Kanagy Nancy L, Perrine Michael F, Cheung Dora K, Walker Benjimen R
Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque 87131-0218, USA.
J Cardiovasc Pharmacol. 2003 Oct;42(4):527-33. doi: 10.1097/00005344-200310000-00011.
This study was designed to determine whether recombinant human erythropoietin (rHuEpo) administration increases vascular nitric oxide (NO) production in healthy rats. We hypothesized that rHuEpo hypertension is associated with increased endothelial expression of nitric oxide synthase and augmented NO-dependent vasodilation. Male rats were instrumented with pulsed Doppler flow probes around their ascending aorta and with arterial and femoral catheters. Rats were treated for 14 days with rHuEpo (2 U/d) or vehicle. rHuEpo elevated hematocrit and increased mean arterial pressure (142 +/- 3 versus 116 +/- 4 mm Hg). Thoracic aorta segments from rHuEpo rats had a modest increase in NO-dependent relaxation assessed by acetylcholine (10(-10) to 10(-5) mol/L) relaxation of phenylephrine (PE) (10(-6) mol/L) contracted arteries. Relaxation to NO-donor, s-nitrosyl acetylpenicillamine, and PE contraction were not different from control arteries. The NO synthase inhibitor, N-omega-nitro-L-arginine, increased blood pressure and total peripheral resistance more in rHuEpo rats at both 10 and 30 mg/kg. NOS expression in rHuEpo aorta and plasma NOx concentrations were increased compared with control. Thus, it appears that vascular eNOS expression is increased and causes basal vasodilation in rHuEpo hypertensive rats.
本研究旨在确定给予重组人促红细胞生成素（rHuEpo）是否会增加健康大鼠血管中一氧化氮（NO）的生成。我们假设rHuEpo所致高血压与一氧化氮合酶的内皮表达增加及NO依赖性血管舒张增强有关。雄性大鼠在其升主动脉周围安装脉冲多普勒血流探头，并插入动脉和股动脉导管。大鼠接受rHuEpo（2 U/d）或赋形剂治疗14天。rHuEpo使血细胞比容升高，并使平均动脉压增加（142±3对116±4 mmHg）。通过乙酰胆碱（10⁻¹⁰至10⁻⁵ mol/L）对去氧肾上腺素（PE）（10⁻⁶ mol/L）收缩动脉的舒张作用评估，rHuEpo大鼠的胸主动脉段NO依赖性舒张有适度增加。对NO供体、S-亚硝基乙酰青霉胺的舒张作用及PE收缩与对照动脉无差异。在10和30 mg/kg剂量下，NO合酶抑制剂N-ω-硝基-L-精氨酸使rHuEpo大鼠的血压和总外周阻力升高更明显。与对照相比，rHuEpo大鼠主动脉中NOS表达及血浆NOx浓度增加。因此，似乎在rHuEpo高血压大鼠中血管内皮型NOS表达增加并导致基础血管舒张。
