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| REGULATION OF NITRIC-OXIDE SYNTHESIS IN UREMIA |
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| Author(s): ARESE M, STRASLY M, RUVA C, COSTAMAGNA C, GHIGO D, MACALLISTER R, VERZETTI G, TETTA C, BOSIA A, BUSSOLINO F |
| Source: NEPHROLOGY DIALYSIS TRANSPLANTATION Volume: 10 Issue: 8 Pages: 1386-1397 Published: 1995 |
| Times Cited: 49 References: 47 |
| 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 effect of 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 effect of 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 N-G-N-G dimethyl-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 fewer than the ADMA IC50 on 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.
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| Document Type: Article |
| Language: English |
Addresses:
1. UNIV TURIN, DIPARTIMENTO GENET BIOL & CHIM MED, I-10126 TURIN, ITALY
2. OSPED NOVARA, DIV NEPHROL & DIALYSIS, NOVARA, ITALY
3. UNIV LONDON ST GEORGES HOSP, DEPT PHARMACOL & CLIN PHARMACOL, LONDON, ENGLAND
4. BELLCO SPA, LAB & CLIN RES DEPT, MIRANDOLA, ITALY |
| Publisher: OXFORD UNIV PRESS UNITED KINGDOM, WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP |
| Subject Category: Transplantation; Urology & Nephrology |
| IDS Number: RR980 |
| ISSN: 0931-0509 |
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