Acetylsalicylic acid mitigates erythropoietin-associated blood pressure increase in nonuremic rats

Abstract

Background: Approximately 30% of the chronic kidney disease patients using recombinant human erythropoietin (rhuEPO) have an increase in blood pressure (BP). Its mechanism and whether it depends on renal function remain unclear. There is early evidence that acetylsalicylic acid (ASA) prevents the rhuEPO-induced increase in BP. This study aims to verify whether very high doses of rhuEPO can increase BP in nonuremic rats and whether the co-administration of ASA can prevent it. Methods: Forty male Wistar rats were divided into four groups: placebo/placebo; placebo/rhuEPO 200 UI/kg thrice weekly; placebo/ASA 50 mg/kg daily; rhuEPO 200 UI/kg thrice weekly/ASA 50 mg/kg daily. Hematocrit was measured before and after and systolic BP was measured weekly by tail-cuff technique. Direct measurement of the BP was obtained at the end. Results: The rhuEPO groups had higher final hematocrit (rhuEPO/placebo 56.7 +/- 7.6, rhuEPO/ASA 56.7 +/- 7.7; p < 0.001 versus placebo/placebo, 42.2 +/- 4.7 and ASA/placebo 41.2 +/- 4.2); and also increase in systolic BP (rhuEPO/placebo 135.1 +/- 15.0, p = 0.01 and rhuEPO/ASA 127.2 +/- 6.8, p = 0.02), whereas BP in rats from placebo/placebo (120.9 +/- 5.0, p = 0.18) and placebo/ASA (124.6 +/- 13.3, p = 0.12) groups remained unchanged. By direct measurement, the final BP was higher in rhuEPO/placebo (DBP 123.1 +/- 12.0; SBP 157.4 +/- 12.5; MBP 139.8 +/- 11.9) than placebo/placebo (DBP 105.1 +/- 11.5; SBP 141.0 +/- 12.6; MBP 122.1 +/- 12.1) and placebo/ASA groups (DBP 106.6 +/- 8.1; SBP 141.5 +/- 8.4, MBP 122.1 +/- 7.2) (p < 0.05 by post hoc Bonferroni test ANOVA). The rhuEPO/ASA group (PAD 115.1 +/- 11.4, PAS 147.4 +/- 9.1, MBP 130.1 +/- 10.3) was not different from other groups. Conclusions: The administration of very high doses of rhuEPO is associated with an increase in hematocrit and BP in nonuremic rats. The concomitant use of ASA mitigates the rhuEPO-associated BP increase.