Increased nitric oxide production in platelets from severe chronic renal failure patients

Can J Physiol Pharmacol. 2011 Feb;89(2):97-102. doi: 10.1139/y10-111.


Nitric oxide (NO) production occurs through oxidation of the amino acid L-arginine by NO synthase (NOS). NO inhibits platelet activation by increasing the levels of cyclic guanosine monophosphate (cGMP), thus maintaining vascular homeostasis. Our group previously demonstrated (da Silva et al. 2005) an enhancement of the L-arginine-NO-cGMP pathway in platelets taken from chronic renal failure (CRF) patients on haemodialysis associated with reduced platelet aggregation. We investigate the platelet L-arginine-NO-cGMP pathway, platelet function, and inflammation from patients in CRF on conservative treatment. A total of 42 CRF patients and 42 controls (creatinine clearance = 27 ± 3 vs. 93 ± 1 mL per min per 1.73 m2, respectively) participated in this study. NOS activity and expression and cGMP concentration were measured in platelets. Platelet aggregation induced by collagen or ADP was evaluated and plasma levels of fibrinogen were determined by the Clauss method. A marked increase in basal NOS activity was seen in undialysed CRF patients compared with controls, accompanied by an elevation of fibrinogen plasma levels. There were no differences in expression of NOS and in cGMP levels. In this context, platelet aggregation was not affected. We provide the first evidence of increased intraplatelet NO biosynthesis in undialysed CRF patients, which can be an early marker of future haemostatic abnormalities during dialysis treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Arginine / blood
  • Blood Platelets / metabolism*
  • Case-Control Studies
  • Collagen / pharmacology
  • Cyclic GMP / blood
  • Female
  • Fibrinogen / metabolism
  • Humans
  • Inflammation / blood
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / enzymology
  • Male
  • Middle Aged
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide / blood*
  • Nitric Oxide Synthase Type II / biosynthesis
  • Nitric Oxide Synthase Type II / blood
  • Nitric Oxide Synthase Type III / biosynthesis
  • Nitric Oxide Synthase Type III / blood
  • Platelet Aggregation / drug effects


  • Nitric Oxide
  • Adenosine Diphosphate
  • Fibrinogen
  • Collagen
  • Arginine
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Cyclic GMP