Chronic erythropoietin treatment enhances endogenous nitric oxide production in rats

H. Tsukahara, M. Hiraoka, C. Hori, I. Hata, T. Okada, F. Gejyo, M. Sudo

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Abstract

To examine the effect of chronic administration of recombinant human erythropoietin (rHuEPO) on endogenous nitric oxide (NO) activity, we treated Sprague-Dawley rats with rHuEPO (100 IU kg-1 or 300 IU kg-1) or a corresponding vehicle for 2 weeks, administered subcutaneously on alternate days. Treatment elicited increases in haematocrit and systolic blood pressure in a dose-dependent fashion. Simultaneous administration of N(G)-nitro-L-arginine methyl ester (L-NAME, 20 mg dl-1 of drinking water), but not aminoguanidine (400 mg dl-1), induced a further significant rise in blood pressure. The effect of L-NAME was inhibited by a large dose of L-arginine (2.0 g dl-1). Polycythaemia and hypertension induced by chronic rHuEPO therapy were associated with increased urinary NO2- and NO3- (NOx-) excretion, while co-administration of L-NAME, but not aminoguanidine, reduced NOx- excretion. Our results indicate that chronic rHuEPO treatment has a significant presser effect, but induces a compensatory increase in the steady-state release of NO by constitutive NO synthase in normal rats. Such enhanced NO synthesis may act as a protective mechanism against the hypertensive effect of rHuEPO.

Original languageEnglish
Pages (from-to)487-493
Number of pages7
JournalScandinavian Journal of Clinical and Laboratory Investigation
Volume57
Issue number6
DOIs
Publication statusPublished - Jan 1 1997
Externally publishedYes

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Keywords

  • Endogenous nitric oxide activity
  • Hypertension
  • NO and NO
  • Nitric oxide synthase inhibitors
  • Recombinant human erythropoietin

ASJC Scopus subject areas

  • Clinical Biochemistry

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