del Castillo D, Raij L, Shultz P J, Tolins J P
Department of Medicine, Veterans Affairs Medical Center, Minneapolis, MN, USA.
Nephrol Dial Transplant. 1995;10(4):505-8. doi: 10.1093/ndt/10.4.505.
In a subset of dialysis patients, erythropoietin (rHuEpo) treatment exacerbates hypertension. The mechanism of this pressor effect is unknown; however, it has been suggested that decreased endogenous nitric oxide (NO) activity may play a role. To explore this hypothesis, Sprague-Dawley rats were given rHuEpo (150 U/kg s.c. three times per week) or corresponding vehicle. Blood pressure, haematocrit, and urinary excretion of the stable NO metabolites, nitrite (NO2) and nitrate (NO3), were determined at baseline and 3 weeks. After 3 weeks of rHuEpo treatment there was a significant increase in blood pressure and haematocrit, while in vehicle-treated rats blood pressure and haematocrit remained at basal levels. Urinary excretion of NO2+NO3 increased compared to basal in rHuEpo, but not vehicle rats. Thus in normal rats rHuEpo does have a significant pressor effect, but this is not associated with decreased activity of the endogenous NO system. Thus decreased endogenous NO activity is not responsible for rHuEpo-associated hypertension. These data further suggest that endogenous NO activity is increased in rHuEpo-treated rats, perhaps as a counter-regulatory mechanism that limits the pressor effect. Whether this mechanism is active in the setting of rHuEpo-treated chronic renal failure in humans is unknown.
在一部分透析患者中，促红细胞生成素（rHuEpo）治疗会加重高血压。这种升压作用的机制尚不清楚；然而，有人认为内源性一氧化氮（NO）活性降低可能起了作用。为了探究这一假设，给Sprague-Dawley大鼠皮下注射rHuEpo（150 U/kg，每周3次）或相应的赋形剂。在基线和3周时测定血压、血细胞比容以及稳定的NO代谢产物亚硝酸盐（NO2）和硝酸盐（NO3）的尿排泄量。rHuEpo治疗3周后，血压和血细胞比容显著升高，而接受赋形剂治疗的大鼠血压和血细胞比容保持在基础水平。与基础水平相比，rHuEpo处理的大鼠尿中NO2+NO3排泄增加，但赋形剂处理的大鼠没有增加。因此，在正常大鼠中，rHuEpo确实有显著的升压作用，但这与内源性NO系统活性降低无关。因此，内源性NO活性降低不是rHuEpo相关高血压的原因。这些数据进一步表明，rHuEpo处理的大鼠内源性NO活性增加，这可能是一种限制升压作用的反调节机制。这种机制在接受rHuEpo治疗的人类慢性肾衰竭患者中是否起作用尚不清楚。
