS activity and expressed endothelial-NOS (eNOS) and inducible-NOS (iNOS) isoforms; human endothelial cells from cord umbilical vein (HUVEC) had low enzymatic activity and expressed only eNOS; finally, J774 murine macrophage line was characterised by iNOS induced after treatment with cytokines. We demonstrated that most (79%) of end-stage uraemic plasma studied inhibited NOS activity in tEnd.1 and in cytokine induced -J774, whereas they were ineffective on HUVEC. Twenty percent of plasma samples (14 of 67) activated NOS activity in tEnd.1 and in J774 cells, but not in HUVEC, suggesting the presence of molecule(s) which influence iNOS. The effectof plasma was not dependent on the type of haemodialysis treatment. A great number of plasmas from patients with moderate renal failure also inhibited NOS activity in tEnd.1, suggesting that the accumulation of molecules affecting NOS was caused by the renal failure rather than the haemodialytic treatment. However, the haemodialysis modified the effectof plasmas on NOS activity. Plasma taken after haemodialysis session showed a reduced inhibitory activity in tEnd.1 and in some cases it enhanced NOS activity. Simultaneously, molecules reducing NOS activity accumulated in the ultrafiltrate.The plasma concentration of NG-NGdimethyl-L-arginine (asymmetrical dimethylarginine, ADMA), an inhibitor of NOS, increased in end-stage uraemic patients and was reduced by haemodialysis. However, the concentrations reached in uraemic plasmas were lower than the ADMA ICM50on tEnd.1 NOS, indicating that this compound contributes with other molecules to the inhibitory effect of uraemic plasma. Haemodialysis reduced also the enhanced effect exerted by some plasmas on NOS in J774. Therefore, the effect of endstage uraemic plasma on NOS activity derive from the balance between inhibitors and activators.
AB - Nitric oxide (NO) is a cell-to-cell mediator involved in the regulation of vascular tone and in the mechanisms of host defence. Since uraemic syndrome is characterized by abnormalities in blood pressure and flow and by impairment of white cell function, we studied the regulation of nitric oxide synthase (NOS) activity by uraemic plasma. We used three different cellular types having different levels of NOS activity: tEnd. 1 murine endothelial cell line transformed by mT oncogene of polyomavirus had a high NOS activity and expressed endothelial-NOS (eNOS) and inducible-NOS (iNOS) isoforms; human endothelial cells from cord umbilical vein (HUVEC) had low enzymatic activity and expressed only eNOS; finally, J774 murine macrophage line was characterised by iNOS induced after treatment with cytokines. We demonstrated that most (79%) of end-stage uraemic plasma studied inhibited NOS activity in tEnd.1 and in cytokine induced -J774, whereas they were ineffective on HUVEC. Twenty percent of plasma samples (14 of 67) activated NOS activity in tEnd.1 and in J774 cells, but not in HUVEC, suggesting the presence of molecule(s) which influence iNOS. The effectof plasma was not dependent on the type of haemodialysis treatment. A great number of plasmas from patients with moderate renal failure also inhibited NOS activity in tEnd.1, suggesting that the accumulation of molecules affecting NOS was caused by the renal failure rather than the haemodialytic treatment. However, the haemodialysis modified the effectof plasmas on NOS activity. Plasma taken after haemodialysis session showed a reduced inhibitory activity in tEnd.1 and in some cases it enhanced NOS activity. Simultaneously, molecules reducing NOS activity accumulated in the ultrafiltrate.The plasma concentration of NG-NGdimethyl-L-arginine (asymmetrical dimethylarginine, ADMA), an inhibitor of NOS, increased in end-stage uraemic patients and was reduced by haemodialysis. However, the concentrations reached in uraemic plasmas were lower than the ADMA ICM50on tEnd.1 NOS, indicating that this compound contributes with other molecules to the inhibitory effect of uraemic plasma. Haemodialysis reduced also the enhanced effect exerted by some plasmas on NOS in J774. Therefore, the effect of endstage uraemic plasma on NOS activity derive from the balance between inhibitors and activators.
KW - Endothelium
KW - Haemodialysis
KW - Nitric oxide
KW - Nitric oxide synthase
KW - Uraemia
UR - http://www.scopus.com/inward/record.url?scp=0029112616&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029112616&partnerID=8YFLogxK
U2 - 10.1093/oxfordjournals.ndt.a091332
DO - 10.1093/oxfordjournals.ndt.a091332
M3 - Article
C2 - 8538931
AN - SCOPUS:0029112616
VL - 10
SP - 1386
EP - 1397
JO - Nephrology Dialysis Transplantation
JF - Nephrology Dialysis Transplantation
SN - 0931-0509
IS - 8
ER -