Regulation of nitric oxide synthesis in uraemia

M. Arese, M. Strasly, C. Ruva, C. Costamagna, D. Ghigo, R. Mac Allister, G. Verzetti, C. Tetta, A. Bosia, Federico Bussolino

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1386-1397
Number of pages12
JournalNephrology Dialysis Transplantation
Volume10
Issue number8
DOIs
Publication statusPublished - 1995

Fingerprint

Uremia
Nitric Oxide Synthase
Nitric Oxide
Renal Dialysis
Renal Insufficiency
Cytokines
Polyomavirus
Nitric Oxide Synthase Type III
Human Umbilical Vein Endothelial Cells
Nitric Oxide Synthase Type II
Oncogenes
Blood Vessels
Arginine
Protein Isoforms

Keywords

  • Endothelium
  • Haemodialysis
  • Nitric oxide
  • Nitric oxide synthase
  • Uraemia

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Regulation of nitric oxide synthesis in uraemia. / Arese, M.; Strasly, M.; Ruva, C.; Costamagna, C.; Ghigo, D.; Mac Allister, R.; Verzetti, G.; Tetta, C.; Bosia, A.; Bussolino, Federico.

In: Nephrology Dialysis Transplantation, Vol. 10, No. 8, 1995, p. 1386-1397.

Research output: Contribution to journalArticle

Arese, M, Strasly, M, Ruva, C, Costamagna, C, Ghigo, D, Mac Allister, R, Verzetti, G, Tetta, C, Bosia, A & Bussolino, F 1995, 'Regulation of nitric oxide synthesis in uraemia', Nephrology Dialysis Transplantation, vol. 10, no. 8, pp. 1386-1397. https://doi.org/10.1093/oxfordjournals.ndt.a091332
Arese, M. ; Strasly, M. ; Ruva, C. ; Costamagna, C. ; Ghigo, D. ; Mac Allister, R. ; Verzetti, G. ; Tetta, C. ; Bosia, A. ; Bussolino, Federico. / Regulation of nitric oxide synthesis in uraemia. In: Nephrology Dialysis Transplantation. 1995 ; Vol. 10, No. 8. pp. 1386-1397.
@article{78bea7047401448ba21577c1eaa1cadf,
title = "Regulation of nitric oxide synthesis in uraemia",
abstract = "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.",
keywords = "Endothelium, Haemodialysis, Nitric oxide, Nitric oxide synthase, Uraemia",
author = "M. Arese and M. Strasly and C. Ruva and C. Costamagna and D. Ghigo and {Mac Allister}, R. and G. Verzetti and C. Tetta and A. Bosia and Federico Bussolino",
year = "1995",
doi = "10.1093/oxfordjournals.ndt.a091332",
language = "English",
volume = "10",
pages = "1386--1397",
journal = "Nephrology Dialysis Transplantation",
issn = "0931-0509",
publisher = "Oxford University Press",
number = "8",

}

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 -