Asberg A, Berg K J, Hartmann A
Laboratory for Renal Physiology, The National Hospital, Oslo, N-0027, Norway.
Microvasc Res. 2000 Sep;60(2):81-90. doi: 10.1006/mvre.2000.2247.
Both impaired and enhanced microvascular function have been described in humans on cyclosporin A (CsA) therapy. In the present study we investigated the acute microvascular effects of a single CsA administration in renal transplant recipients on maintenance CsA therapy. Fourteen renal transplant recipients, median age 48 years (range 24-63 years), transplanted 4-12 weeks earlier, were included in this placebo-controlled, double-blinded, crossover study. All recipients had stable renal function; median serum creatinine was 116 micromol/L (range 80-184 micromol/L). Immunosuppressive therapy consisted of CsA, prednisolone, and either azathioprine or mycophenolate. Microvascular function was assessed by laser Doppler flowmetry in combination with acetylcholine (endothelium dependent) stimulation and the postocclusive reactive hyperemia test. Measurements were performed before (control) and 2.5 h following administration of CsA (Neoral) or matching placebo and repeated with reversed medication after at least 6 days. Vasodilative responses to acetylcholine stimulation were significantly higher following CsA ingestion compared with placebo. The mean change in AUC(1.5) (area under the flux versus time curve) from control to 2.5 h was 100 +/-145 for CsA and -292 +/- 140 AU x min for placebo (P = 0.047, n = 10). The postocclusive hyperemic response AUC(rh) was also significantly higher following CsA intake (39 +/- 4 AU x min) compared to placebo (30 +/- 4 AU x min) (P = 0.006, n = 12). This study shows that each dose of CsA induces a transient increase in skin microvascular reactivity in renal transplant recipients. We speculate that this might be due to the potentiation of one or several endothelial-dependent compensatory vasodilative mechanisms in the microvascular bed.
在接受环孢素A（CsA）治疗的人类患者中，已观察到微血管功能受损和增强的情况。在本研究中，我们调查了单次给予CsA对接受维持性CsA治疗的肾移植受者微血管的急性影响。14名肾移植受者纳入了这项安慰剂对照、双盲、交叉研究，他们的年龄中位数为48岁（范围24 - 63岁），移植时间在4 - 12周前。所有受者肾功能稳定；血清肌酐中位数为116微摩尔/升（范围80 - 184微摩尔/升）。免疫抑制治疗包括CsA、泼尼松龙以及硫唑嘌呤或霉酚酸酯。通过激光多普勒血流仪结合乙酰胆碱（内皮依赖性）刺激和闭塞后反应性充血试验来评估微血管功能。在给予CsA（新山地明）或匹配的安慰剂之前（对照）和给药后2.5小时进行测量，并在至少6天后更换药物重复测量。与安慰剂相比，摄入CsA后对乙酰胆碱刺激的血管舒张反应显著更高。从对照到2.5小时，CsA组的AUC(1.5)（通量与时间曲线下面积）平均变化为100±145，安慰剂组为 - 292±140 AU·min（P = 0.047，n = 10）。与安慰剂（30±4 AU·min）相比，摄入CsA后闭塞后充血反应AUC(rh)也显著更高（39±4 AU·min）（P = 0.006，n = 12）。本研究表明，每次给予CsA都会导致肾移植受者皮肤微血管反应性短暂增加。我们推测这可能是由于微血管床中一种或几种内皮依赖性代偿性血管舒张机制的增强。
