The pressor effect of recombinant human erythropoietin is not due to decreased activity of the endogenous nitric oxide system.
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.
del Castillo
D
D
Department of Medicine, Veterans Affairs Medical Center, Minneapolis, MN, USA.
Raij
L
L
Shultz
P J
PJ
Tolins
J P
JP
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000627:therapeutic use*; D006400:Hematocrit; D006863:Hydrogen-Ion Concentration; D006977:Hypertension, Renal / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D008297:Male; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000652:urine*; D009573:Nitrites / Q000652:urine; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use
D009566:Nitrates; D009573:Nitrites; D011994:Recombinant Proteins; D004921:Erythropoietin; D009569:Nitric Oxide