Tsukahara H, Hiraoka M, Hori C, Hata I, Okada T, Gejyo F, Sudo M
Department of Pediatrics, Fukui Medical School, Japan.
Scand J Clin Lab Invest. 1997 Oct;57(6):487-93. doi: 10.3109/00365519709084598.
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 NG-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 pressor 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.
