Valentin J P, Ribstein J, Jover B, Cristol J P, Mimran A
Service de médecine interne, hôpital Lapeyronie, CHU, Montpellier.
Arch Mal Coeur Vaiss. 1990 Jul;83(8):1291-4.
Chronic treatment with dihydropyridines and to a lesser extent other calcium antagonists often cause peripheral edema without fluid retention. To test the possibility that calcium antagonists affect extracellular fluid partition between plasma and interstitium, we compared the effects of a benzothiazepine derivate diltiazem, a dihydropyridine derivate nicardipine and vehicle in binephrectomized anesthetized rats by measuring changes in hematocrit and plasma protein concentration. Forty minutes infusion of low dose of nicardipine and diltiazem (0.1 and 10 micrograms/kg/min respectively) had no significant effect on blood pressure (-2 +/- 2 and -4 +/- 3% respectively); nicardipine increased hematocrit by 5.6 +/- 0.5% (p less than 0.05); while diltiazem had no significant effect as compared to the vehicle (+1.5 +/- 0.3 and +1.5 +/- 0.3% respectively). The calculated loss of plasma volume during nicardipine infusion was 9.2 +/- 0.8% as compared to 2.5 +/- 0.6% and 2.7 +/- 0.6% in rats receiving diltiazem and vehicle respectively. Infusion of higher doses of nicardipine and diltiazem (1 and 100 micrograms/kg/min respectively) decreased blood pressure by 21 +/- 2 and 19 +/- 2% while the changes in hematocrit were not different than those observed with with the lower doses (5.5 +/- 0.6 and 1.4 +/- 0.3% respectively). To document and localize an alteration in vascular leak of proteins induced by the drugs, albumin-bound Evans Blue (EB) extravasation was measured spectrophotometrically in different tissues after extraction by formamide. Nicardipine but not diltiazem increased vascular permeation of EB-albumin in skeletal and cardiac muscle. No change was observed in brain, liver, spleen as compared to rats receiving the vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)
长期使用二氢吡啶类药物，在较小程度上使用其他钙拮抗剂，常常会导致外周水肿但无液体潴留。为了检验钙拮抗剂是否会影响血浆与间质之间细胞外液的分配，我们通过测量血细胞比容和血浆蛋白浓度的变化，比较了苯并硫氮䓬衍生物地尔硫䓬、二氢吡啶衍生物尼卡地平以及赋形剂对双肾切除麻醉大鼠的影响。低剂量的尼卡地平和地尔硫䓬（分别为0.1和10微克/千克/分钟）输注40分钟对血压无显著影响（分别为-2±2%和-4±3%）；尼卡地平使血细胞比容增加了5.6±0.5%（p＜0.05）；而与赋形剂相比，地尔硫䓬无显著影响（分别为+1.5±0.3%和+1.5±0.3%）。与分别接受地尔硫䓬和赋形剂的大鼠相比，输注尼卡地平期间计算得出的血浆容量损失为9.2±0.8%，而地尔硫䓬组和赋形剂组分别为2.5±0.6%和2.7±0.6%。输注更高剂量的尼卡地平和地尔硫䓬（分别为1和100微克/千克/分钟）使血压降低了21±2%和19±2%，而血细胞比容的变化与低剂量时观察到的变化无差异（分别为5.5±0.6%和1.4±0.3%）。为了记录和定位药物引起的蛋白质血管渗漏改变，在通过甲酰胺提取后，用分光光度法测量不同组织中与白蛋白结合的伊文思蓝（EB）外渗情况。尼卡地平而非地尔硫䓬增加了骨骼肌和心肌中EB - 白蛋白的血管通透性。与接受赋形剂的大鼠相比，脑、肝、脾未见变化。（摘要截取自250字）
