Phase 2 Study of Single High-Dose Palifermin for Graft-Versus-Host Disease Prevention after Matched Unrelated Donor Transplantation

Administration of recombinant erythropoietin (rEPO) is often associated with systemic and pulmonary arterial hypertension in animals and human. The present study was conducted to determine whether one-week rEPO-treatment can produce any effect on pulmonary vasomotor function.Male Wistar rats were injected with rEPO (400 IU/kg sc) or saline every other day for one week. Tension, biochemical and Real-Time PCR experiments were conducted on left and right branches of pulmonary artery and main pulmonary artery isolated from the rats.ACh-induced relaxation was significantly (p < 0.05) reduced in rEPO-treated rats in comparison to control animals. Relaxation to the NO donor SNP was not different between the groups. EDHF-induced relaxation was remarkably higher in rEPO-treated group in comparison to control. Phenylephrine-induced contraction was significantly (p < 0.05) reduced in rings from rEPO-treated rats at the second and third lowest concentrations of phenylephrine and its potency was not significantly reduced. No significant difference was observed in CaCl2-induced contraction between the groups. Nitric oxide production was significantly reduced in rEPO-treated rats in comparison to control animals. Real-time PCR studies demonstrated a significant decrease (p < 0.05) of eNOS transcript. However, peNOS activity was not altered with rEPO treatment.The present study suggests that EPO-treatment for one week attenuates ACh-stimulated NO production. It does not affect the vasodilatory action of SNP. It showed up-regulation of EDHF and decreased potency of phenylephrine. Thus elevated EPO may diversely affect the vasomotor function of pulmonary artery. Clinically, it is important to observe the use of EPO in hypertensive condition.