D. Delcastillo et al., THE PRESSOR EFFECT OF RECOMBINANT-HUMAN-ERYTHROPOIETIN IS NOT DUE TO DECREASED ACTIVITY OF THE ENDOGENOUS NITRIC-OXIDE SYSTEM, Nephrology, dialysis, transplantation, 10(4), 1995, pp. 505-508
In a subset of dialysis patients, erythropoietin (rHuEpo) treatment ex
acerbates hypertension. The mechanism of this presser effect is unknow
n; however, it has been suggested that decreased endogenous nitric oxi
de (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 excret
ion of the stable NO metabolites, nitrite (NO2) and nitrate (NO3), wer
e determined at baseline and 3 weeks. After 3 weeks of rHuEpo treatmen
t 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 presser effect, but this is not associated with de
creased activity of the endogenous NO system. Thus decreased endogenou
s NO activity is not responsible for rHuEpo-associated hypertension. T
hese data further suggest that endogenous NO activity is increased in
rHuEpo-treated rats, perhaps as a counterregulatory mechanism that lim
its the presser effect. Whether this mechanism is active in the settin
g of rHuEpo-treated chronic renal failure in humans is unknown.