17β-Estradiol corrects hemostasis in uremic rats by limiting vascular expression of nitric oxide synthases

Marina Noris, Marta Todeschini, Sergio Zappella, Samantha Bonazzola, Carla Zoja, Daniela Corna, Flavio Gaspari, Franco Marchetti, Sistiana Aiello, Giuseppe Remuzzi

Research output: Contribution to journalArticlepeer-review

Abstract

Conjugated estrogens shorten the prolonged bleeding time in uremic patients and are similarly effective in a rat model of uremia. We have previously demonstrated that the shortening effect of a conjugated estrogen mixture or 17β-estradiol on bleeding time was abolished by the nitric oxide (NO) precursor L-arginine, suggesting that the effect of these drugs on hemostasis in uremia might be mediated by changes in the NO synthetic pathway. The present study investigated the biochemical mechanism(s) by which conjugated estrogens limit the excessive formation of NO. 17β-estradiol (0.6 mg/kg), given to rats made uremic by reduction of renal mass, significantly reduced bleeding time within 24 h and completely normalized plasma concentrations of the NO metabolites, nitrites and nitrates, and of NO synthase (NOS) catalytic activity, determined by NADPH-diaphorase staining in the thoracic aorta. Endothelial NOS (ecNOS) and inducible NOS (iNOS) immunoperoxidase staining in the endothelium of uremic aortas of untreated rats was significantly more intense than in control rats, while in uremic rats receiving 17β-estradiol staining was comparable to controls. Thus 17β-estradiol corrected the prolonged bleeding time of uremic rats and fully normalized the formation of NO by reducing the expression of ecNOS and iNOS in vascular endothelium. These results provide a possible biochemical explanation of the well-known effect of estrogens on primary hemostasis in uremia, in experimental animals and humans.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume279
Issue number4 48-4
Publication statusPublished - 2000

Keywords

  • Bleeding time
  • Chronic renal failure
  • Conjugated estrogens
  • Endothelium

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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