The pressor effect of recombinant human erythropoietin is not due to decreased activity of the endogenous nitric oxide system.

Abstract

In a subset of dialysis patients, erythropoietin (rHuEpo) treatment exacerbates hypertension. The mechanism of this pressor effect is unknown; however, it has been suggested that decreased endogenous nitric oxide (NO) activity may play a role. To explore this hypothesis, Sprague-Dawley rats were given rHuEpo (150 U/kg s.c. three times per week) or corresponding vehicle. Blood pressure, haematocrit, and urinary excretion of the stable NO metabolites, nitrite (NO2) and nitrate (NO3), were determined at baseline and 3 weeks. After 3 weeks of rHuEpo treatment there was a significant increase in blood pressure and haematocrit, while in vehicle-treated rats blood pressure and haematocrit remained at basal levels. Urinary excretion of NO2+NO3 increased compared to basal in rHuEpo, but not vehicle rats. Thus in normal rats rHuEpo does have a significant pressor effect, but this is not associated with decreased activity of the endogenous NO system. Thus decreased endogenous NO activity is not responsible for rHuEpo-associated hypertension. These data further suggest that endogenous NO activity is increased in rHuEpo-treated rats, perhaps as a counter-regulatory mechanism that limits the pressor effect. Whether this mechanism is active in the setting of rHuEpo-treated chronic renal failure in humans is unknown.