Effects of Erythropoietin and Erythropoietin-receptor Materials in Blood Pressure, Hematocrit and Body-Spleen Weight Variability

Adversity with erythropoietin (Epo) treatment (Epo-Rx) is grim in the cardio-cerebrovascular system. Because circadian rhythmic variability is an important aspect of cardiovascular function, we evaluated circadian blood pressure (BP), hematocrit (Hct), body and spleen weight (BW, SW) variability immediately before and after 4-week, twice-weekly course of Epo-Rx (50 U/kg) along with physiological saline (control), pure human Epo-receptor protein (Epo-bp) and anti-Epo-bp antibody (αEpo-bp) groups at midnight, 4 AM, 8 AM, noon, 4 PM and 8 PM in Sprague-Dawley rats. In our earlier report, Epo-Rx increased BP, Hct and SW markedly overall compared with saline, Epo-bp, and αEpo-bp groups (Hypertension 2007;50:439-45). In this current report, variability (%) of BP, Hct, BW and SW are compared. Epo-bp treated BP Variability (BPV) was lower than others (9.5 vs. 15.5 control and others in similar values). Phase changes were noticed when exposed to Epo (daytime peaks in Epo, Epo+Epo-bp and Epo+αEpo-bp). Hct variability (HctV) in Epo and Epo-bp treated groups shows somewhat lower than in control group (18.3 in C vs. 13.3, 12.9, and 19.4 in Epo, Epo-bp and αEpo-bp, respectively). However, Epo effect was additive to HctV when Epo was added to Epo-bp or αEpo-bp (32.0 and 30.4, respectively). All 5-study groups showed phase changes, although Epo-exposed groups had a much greater magnitude with markedly increased Hct (peak at 19:00 in control and 5 study groups during the daytime through noon-hour peaks). BW variability is similar in each group (except lower BW in the Epo-group) with various peak hours but SW variability (SWV) showed a similar pattern as shown in HctV. Best treatment times for Epo, Epo+Epo-bp and Epo+αEpo-bp were estimated: BP at 4 PM, 4 AM and 4 AM, respectively; Hct at 4 AM and both at midnight, respectively; SW at midnight, 8 PM and noon, respectively. Thus, significantly increased BPV, HctV and SWV in Epo-Rx than those of other groups and extremely increased Hct resulted in splenomegaly.