Division of Pharmacology and Toxicology, ICAR-Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
Division of Pharmacology and Toxicology, ICAR-Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
Pharmacol Rep. 2017 Aug;69(4):658-665. doi: 10.1016/j.pharep.2017.02.003. Epub 2017 Feb 4.
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 (400IU/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 CaCl-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.
重组促红细胞生成素（rEPO）的给药常与动物和人类的全身和肺动脉高血压相关。本研究旨在确定一周的 rEPO 治疗是否会对肺血管舒缩功能产生任何影响。
雄性 Wistar 大鼠每隔一天接受 rEPO（400IU/kg sc）或生理盐水注射，共一周。从大鼠中分离出左、右肺动脉分支和主肺动脉，进行张力、生化和实时 PCR 实验。
与对照组相比，rEPO 治疗组的 ACh 诱导松弛显著降低（p<0.05）。各组之间对 NO 供体 SNP 的松弛无差异。与对照组相比，rEPO 治疗组的 EDHF 诱导松弛显著增加。rEPO 治疗组在第二和第三低浓度的苯肾上腺素诱导的收缩显著降低（p<0.05），其效力没有显著降低。两组之间 CaCl 诱导的收缩没有观察到显著差异。与对照组相比，rEPO 治疗组的一氧化氮产生显著减少。实时 PCR 研究表明 eNOS 转录显著降低（p<0.05）。然而，rEPO 治疗并没有改变 peNOS 活性。
本研究表明，rEPO 治疗一周可减弱 ACh 刺激的 NO 产生。它不影响 SNP 的血管舒张作用。它显示 EDHF 的上调和苯肾上腺素的效力降低。因此，升高的 EPO 可能会对肺动脉的血管舒缩功能产生不同的影响。临床上，观察 EPO 在高血压情况下的使用很重要。
