Yalcin Murat, Ak Fusun, Cangul I Taci, Erturk Melih
Department of Physiology, Faculty of Veterinary Medicine, Uludag University, 16059 Bursa, Turkey.
Auton Neurosci. 2007 Jul 31;134(1-2):1-7. doi: 10.1016/j.autneu.2007.01.005. Epub 2007 Feb 15.
Erythropoietin (EPO) is a hematopoietic factor, which is produced primarily by the adult kidney in response to tissue hypoxia. There is strong evidence that EPO may also be synthesized in the brain and act as a neuroprotector or neuromodulator in the central nervous system. The present study investigated the effect of centrally administered EPO on cardiovascular and respiratory parameters in anaesthetized rats. The animals were anaesthetized with ketamine (70 mg/kg) and xylazine (10 mg/kg) mixture. EPO at doses of 0.06, 0.12, 0.25 and 0.50 IU/5 microl or 0.9% saline as a control were injected intracerebroventricularly and blood pressure, heart rate, respiratory rate, tidal volume and minute ventilation were recorded. Following the administration of EPO, there was a significant increase in blood pressure, heart and respiratory rates, tidal volume and minute ventilation which were time and dose dependant. In order to investigate whether these effects of centrally injected EPO was caused by the diffusion of the drug to the periphery, the highest dose EPO (0.5 IU) in the present study, was injected intravenously but intravenously injected EPO showed no significant effect in these parameters. In conclusion, our findings showed that centrally injected erythropoietin caused pressor and tachycardic response, an increase in respiratory frequency and volume in anaesthetized rats. Moreover intravenous injection of the highest dose of EPO used in the study caused no effect suggesting a central mechanism of action for the agent. Hence, one can hypothesize that erythropoietin may play a role in the central regulation of cardiovascular and respiratory system as a neuromodulator or neuromediator.
促红细胞生成素（EPO）是一种造血因子，主要由成年肾脏在组织缺氧时产生。有强有力的证据表明，EPO也可能在大脑中合成，并在中枢神经系统中作为神经保护剂或神经调节剂发挥作用。本研究调查了向麻醉大鼠脑内注射EPO对心血管和呼吸参数的影响。动物用氯胺酮（70mg/kg）和赛拉嗪（10mg/kg）混合物麻醉。以0.06、0.12、0.25和0.50IU/5微升的剂量或0.9%生理盐水作为对照，将EPO脑室内注射，并记录血压、心率、呼吸频率、潮气量和分钟通气量。注射EPO后，血压、心率和呼吸频率、潮气量和分钟通气量显著增加，且具有时间和剂量依赖性。为了研究脑内注射EPO的这些作用是否是由药物扩散到外周引起的，本研究中最高剂量的EPO（0.5IU）进行静脉注射，但静脉注射EPO在这些参数上没有显著作用。总之，我们的研究结果表明，脑内注射促红细胞生成素会引起麻醉大鼠的升压和心动过速反应，呼吸频率和容量增加。此外，本研究中使用的最高剂量EPO静脉注射没有效果，提示该药物的作用机制为中枢性。因此，可以推测促红细胞生成素可能作为神经调节剂或神经介质在心血管和呼吸系统的中枢调节中发挥作用。
