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L-arginine, the precursor of nitric oxide, abolishes the effect of estrogens on bleeding time in experimental uremia.

Abstract
We have reported previously that conjugated estrogens that are effective in shortening the prolonged bleeding time in uremic patients are also effective on bleeding time in a rat model of uremia. Using such a rat model we have recently demonstrated that nitric oxide (NO), an endothelium-derived vasodilator, is involved in mediating the bleeding tendency of uremia. With the present study we wanted to investigate whether conjugated estrogen mixture or its active component, 17 beta-estradiol, reduce uremic bleeding by interfering with the NO pathway. Our results showed that the shortening effect of conjugated estrogen and 17 beta-estradiol on bleeding time of uremic rats was completely reversed by giving the animals the NO precursor L-arginine, but not D-arginine, which is not a precursor of NO. Dexamethasone which at variance to progesterone inhibits the process of induction of NO-forming enzyme, shortened the prolonged bleeding time of uremic rats within 4 hours from injection. This effect was eliminated by L-arginine but not D-arginine administration. The glucocorticoid receptor antagonist cortexolone prevented the shortening of bleeding time induced by dexamethasone, suggesting that a receptor-mediated mechanism is involved in the hemostatic effect of dexamethasone as previously reported for estrogens. Unlike conjugated estrogens and dexamethasone, progesterone had no effect on bleeding time. All these findings would indicate that the effect of estrogens and dexamethasone on primary hemostasis in uremia might be mediated by changes in NO synthetic pathway.
AuthorsC Zoja, M Noris, D Corna, G Viganò, N Perico, G de Gaetano, G Remuzzi
JournalLaboratory investigation; a journal of technical methods and pathology (Lab Invest) Vol. 65 Issue 4 Pg. 479-83 (Oct 1991) ISSN: 0023-6837 [Print] United States
PMID1656142 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Estrogen Antagonists
  • Estrogens, Conjugated (USP)
  • Nitric Oxide
  • Dexamethasone
  • Arginine
  • Cortodoxone
Topics
  • Animals
  • Arginine (pharmacology)
  • Bleeding Time
  • Cortodoxone (pharmacology)
  • Dexamethasone (pharmacology)
  • Disease Models, Animal
  • Estrogen Antagonists (pharmacology)
  • Estrogens, Conjugated (USP) (pharmacology)
  • Male
  • Nitric Oxide (metabolism)
  • Rats
  • Rats, Inbred Strains
  • Uremia (blood)

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