EFFECT OF TREATMENT OF HEMODIALYSIS-PATIENTS WITH NIFEDIPINE ON METABOLISM AND FUNCTION OF POLYMORPHONUCLEAR
EFFECT OF TREATMENT OF HEMODIALYSIS-PATIENTS WITH NIFEDIPINE ON METABOLISM AND FUNCTION OF POLYMORPHONUCLEAR
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DOI：
10.1016/0272-6386(95)90106-x
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发表时间：
1995-03-01
影响因子：
13.2
通讯作者：
MASSRY, SG
中科院分区：
文献类型：
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作者：
ALEXIEWICZ, JM;SMOGORZEWSKI, M;MASSRY, SG
患有慢性肾衰竭的动物和患者都具有受损的吞噬作用，这最可能是由于细胞溶质钙{[Ca 2 +]i}的基础水平升高和其多形核白细胞（PMNL）的三磷酸腺苷（ATP）含量降低。在患有慢性肾衰竭的动物中，这些紊乱通过用钙通道阻断剂治疗来预防或逆转，本研究检测了11例正常人、18例血液透析患者PMNLs的基础[Ca ~（2+）]i、ATP含量和吞噬功能（其中7人患有糖尿病）和18名接受硝苯地平治疗的血液透析患者未用硝苯地平治疗的血液透析患者外周血PMNLs [Ca ~（2+）]i基础水平显著高于未用硝苯地平治疗的血液透析患者（P <0.05）。（P < 0.01）升高（非糖尿病患者，77 +/- 3.2 nmol/L;糖尿病患者，75 +/- 1.9 nmol/L）与正常值相比（42 ± 0.9 nmol/L），硝苯地平治疗与非糖尿病患者和非糖尿病患者[Ca 2 +]i向正常值的恢复有关。（51 +/- 4.5 nmol/L）和糖尿病（54 +/- 2.5 nmol/L）血液透析患者外周血中性粒细胞ATP含量显著高于正常对照组（P <0.05），P <0.01。（P < 0.01）降低，硝苯地平治疗后ATP含量恢复正常，吞噬作用显著血液透析患者的血尿素氮水平明显降低（P < 0.01）（非糖尿病患者，78 +/- 4.0 μ g油/10（7）PMNLs/min;糖尿病患者，77 +/- 4.8 μ g油/10（7）PMNLs/min），硝苯地平治疗使受损的吞噬功能恢复正常（非糖尿病患者，133 +/- 2.5 μ g油/10（7）PMNLs/min;糖尿病患者，129 ± 6.4微克油/10（7）粒PMNLs/分钟），尽管甲状旁腺激素的血液水平升高，这些数据表明，钙通道阻滞剂干扰甲状旁腺素诱导的血液透析患者PMNL [Ca 2 +]i增加，从而改善其代谢和功能，如果在其他人类细胞中得到证实，这些观察结果将为改善尿毒症的体征和症状提供合理的治疗方法。(C)1995年由国家肾脏基金会，公司。
Both animals and patients with chronic renal failure have impaired phagocytosis, which is most likely due to elevated basal levels of cytosolic calcium {[Ca2+]i} and reduced adenosine triphosphate (ATP) content of their polymorphonuclear leukocytes (PMNLs), In animals with chronic renal failure, these derangements are prevented or reversed by their treatment with a calcium channel blocker, This observation may have important clinical implications if these drugs exert a similar effect in humans with chronic renal failure, We examined the basal levels [Ca2+]i, ATP content, and phagocytosis in PMNLs from 11 normal subjects, 18 hemodialysis patients (seven of whom had diabetes mellitus), and 18 hemodialysis patients treated with nifedipine (eight of whom had diabetes mellitus), The basal levels of the [Ca2+]i content of the PMNLs in hemodialysis patients without nifedipine therapy were significantly (P < 0.01) elevated (nondiabetic patients, 77 +/- 3.2 nmol/L; diabetic patients, 75 +/- 1.9 nmol/L) compared with normal values (42 +/- 0.9 nmol/L), Treatment with nifedipine was associated with the return of [Ca2+]i toward normal values in both the nondiabetic (51 +/- 4.5 nmol/L) and diabetic (54 +/- 2.5 nmol/L) hemodialysis patients, The ATP content of PMNLs from hemodialysis patient was significantly (P < 0.01) reduced compared with normal, and nifedipine therapy restored the ATP content to normal values, Phagocytosis was significantly (P < 0.01) impaired in hemodialysis patients (nondiabetic patients, 78 +/- 4.0 mu g oil/10(7) PMNLs/min; diabetic patients, 77 +/- 4.8 mu g oil/10(7) PMNLs/min), Nifedipine therapy returned the impaired phagocytosis toward normal (nondiabetic patients, 133 +/- 2.5 mu g oil/10(7) PMNLs/min; diabetic patients, 129 +/- 6.4 mu g oil/10(7) PMNLs/min), The effect of nifedipine on the metabolism and function of PMNLs in hemodialysis patients occurred despite the elevated blood levels of parathyroid hormone, These data indicate that the calcium channel blocker interferes with the parathyroid hormone-induced increase in [Ca2+]i of PMNLs from hemodialysis patients and consequently improves their metabolism and function, If confirmed in other human cells, these observations would provide for a rational therapeutic approach to ameliorate the signs and symptoms of uremia. (C) 1995 by the National Kidney Foundation, Inc.