Role of endothelium-derived nitric oxide in the bleeding tendency of uremia

Giuseppe Remuzzi, Norberto Perico, Carla Zoja, Daniela Corna, Daniela Macconi, Gianluigi Viganò

Research output: Contribution to journalArticlepeer-review

Abstract

Endothelium-derived relaxing factor, now identified as nitric oxide (NO), is a labile humoral agent formed by vascular endothelial cells from L-arginine. NO mediates the action of substances that induce endothelium-dependent relaxation and plays a role in regulating blood pressure. In this study we investigated whether NO is involved in the pathogenesis of the bleeding tendency associated with renal failure. Rats with extensive surgical ablation of renal mass develop renal insufficiency due to progressive glomerulosclerosis. Like uremic humans, rats with renal mass reduction and uremia have a bleeding tendency that manifests itself by a prolonged bleeding time. We found that N-monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO formation from L-arginine, completely normalized bleeding time when given to uremic rats. L-NMMA injection also increased ex vivo platelet adhesion but did not affect ex vivo platelet aggregation induced by adenosine diphosphate, arachidonic acid, and calcium ionophore A23187. The shortening effect of L-NMMA on bleeding time was completely reversed by giving the animals the NO precursor L-arginine, but not D-arginine, which is not a precursor of NO. It thus appears that NO is a mediator of the bleeding tendency of uremia.

Original languageEnglish
Pages (from-to)1768-1771
Number of pages4
JournalJournal of Clinical Investigation
Volume86
Issue number5
Publication statusPublished - Nov 1990

Keywords

  • Bleeding time
  • L-arginine
  • N-monomethyl-L-arginine
  • Platelet adhesion
  • Uremic rats

ASJC Scopus subject areas

  • Medicine(all)

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