Fandrey J, Rob P M, Jelkmann W
Institut für Physiologie, Medizinische Universität zu Lübeck, BRD.
Nephron. 1991;57(1):94-8. doi: 10.1159/000186224.
One serious side effect of ciclosporin (CS) therapy is its acute nephrotoxicity characterized by a marked decrease in glomerular filtration rate (GFR). A main determinant of GFR is the ultrafiltration coefficient which is thought to be regulated by the contractile state of the cells of the mesangium. CS enhances contractions of mesangial cells elicited with angiotensin II. By way of a lowered ultrafiltration coefficient this effect of CS may be partly responsible for its acute nephrotoxicity. We have therefore examined the effect of compounds that may attenuate the enhanced contractile response of the smooth-muscle-like mesangial cells. Prostaglandin E2 (10(-8)-10(-5) mol/l) and dibutyryl cyclic AMP (10(-4) mol/l) reduced the number of contracting cells from more than 50% to about 10%. The clinically used agent theophylline (10(-5) g/ml) decreased the number of contractions of CS-pretreated mesangial cells from 80.0 to 28.4% (p less than 0.001). Additionally, a marked decrease in the percentage of contractions (83.3 to 33.3%; p less than 0.001) was observed when the concentration of magnesium chloride was elevated from 0 to 2 mmol/l. The finding that the enhanced contractile response of CS-pretreated mesangial cells can be overcome by theophylline and/or high magnesium levels may be of clinical interest with a view to acute CS nephrotoxicity.
环孢素（CS）治疗的一个严重副作用是其急性肾毒性，其特征是肾小球滤过率（GFR）显著降低。GFR的一个主要决定因素是超滤系数，人们认为它受系膜细胞收缩状态的调节。CS增强了血管紧张素II引起的系膜细胞收缩。通过降低超滤系数，CS的这种作用可能部分导致了其急性肾毒性。因此，我们研究了可能减弱平滑肌样系膜细胞增强的收缩反应的化合物的作用。前列腺素E2（10^(-8)-10^(-5)mol/L）和二丁酰环磷腺苷（10^(-4)mol/L）将收缩细胞的数量从50%以上减少到约10%。临床使用的药物茶碱（10^(-5)g/ml）使CS预处理的系膜细胞的收缩次数从80.0%降至28.4%（p<0.001）。此外，当氯化镁浓度从0升高到2mmol/L时，观察到收缩百分比显著降低（从83.3%降至33.3%；p<0.001）。从急性CS肾毒性的角度来看，茶碱和/或高镁水平可以克服CS预处理的系膜细胞增强的收缩反应这一发现可能具有临床意义。
