Tojo A, Doumoto M, Oka K, Numabe A, Kimura K, Yagi S
Department of Medicine, Dokkyo University School of Medicine, Tochigi, Japan.
Am J Physiol. 1996 Apr;270(4 Pt 2):R744-8. doi: 10.1152/ajpregu.1996.270.4.R744.
Erythropoietin (EPO) has been reported to induce hypertension in hemodialysis patients with family history of hypertension. In this study, to reveal the mechanism of EPO-induced hypertension, we examined the acute effect of EPO on blood pressure (BP) and renal hemodynamics in genetically hypertensive rats, and we also tested the effect of BQ-123, an endothelin ETA-receptor blocker, on EPO-induced changes in hemodynamics. Male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY), aged 9-12 wk, were anesthetized, and BP was monitored through the carotid artery. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured before and after an intravenous injection of EPO (1,000 U/kg body wt). In another group of SHR, BQ-123 was continuously infused (1.2 mg.kg body wt-1.h-1) during the experiments. The acute injections of EPO increased BP significantly in SHR in a dose-dependent manner, whereas WKY did not show a significant increase in BP after EPO injections. The effect of EPO on BP in SHR was blocked by BQ-123. In SHR, an acute injection of EPO decreased RPF significantly (from 1.78 +/- 0.16 to 1.49 +/- 0.18 ml.min-1.100 g body wt-1, P < 0.05) without a change in GFR, whereas WKY did not show significant changes in either RPF or GFR. The effect of EPO on RPF in SHR was completely blocked by BQ-123 (from 1.92 +/- 0.26 to 1.88 +/- 0.28 ml.min-1.100 g wt-1, NS). EPO caused a significant increase in plasma endothelin ET-1 in SHR (from 2.3 +/- 0.6 to 6.3 +/- 1.6 pg/ml, P < 0.05), but not in WKY. In conclusion, acute administration of EPO raised blood pressure and reduced RPF in SHR, and these vasoconstrictive effects of EPO are mediated via ETA receptors by an enhanced ET-1 release.
据报道，促红细胞生成素（EPO）可使有高血压家族史的血液透析患者发生高血压。在本研究中，为揭示EPO诱导高血压的机制，我们检测了EPO对遗传性高血压大鼠血压（BP）和肾脏血流动力学的急性影响，并且我们还测试了内皮素ETA受体阻滞剂BQ-123对EPO诱导的血流动力学变化的影响。将9至12周龄的雄性自发性高血压大鼠（SHR）和血压正常的Wistar-Kyoto大鼠（WKY）麻醉，并通过颈动脉监测血压。在静脉注射EPO（1000 U/kg体重）前后测量肾血浆流量（RPF）和肾小球滤过率（GFR）。在另一组SHR中，实验期间持续输注BQ-123（1.2 mg·kg体重-1·h-1）。急性注射EPO使SHR的血压以剂量依赖性方式显著升高，而WKY在注射EPO后血压未显著升高。SHR中EPO对血压的影响被BQ-123阻断。在SHR中，急性注射EPO使RPF显著降低（从1.78±0.16降至1.49±0.18 ml·min-1·100 g体重-1，P<0.05），而GFR无变化，而WKY的RPF和GFR均未显示出显著变化。SHR中EPO对RPF的影响被BQ-123完全阻断（从1.92±0.26升至1.88±0.28 ml·min-1·100 g体重-1，无显著性差异）。EPO使SHR的血浆内皮素ET-1显著升高（从2.3±0.6升至6.3±1.6 pg/ml，P<0.05），但WKY未出现这种情况。总之，急性给予EPO可使SHR血压升高并降低RPF，且EPO的这些血管收缩作用是通过ETA受体由增强的ET-1释放介导的。
