Key result
Recombinant human erythropoietin significantly increased blood pressure in rats, but this was associated with increased rather than decreased urinary NO metabolites.
Why the study?
The mechanism of erythropoietin-induced hypertension is unknown, with a hypothesis that decreased endogenous nitric oxide activity may contribute.
Does recombinant human erythropoietin cause a pressor effect by decreasing endogenous nitric oxide activity in Sprague-Dawley rats?
Does recombinant human erythropoietin cause a pressor effect by decreasing endogenous nitric oxide activity in Sprague-Dawley rats?
The pressor effect of recombinant human erythropoietin in rats is not caused by decreased endogenous nitric oxide activity, which actually increases, possibly as a counter-regulatory mechanism.
Answers are grounded in this paper and cite their sources.
Erythropoietin raises BP in rats despite increased NO metabolites; leaves open alternative mechanisms and human relevance.
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.
No takes yet. Share an insight, caveat, or question.
Castillo et al. (1995) studied Normal rats (investigating rHuEpo-associated hypertension). Recombinant human erythropoietin (rHuEpo) vs. Corresponding vehicle was evaluated on Blood pressure, haematocrit, and urinary excretion of NO2 and NO3. Recombinant human erythropoietin significantly increased blood pressure in rats, but this was associated with increased rather than decreased urinary NO metabolites.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: