Alterations of systemic blood pressure, serum levels of endothelin and nitric oxide under erythropoietin treatment in hemodialysis patients

Hypertension is a major complication of recombinant human erythropoietin (rHuEPO) therapy and occurs in about one third of the hemodialysis (HD) population. This study evaluated the effect of rHuEPO on serum levels of various vasoactive substances such as endothelin (ET) and nitric oxide (NOx) concentrations in HD patients. Fifteen regular HD patients with less than 25% hematocrit were enrolled in the study. rHuEPO, 3, 000U, was administered intravenously three times a week at the end of each HD session. Serum ET, NOx, thromboxane B2 (TXB2), prostacyclin (6-keto-PGF1α) and cyclic guanosine 3′, 5′-monophosphate (cGMP) levels were determined before and again 2 and 4 weeks after starting rHuEPO treatment. ET, TXB2 and 6-keto-PGF1α were measured by RIA. NOx was measured using HPLC. An increase in blood pressure over 6 mmHg was demonstrated in 7 patients (hypertensive group), whereas in 8 patients, the elevation of blood pressure was less than 5 mmHg (non-hypertensive group). Serum ET levels were increased in HD patients. An increase in serum ET remained unchanged after rHuEPO treatment in the hypertensive group, whereas the rise in serum ET levels was attenuated in the non-hypertensive group. Serum NOx levels were also increased in HD patients. The increase in serum NOx levels was blunted in hypertensive group after rHuEPO administration. However, these levels remained unchanged in the non-hypertensive group. In the non-hypertensive group, the number of platelets was significantly increased compared to that in the hypertensive group. The number of platelets was well correlated with serum NOx levels. These results suggest that rHuEPO- induced alteration of blood pressure may be due to an alteration in the serum ET/NOx ratio, and the alteration of serum NOx level may, in part, be due to an increase in platelets by rHuEPO therapy.